Phototherapy via Modulation of β-Amyloid in Combating Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is one of the most prevalent forms of neurodegenerative disease. Although some controversy exists, β-amyloid peptide (Aβ) is recognized to play an essential role in the pathophysiology of AD. The Aβ species are known to exist in various forms, including soluble monomers, oligomers, and insoluble aggregates. Despite extensive efforts to regulate Aβ aggregation, no successful medications have been developed to date. Among the various strategies for AD treatment, phototherapy, including photodynamic therapy (PDT), photothermal therapy (PTT), photopharmacology, and photobiomodulation (PBM) have attracted increased attention because of the spatiotemporal controllability. Representative examples of PDT, PTT, photopharmacology, and PBM are discussed in terms of inhibitory mechanism, the unique properties of materials, and the design of phototherapy modulators. The major challenges of phototherapy against AD are addressed and the promising prospects are proposed. It is concluded that the noninvasive light-assisted approaches will become a promising strategy for intensifying the modulation of Aβ aggregation or promoting Aβ clearance and thus facilitating AD treatment.

Keywords

Alzheimer's disease / phototherapy / β-amyloid

References

[1] W. K. Self and D. M. Holtzman, “Emerging Diagnostics and Therapeutics for Alzheimer Disease,” Nature Medicine 29, no. 9 (2023): 2187-2199, https://doi.org/10.1038/s41591-023-02505-2.

[2] E. Karran and B. De Strooper, “The Amyloid Hypothesis in Alzheimer Disease: New Insights From New Therapeutics,” Nature Reviews Drug Discovery 21, no. 4 (2022): 306-318, https://doi.org/10.1038/s41573-022-00391-w.

[3] P. Scheltens, B. De Strooper, M. Kivipelto, et al., “Alzheimer's Disease,” Lancet 397, no. 10284 (2021): 1577-1590, https://doi.org/10.1016/S0140-6736(20)32205-4.

[4] I. W. Hamley, “The Amyloid Beta Peptide: A Chemist's Perspective. Role in Alzheimer's and Fibrillization,” Chemical Reviews 112, no. 10 (2012): 5147-5192, https://doi.org/10.1021/cr3000994.

[5] E. J. Fernandez-Perez, B. Muñoz, D. A. Bascuñan, et al., “Synaptic Dysregulation and Hyperexcitability Induced by Intracellular Amyloid Beta Oligomers,” Aging Cell 20, no. 11 (2021): e13495, https://doi.org/10.1111/acel.13495.

[6] X. Yang, G. Meisl, B. Frohm, E. Thulin, T. P. J. Knowles, and S. Linse, “On the Role of Sidechain Size and Charge in the Aggregation of Aβ42 With Familial Mutations,” Proceedings National Academy of Science USA 115, no. 26 (2018): E5849-E5858, https://doi.org/10.1073/pnas.1803539115.

[7] S. Linse, “Monomer-Dependent Secondary Nucleation in Amyloid Formation,” Biophysical Reviews 9, no. 4 (2017): 329-338, https://doi.org/10.1007/s12551-017-0289-z.

[8] P. N. Nirmalraj, S. Bhattacharya, and D. Thompson, “Accelerated Alzheimer's Aβ-42 Secondary Nucleation Chronologically Visualized on Fibril Surfaces,” Science Advances 10, no. 43 (2024): eadp5059, https://doi.org/10.1126/sciadv.adp5059.

[9] P. E. Cramer, J. R. Cirrito, D. W. Wesson, et al., “ApoE-Directed Therapeutics Rapidly Clear β-amyloid and Reverse Deficits in AD Mouse Models,” Science 335, no. 6075 (2012): 1503-1506, https://doi.org/10.1126/science.1217697.

[10] A. R. Ladiwala, J. S. Dordick, and P. M. Tessier, “Aromatic Small Molecules Remodel Toxic Soluble Oligomers of Amyloid Beta Through Three Independent Pathways,” Journal of Biological Chemistry 286, no. 5 (2011): 3209-3218, https://doi.org/10.1074/jbc.M110.173856.

[11] K. Ono, K. Hasegawa, H. Naiki, and M. Yamada, “Curcumin Has Potent Anti-Amyloidogenic Effects for Alzheimer's Beta-Amyloid Fibrils in Vitro,” Journal of Neuroscience Research 75, no. 6 (2004): 742-750, https://doi.org/10.1002/jnr.20025.

[12] Q. I. Churches, J. Caine, K. Cavanagh, et al., “Naturally Occurring Polyphenolic Inhibitors of Amyloid Beta Aggregation,” Bioorganic & Medicinal Chemistry Letters 24, no. 14 (2014): 3108-3112, https://doi.org/10.1016/j.bmcl.2014.05.008.

[13] T. C. Pham, V. N. Nguyen, Y. Choi, S. Lee, and J. Yoon, “Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy,” Chemical Reviews 121, no. 21 (2021): 13454-13619, https://doi.org/10.1021/acs.chemrev.1c00381.

[14] J. Karges, “Clinical Development of Metal Complexes as Photosensitizers for Photodynamic Therapy of Cancer,” Angewandte Chemie International Edition 61, no. 5 (2022): e202112236, https://doi.org/10.1002/anie.202112236.

[15] H. S. Jung, P. Verwilst, A. Sharma, J. Shin, J. L. Sessler, and J. S. Kim, “Organic Molecule-Based Photothermal Agents: An Expanding Photothermal Therapy Universe,” Chemical Society Reviews 47, no. 7 (2018): 2280-2297, https://doi.org/10.1039/c7cs00522a.

[16] J. Qi, A. S. Amrutha, S. Ishida-Ishihara, et al., “Caging Bioactive Triarylimidazoles: An Approach to Create Visible Light-Activatable Drugs,” Journal of the American Chemical Society 146, no. 26 (2024): 18002-18010, https://doi.org/10.1021/jacs.4c04468.

[17] Z. Wan, P. Zhang, L. Lv, and Y. Zhou, “NIR Light-Assisted Phototherapies for Bone-Related Diseases and Bone Tissue Regeneration: A Systematic Review,” Theranostics 10, no. 25 (2020): 11837-11861, https://doi.org/10.7150/thno.49784.

[18] Y. Jiang, Z. Zeng, J. Yao, et al., “Treatment of Alzheimer's Disease With Small-Molecule Photosensitizers,” Chinese Chemical Letters 34 (2023): 107966, https://doi.org/10.1016/j.cclet.2022.107966.

[19] D. Huang, W. Liao, J. Li, et al., “Alzheimer's disease: Status of Low-Dimensional Nanotherapeutic Materials,” Advanced Functional Materials 34 (2024): 2302015, https://doi.org/10.1002/adfm.202302015.

[20] F. Zeng, K. Peng, L. Han, and J. Yang, “Photothermal and Photodynamic Therapies via NIR-Activated Nanoagents in Combating Alzheimer's Disease,” ACS Biomaterials Science & Engineering 7, no. 8 (2021): 3573-3585, https://doi.org/10.1021/acsbiomaterials.1c00605.

[21] D. A. Rodríguez-Soacha and M. Decker, “Photopharmacology in Alzheimer's Disease,” Advanced Therapeutics 1 (2018): 1800037, https://doi.org/10.1002/adtp.201800037.

[22] J. C. Rojas, A. K. Bruchey, and F Gonzalez-Lima, “Low-Level Light Therapy Improves Cortical Metabolic Capacity and Memory Retention.” Journal of Alzheimer's Disease 2012; 32(3): 741-752, https://doi.org/10.3233/JAD-2012-120817.

[23] F. Tian, S. N. Hase, F. Gonzalez-Lima, and H. Liu, “Transcranial Laser Stimulation Improves human Cerebral Oxygenation,” Laser Surgery and Medicine 48, no. 4 (2016): 343-349, https://doi.org/10.1002/lsm.22471.

[24] H. Nawashiro, K. Wada, K. Nakai, and S. Sato, “Focal Increase in Cerebral Blood Flow After Treatment With near-Infrared Light to the Forehead in a Patient in a Persistent Vegetative state,” Photomedicine and Laser Surgery 30, no. 4 (2012): 231-233, https://doi.org/10.1089/pho.2011.3044.

[25] Y. Lu, R. Wang, Y. Dong, et al., “Low-Level Laser Therapy for Beta Amyloid Toxicity in Rat Hippocampus,” Neurobiology of Aging 49 (2017): 165-182, https://doi.org/10.1016/j.neurobiolaging.2016.10.003.

[26] M. C. DeRosa and R. J. Crutchley, “Photosensitized Singlet Oxygen and Its Applications,” Coordination Chemistry Reviews 233 (2002): 351-371, https://doi.org/10.1016/S0010-8545(02)00034-6.

[27] S. Hao, J. Wu, Y. Huang, and J. Lin, “Natural Dyes as Photosensitizers for Dye-Sensitized Solar Cell,” Solar Energy 80, no. 2 (2006): 209-214, https://doi.org/10.1016/j.solener.2005.05.009.

[28] J. Gao, Y. Tian, Y. Li, F. Hu, and W. Wu, “Design Strategies for Aggregation-Induced Emission Photosensitizers With Enhanced Safety in Photodynamic Therapy,” Coordination Chemistry Reviews 507 (2024): 215756, https://doi.org/10.1016/j.ccr.2024.215756.

[29] I. Tomizawa, H. Nakagawa, Y. Sohma, M. Kanai, Y. Hori, and T. Tomita, “Photo-Oxygenation as a New Therapeutic Strategy for Neurodegenerative Proteinopathies by Enhancing the Clearance of Amyloid Proteins,” Frontiers in Aging Neuroscience 14 (2022): 945017, https://doi.org/10.3389/fnagi.2022.945017.

[30] S. Liu, Y. Li, J. Yang, L. Zhang, and J. Yan, “An in Situ-Activated and Chemi-Excited Photooxygenation System Based on G-poly(thioacetal) for Aβ1-42 Aggregates,” Journal of Materials Chemistry B 12, no. 42 (2024): 10850-10860, https://doi.org/10.1039/d4tb01147c.

[31] N. Nagashima, S. Ozawa, M. Furuta, et al., “Catalytic Photooxygenation Degrades Brain Aβ in Vivo,” Science Advances 7, no. 13 (2021): eabc9750, https://doi.org/10.1126/sciadv.abc9750.

[32] V. N. Nguyen, Z. Zhao, B. Z. Tang, and J. Yoon, “Organic Photosensitizers for Antimicrobial Phototherapy,” Chemical Society Reviews 51, no. 9 (2022): 3324-3340, https://doi.org/10.1039/d1cs00647a.

[33] H. Yagi, D. Ozawa, K. Sakurai, et al., “Laser-Induced Propagation and Destruction of Amyloid Beta Fibrils,” Journal of Biological Chemistry 285, no. 25 (2010): 19660-19667, https://doi.org/10.1074/jbc.M109.076505.

[34] P. Bjorkman, M. Saper, B. Samraoui, et al., “Structure of the human Class I Histocompatibility Antigen, HLA-A2,” Nature 329 (1987): 506-512, https://doi.org/10.1038/329506a0.

[35] A. Taniguchi, Y. Shimizu, K. Oisaki, Y. Sohma, and M. Kanai, “Switchable Photooxygenation Catalysts That Sense Higher-Order Amyloid Structures,” Nature Chemistry 8, no. 10 (2016): 974-982, https://doi.org/10.1038/nchem.2550.

[36] H. Wu, Z. Liu, Y. Shao, et al., “Degradation of Amyloid Peptide Aggregates by Targeted Singlet Oxygen Delivery From a Benzothiazole Functionalized Naphthalene Endoperoxide,” Chemical Communications 58, no. 23 (2022): 3747-3750, https://doi.org/10.1039/d1cc07133e.

[37] Y. Cao, J. Liu, C. Hu, Y. Li, X. Wang, and J. Yan, “N-Methylbenzothiazolium Based Theranostics as Fluorescence Imaging and Photo-oxidation Agents for Amyloid-β,” Sensors & Actuators, B: Chemical 414 (2024): 135932, https://doi.org/10.1016/j.snb.2024.135932.

[38] Z. Du, D. Yu, X. Du, P. Scott, J. Ren, and X. Qu, “Self-Triggered Click Reaction in an Alzheimer's Disease Model: In Situ Bifunctional Drug Synthesis Catalyzed by Neurotoxic Copper Accumulated in Amyloid-β Plaques,” Chemical Science 10, no. 44 (2019): 10343-10350, https://doi.org/10.1039/c9sc04387j.

[39] Y. Guo, C. Xia, Y. Cao, et al., “Modulation of Intramolecular Freedom for Tuning Fluorescence Imaging and Photooxidation of Amyloid-β Aggregates,” Materials Horizons 11, no. 23 (2024): 6040-6048, https://doi.org/10.1039/d4mh00660g.

[40] B. Wang, J. Shi, N. Guo, et al., “Rational Design Synthesis and Evaluation of a Novel Near-Infrared Fluorescent Probe for Selective Imaging of Amyloid-β Aggregates in Alzheimer's Disease,” Analytica Chimica Acta 1281 (2023): 341900, https://doi.org/10.1016/j.aca.2023.341900.

[41] J. Yang, X. Wang, J. Liu, et al., “Near-Infrared Photooxygenation Theranostics Used for the Specific Mapping and Modulating of Amyloid-β Aggregation,” Analytical Chemistry 94, no. 45 (2022): 15902-15907, https://doi.org/10.1021/acs.analchem.2c04042.

[42] H. Tan, K. Zhou, J. Yan, et al., “Dual-Functional Red-Emitting Fluorescent Probes for Imaging Beta-amyloid Plaques and Viscosity,” Sensors & Actuators, B: Chemical 298 (2019): 126903, https://doi.org/10.1016/j.snb.2019.126903.

[43] K. Zhou, H. Bai, L. Feng, J. Dai, and M. Cui, “Smart D-π-A Type Near-Infrared Aβ Probes: Effects of a Marked π Bridge on Optical and Biological Properties,” Analytical Chemistry 89, no. 17 (2017): 9432-9437, https://doi.org/10.1021/acs.analchem.7b02246.

[44] H. Fu, M. Cui, L. Zhao, et al., “Highly Sensitive Near-Infrared Fluorophores for in Vivo Detection of Amyloid-β Plaques in Alzheimer's Disease,” Journal of Medicinal Chemistry 58, no. 17 (2015): 6972-6983, https://doi.org/10.1021/acs.jmedchem.5b00861.

[45] H. Liu, Y. Li, L. Wei, Z. Ye, J. Yuan, and L. Xiao, “Amyloid-β Aggregates-Restricted Rotational Motion Amplifies Photo-Catalytic Activity From Quinolinium Derivatives,” Nano Today 58 (2024): 102434, https://doi.org/10.1016/j.nantod.2024.102434.

[46] Z. Xie, C. Hu, Y. Li, L. Zhang, and J. Yan, “Optimization of Quinolinium-Carbazole Theranostics for the Improved Photooxidation of β-amyloid Aggregates With the Variation of Conjugation Site,” Journal Photochem Photobio A: Chemical 456 (2024): 115823, https://doi.org/10.1016/j.jphotochem.2024.115823.

[47] C. Ran, X. Xu, S. B. Raymond, et al., “Design, Synthesis, and Testing of Difluoroboron-Derivatized Curcumins as near-infrared Probes for in Vivo Detection of Amyloid-Beta Deposits,” Journal of the American Chemical Society 131, no. 42 (2009): 15257-15261, https://doi.org/10.1021/ja9047043.

[48] J. Ni, A. Taniguchi, S. Ozawa, et al., “Near-Infrared Photoactivatable Oxygenation Catalysts of Amyloid Peptide,” Chem 4, no. 4 (2018): 807-820, https://doi.org/10.1016/j.chempr.2018.02.008.

[49] S. Kuang, B. Zhu, J. Zhang, et al., “A Photolabile Curcumin-Diazirine Analogue Enables Phototherapy With Physically and Molecularly Produced Light for Alzheimer's disease Treatment,” Angewandte Chemie International Edition 62, no. 45 (2023): e202312519, https://doi.org/10.1002/anie.202312519.

[50] T. Yogo, Y. Urano, Y. Ishitsuka, F. Maniwa, and T. Nagano, “Highly Efficient and Photostable Photosensitizer Based on BODIPY Chromophore,” Journal of the American Chemical Society 127, no. 35 (2005): 12162-12163, https://doi.org/10.1021/ja0528533.

[51] A. Kamkaew, S. H. Lim, H. B. Lee, L. V. Kiew, L. Y. Chung, and K. Burgess, “BODIPY Dyes in Photodynamic Therapy,” Chemical Society Reviews 42, no. 1 (2013): 77-88, https://doi.org/10.1039/c2cs35216h.

[52] M. Ono, H. Watanabe, H. Kimura, and H. Saji, “BODIPY-Based Molecular Probe for Imaging of Cerebral β-amyloid Plaques,” ACS Chemical Neuroscience 3, no. 4 (2012): 319-324, https://doi.org/10.1021/cn3000058.

[53] S. Lim, M. M. Haque, D. Su, et al., “Development of a BODIPY-Based Fluorescent Probe for Imaging Pathological Tau Aggregates in Live Cells,” Chemical Communications 53, no. 10 (2017): 1607-1610, https://doi.org/10.1039/c6cc08826k.

[54] P. Verwilst, H. R. Kim, J. Seo, et al., “Rational Design of in Vivo Tau Tangle-Selective Near-Infrared Fluorophores: Expanding the BODIPY Universe,” Journal of the American Chemical Society 139, no. 38 (2017): 13393-13403, https://doi.org/10.1021/jacs.7b05878.

[55] T. Suzuki, Y. Hori, T. Sawazaki, et al., “Photo-Oxygenation Inhibits Tau Amyloid Formation,” Chemical Communications 55, no. 44 (2019): 6165-6168, https://doi.org/10.1039/c9cc01728c.

[56] S. Ozawa, Y. Hori, Y. Shimizu, et al., “Photo-Oxygenation by a Biocompatible Catalyst Reduces Amyloid-β Levels in Alzheimer's disease Mice,” Brain 144, no. 6 (2021): 1884-1897, https://doi.org/10.1093/brain/awab058.

[57] T. Chatterjee, A. Srinivasan, M. Ravikanth, and T. K. Chandrashekar, “Smaragdyrins and Sapphyrins Analogues,” Chemical Reviews 117, no. 4 (2017): 3329-3376, https://doi.org/10.1021/acs.chemrev.6b00507.

[58] D. Fan, D. Wang, T. Han, and B. Tang, “Fused Heterocyclic Polymers With Aggregation-Induced Emission: Synthesis and Applications,” ACS Applied Polymer Materials 4, no. 5 (2022): 3120-3130, https://doi.org/10.1021/acsapm.1c01476.

[59] M. Ono, M. Haratake, H. Saji, and M. Nakayama, “Development of Novel Beta-Amyloid Probes Based on 3,5-diphenyl-1,2,4-Oxadiazole,” Bioorganic & Medicinal Chemistry 16 (2008): 6867-6872, A9693.

[60] M. R. Mangione, A. Palumbo Piccionello, C. Marino, et al., “Photo-Inhibition of Aβ Fibrillation Mediated by a Newly Designed Fluorinated Oxadiazole,” RSC Advances 5 (2015): 16540-16548, https://doi.org/10.1039/c4ra13556c.

[61] G. Bitan, A. Lomakin, and D. B. Teplow, “Amyloid Beta-Protein Oligomerization: Prenucleation Interactions Revealed by Photo-Induced Cross-Linking of Unmodified Proteins,” Journal of Biological Chemistry 276, no. 37 (2001): 35176-35184, https://doi.org/10.1074/jbc.M102223200.

[62] G. Anwar, Y. Cao, W. J. Shi, L. Niu, and J. W. Yan, “Rational Design, Synthesis, and Evaluation of Rofecoxib-Based Photosensitizers for the NIR Imaging and Photo-oxidization of Aβ Aggregates,” ACS Chemical Neuroscience 15, no. 22 (2024): 4202-4209, https://doi.org/10.1021/acschemneuro.4c00496.

[63] A. Taniguchi, D. Sasaki, A. Shiohara, et al., “Attenuation of the Aggregation and Neurotoxicity of Amyloid-β Peptides by Catalytic Photooxygenation,” Angewandte Chemie International Edition 53, no. 5 (2014): 1382-1385, https://doi.org/10.1002/anie.201308001.

[64] R. Cibulka, R. Vasold, and B. König, “Catalytic Photooxidation of 4-Methoxybenzyl Alcohol With a Flavin-zinc(II)-Cyclen Complex,” Chemistry European Journal 10, no. 24 (2004): 6224-6231, https://doi.org/10.1002/chem.200400232.

[65] J. S. Lee, B. I. Lee, and C. B. Park, “Photo-Induced Inhibition of Alzheimer's β-amyloid Aggregation in Vitro by Rose Bengal,” Biomaterials 38 (2015): 43-49, https://doi.org/10.1016/j.biomaterials.2014.10.058.

[66] W. Atsumi, K. Kawabata, and M. Yamane, et al., “Rose Bengal Promoted Catalytic Amyloid-β Oxygenation by Sonoactivation,” Synlett 35, no. 08 (2024): 920-924, https://doi.org/10.1055/a-2182-7614.

[67] V. Paban, C. Manrique, M. Filali, S. Maunoir-Regimbal, F. Fauvelle, and B. Alescio-Lautier, “Therapeutic and Preventive Effects of Methylene Blue on Alzheimer's Disease Pathology in a Transgenic Mouse Model,” Neuropharmacology 76 (2014): 68-79, https://doi.org/10.1016/j.neuropharm.2013.06.033.

[68] E. M. Sontag, G. P. Lotz, N. Agrawal, et al., “Methylene Blue Modulates Huntingtin Aggregation Intermediates and Is Protective in Huntington's disease Models,” Journal of Neuroscience 32, no. 32 (2012): 11109-11119, https://doi.org/10.1523/JNEUROSCI.0895-12.2012.

[69] M. Necula, L. Breydo, S. Milton, et al., “Methylene Blue Inhibits Amyloid Abeta Oligomerization by Promoting Fibrillization,” Biochemistry 46, no. 30 (2007): 8850-8860, https://doi.org/10.1021/bi700411k.

[70] C. M. Wischik, P. Bentham, D. J Wischik., and K. M. Seng, “O3-04-07: Tau Aggregation Inhibitor (TAI) Therapy With rember™ Arrests Disease Progression in Mild and Moderate Alzheimer's Disease Over 50 Weeks,” Alzheimer's Dement 4 (2008): 167, https://doi.org/10.1016/j.jalz.2008.05.438.

[71] B. I. Lee, Y. S. Suh, Y. J. Chung, K. Yu, and C. B. Park, “Shedding Light on Alzheimer's β-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-assembly of β-amyloid Peptides and Disintegrates Their Aggregates,” Scientific Reports 7, no. 1 (2017): 7523, https://doi.org/10.1038/s41598-017-07581-2.

[72] M. A. Rajora, J. W. H. Lou, and G. Zheng, “Advancing Porphyrin's Biomedical Utility via Supramolecular Chemistry,” Chemical Society Reviews 46, no. 21 (2017): 6433-6469, https://doi.org/10.1039/c7cs00525c.

[73] D. Kessel, “Photodynamic Therapy: From the Beginning,” Photodiagnosis and Photodynamic Therapy 1, no. 1 (2004): 3-7, https://doi.org/10.1016/S1572-1000(04)00003-1.

[74] A. Hirabayashi, Y. Shindo, K. Oka, D. Takahashi, and K. Toshima, “Photodegradation of Amyloid β and Reduction of Its Cytotoxicity to PC12 Cells Using Porphyrin Derivatives,” Chemical Communications 50, no. 67 (2014): 9543-9546, https://doi.org/10.1039/c4cc03791j.

[75] B. I. Lee, S. Lee, Y. S. Suh, et al., “Photoexcited Porphyrins as a Strong Suppressor of β-amyloid Aggregation and Synaptic Toxicity,” Angewandte Chemie International Edition 54, no. 39 (2015): 11472-11476, https://doi.org/10.1002/anie.201504310.

[76] Q. Zhan, X. Shi, T. Wang, et al., “Design and Synthesis of Thymine Modified Phthalocyanine for Aβ Protofibrils Photodegradation and Aβ Peptide Aggregation Inhibition,” Talanta 191 (2019): 27-38, https://doi.org/10.1016/j.talanta.2018.08.037.

[77] G. A. Kostenich, I. N. Zhuravkin, and E. A. Zhavrid, “Experimental Grounds for Using chlorin e6 in the Photodynamic Therapy of Malignant Tumors,” Journal of Photochemistry and Photobiology B Biology 22, no. 3 (1994): 211-217, https://doi.org/10.1016/1011-1344(93)06974-8.

[78] H. Mojzisova, S. Bonneau, P. Maillard, K. Berg, and D. Brault, “Photosensitizing Properties of Chlorins in Solution and in Membrane-Mimicking Systems,” Photochemical & Photobiological Sciences 8, no. 6 (2009): 778-787, https://doi.org/10.1039/b822269j.

[79] G. Leshem, M. Richman, E. Lisniansky, et al., “Photoactive Chlorin e6 Is a Multifunctional Modulator of Amyloid-β Aggregation and Toxicity via Specific Interactions With Its Histidine Residues,” Chemical Science 10, no. 1 (2018): 208-217, https://doi.org/10.1039/c8sc01992d.

[80] H. Kroto, J. Heath, S. O'Brien, et al., “C60: Buckminsterfullerene,” Nature 318 (1985): 162-163, https://doi.org/10.1038/318162a0.

[81] J. Shi, L. Wang, J. Gao, et al., “A Fullerene-Based Multi-Functional Nanoplatform for Cancer Theranostic Applications,” Biomaterials 35, no. 22 (2014): 5771-5784, https://doi.org/10.1016/j.biomaterials.2014.03.071.

[82] B. I. Lee, Y. J. Chung, and C. B. Park, “Photosensitizing Materials and Platforms for Light-Triggered Modulation of Alzheimer's β-amyloid Self-Assembly,” Biomaterials 190-191 (2019): 121-132, https://doi.org/10.1016/j.biomaterials.2018.10.043.

[83] Y. Ishida, S. Tanimoto, D. Takahashi, and K. Toshima, “Photo-Degradation of Amyloid β by a Designed Fullerene-Sugar Hybrid,” Medicinal Chemistry Communications 1 (2010): 212-215, https://doi.org/10.1039/C0MD00075B.

[84] Y. Ishida, T. Fujii, K. Oka, D. Takahashi, and K. Toshima, “Inhibition of Amyloid β Aggregation and Cytotoxicity by Photodegradation Using a Designed Fullerene Derivative,” Chemistry - An Asian Journal 6, no. 9 (2011): 2312-2315, https://doi.org/10.1002/asia.201100421.

[85] Z. Du, N. Gao, X. Wang, J. Ren, and X. Qu, “Near-Infrared Switchable Fullerene-Based Synergy Therapy for Alzheimer's Disease,” Small 14, no. 33 (2018): e1801852, https://doi.org/10.1002/smll.201801852.

[86] M. Gon, K. Tanaka, and Y. Chujo, “A Highly Efficient Near-Infrared-Emissive Copolymer With a N=N Double-Bond π-Conjugated System Based on a Fused Azobenzene-Boron Complex,” Angewandte Chemie International Edition 57, no. 22 (2018): 6546-6551, https://doi.org/10.1002/anie.201803013.

[87] J. Rautio, H. Kumpulainen, T. Heimbach, et al., “Prodrugs: Design and Clinical Applications,” Nature Reviews Drug Discovery 7, no. 3 (2008): 255-270, https://doi.org/10.1038/nrd2468.

[88] M. Kanai and Y. Takeuchi, “Catalysis Medicine: Participating in the Chemical Networks of Living Organisms Through Catalysts,” Tetrahedron 131 (2023): 133227, https://doi.org/10.1016/j.tet.2022.133227.

[89] M. Furuta, S. Arii, H. Umeda, et al., “Leuco Ethyl Violet as Self-Activating Prodrug Photocatalyst for in Vivo Amyloid-Selective Oxygenation,” Advanced Science 11, no. 26 (2024): e2401346, https://doi.org/10.1002/advs.202401346.

[90] N. Tomar, A. Agrawal, V. Singh Dhaka, and P. K. Surolia, “Ruthenium Complexes Based Dye Sensitized Solar Cells: Fundamentals and Research Trends,” Solar Energy 207 (2020): 59-76, https://doi.org/10.1016/j.solener.2020.06.060.

[91] M. Parasram and V. Gevorgyan, “Visible Light-Induced Transition Metal-catalyzed Transformations: Beyond Conventional Photosensitizers,” Chemical Society Reviews 46, no. 20 (2017): 6227-6240, https://doi.org/10.1039/c7cs00226b.

[92] M. H. Lee, E. J. Kim, H. Lee, et al., “Liposomal Texaphyrin Theranostics for Metastatic Liver Cancer,” Journal of the American Chemical Society 138, no. 50 (2016): 16380-16387, https://doi.org/10.1021/jacs.6b09713.

[93] Y. Wu, S. Li, Y. Chen, W. He, and Z. Guo, “Recent Advances in Noble Metal Complex Based Photodynamic Therapy,” Chemical Science 13, no. 18 (2022): 5085-5106, https://doi.org/10.1039/d1sc05478c.

[94] C. Imberti, P. Zhang, H. Huang, and P. J. Sadler, “New Designs for Phototherapeutic Transition Metal Complexes,” Angewandte Chemie International Edition 59, no. 1 (2020): 61-73, https://doi.org/10.1002/anie.201905171.

[95] A. Aliyan, B. Kirby, C. Pennington, and A. A. Martí, “Unprecedented Dual Light-Switching Response of a Metal Dipyridophenazine Complex Toward Amyloid-β Aggregation,” Journal of the American Chemical Society 138, no. 28 (2016): 8686-8689, https://doi.org/10.1021/jacs.6b04411.

[96] A. Aliyan, et al., “Photochemical Identification of Molecular Binding Sites on the Surface of Amyloid-β Fibrillar Aggregates,” Chem 3, no. 5 (2017): 898-912, https://doi.org/10.1016/j.chempr.2017.09.011.

[97] G. Son, B. I. Lee, Y. J. Chung, and C. B. Park, “Light-Triggered Dissociation of Self-assembled β-amyloid Aggregates Into Small, Nontoxic Fragments by Ruthenium (II) Complex,” Acta Biomaterialia 67 (2018): 147-155, https://doi.org/10.1016/j.actbio.2017.11.048.

[98] N. P. Cook, M. Ozbil, C. Katsampes, R. Prabhakar, and A. A. Martí, “Unraveling the Photoluminescence Response of Light-Switching Ruthenium(II) Complexes Bound to Amyloid-β,” Journal of the American Chemical Society 135, no. 29 (2013): 10810-10816, https://doi.org/10.1021/ja404850u.

[99] B. Jiang, A. Aliyan, N. P. Cook, et al., “Monitoring the Formation of Amyloid Oligomers Using Photoluminescence Anisotropy,” Journal of the American Chemical Society 141, no. 39 (2019): 15605-15610, https://doi.org/10.1021/jacs.9b06966.

[100] A. Aliyan, N. P. Cook, and A. A. Martí, “Interrogating Amyloid Aggregates Using Fluorescent Probes,” Chemical Reviews 119, no. 23 (2019): 11819-11856, https://doi.org/10.1021/acs.chemrev.9b00404.

[101] D. E. Silva, M. P. Cali, W. M. Pazin, et al., “Luminescent Ru(II) Phenanthroline Complexes as a Probe for Real-Time Imaging of Aβ Self-Aggregation and Therapeutic Applications in Alzheimer's Disease,” Journal of Medicinal Chemistry 59, no. 19 (2016): 9215-9227, https://doi.org/10.1021/acs.jmedchem.6b01130.

[102] N. A. Vyas, S. S. Bhat, A. S. Kumbhar, et al., “Ruthenium(II) Polypyridyl Complex as Inhibitor of Acetylcholinesterase and Aβ Aggregation,” European Journal of Medicinal Chemistry 75 (2014): 375-381, https://doi.org/10.1016/j.ejmech.2014.01.052.

[103] J. C. Bataglioli, L. M. F. Gomes, C. Maunoir, et al., “Modification of Amyloid-Beta Peptide Aggregation via Photoactivation of Strained Ru(ii) Polypyridyl Complexes,” Chemical Science 12, no. 21 (2021): 7510-7520, https://doi.org/10.1039/d1sc00004g.

[104] D. A. Fancy, C. Denison, K. Kim, et al., “Scope, Limitations and Mechanistic Aspects of the Photo-Induced Cross-Linking of Proteins by Water-Soluble Metal Complexes,” Chemistry & Biology 7, no. 9 (2000): 697-708, https://doi.org/10.1016/s1074-5521(00)00020-x.

[105] F. Amini, C. Denison, H. J. Lin, L. Kuo, and T. Kodadek, “Using Oxidative Crosslinking and Proximity Labeling to Quantitatively Characterize Protein-Protein and Protein-Peptide Complexes,” Chemistry & Biology 10, no. 11 (2003): 1115-1127, https://doi.org/10.1016/j.chembiol.2003.11.001.

[106] S. Meunier, E. Strable, and M. G. Finn, “Crosslinking of and Coupling to Viral Capsid Proteins by Tyrosine Oxidation,” Chemistry & Biology 11, no. 3 (2004): 319-326, https://doi.org/10.1016/j.chembiol.2004.02.019.

[107] J. Kang, S. J. Lee, J. S. Nam, et al., “An Iridium(III) Complex as a Photoactivatable Tool for Oxidation of Amyloidogenic Peptides With Subsequent Modulation of Peptide Aggregation,” Chemistry - A European Journal 23, no. 7 (2017): 1645-1653, https://doi.org/10.1002/chem.201604751.

[108] J. Kang, J. S. Nam, H. J. Lee, et al., “Chemical Strategies to Modify Amyloidogenic Peptides Using Iridium(iii) Complexes: Coordination and Photo-Induced Oxidation,” Chemical Science 10, no. 28 (2019): 6855-6862, https://doi.org/10.1039/c9sc00931k.

[109] M. Kim, G. Gupta, J. Lee, et al., “Metal-BODIPY Complexes: Versatile Photosensitizers for Oxidizing Amyloid-β Peptides and Modulating Their Aggregation Profiles,” Inorganic Chemistry Frontiers 11 (2024): 966-1977, https://doi.org/10.1039/D3QI02445H.

[110] Z. Yang, D. Wang, C. Zhang, et al., “The Applications of Gold Nanoparticles in the Diagnosis and Treatment of Gastrointestinal Cancer,” Frontiers in Oncology 11 (2022): 819329, https://doi.org/10.3389/fonc.2021.819329.

[111] W. Zhu, R. Michalsky, Ö. Metin, et al., “Monodisperse Au Nanoparticles for Selective Electrocatalytic Reduction of CO2 to CO,” Journal of the American Chemical Society 135, no. 45 (2013): 16833-16836, https://doi.org/10.1021/ja409445p.

[112] G. B. Silveira, A. P. Muller, R. A. Machado-de-Ávila, and P. C. L. Silveira, “Advance in the Use of Gold Nanoparticles in the Treatment of Neurodegenerative Diseases: New Perspectives,” Neural Regeneration Research 16, no. 12 (2021): 2425-2426, https://doi.org/10.4103/1673-5374.313040.

[113] W. Liu, H. Zhang, X. Dong, and Y. Sun, “Composite of Gold Nanoclusters and Basified Human Serum Albumin Significantly Boosts the Inhibition of Alzheimer's β-amyloid by Photo-Oxygenation,” Acta Biomaterialia 144 (2022): 157-167, https://doi.org/10.1016/j.actbio.2022.03.019.

[114] K. Ge, Y. Mu, M. Liu, et al., “Gold Nanorods With Spatial Separation of CeO₂ Deposition for Plasmonic-Enhanced Antioxidant Stress and Photothermal Therapy of Alzheimer's Disease,” ACS Applied Materials & Interface 14, no. 3 (2022): 3662-3674, https://doi.org/10.1021/acsami.1c17861.

[115] X. Di, Z. Pei, Y. Pei, and T. D. James, “Tumor Microenvironment-Oriented MOFs for Chemodynamic Therapy,” Coordination Chemistry Reviews 484 (2023): 215098, https://doi.org/10.1016/j.ccr.2023.215098.

[116] M. X. Wu and Y. W. Yang, “Metal-Organic Framework (MOF)-Based Drug/Cargo Delivery and Cancer Therapy,” Advanced Materials 29, no. 23 (2017),

[117] M. Lismont, L. Dreesen, and S. Wuttke, “Metal-Organic Framework Nanoparticles in Photodynamic Therapy: Current Status and Perspectives,” Advanced Functional Materials 27 (2017): 1606314, https://doi.org/10.1002/adfm.201606314.

[118] M. Ma, N. Gao, Y. Sun, J. Ren, and X. Qu, “A Near-Infrared Responsive Drug Sequential Release System for Better Eradicating Amyloid Aggregates,” Small 13, no. 46 (2017), https://doi.org/10.1002/smll.201701817.

[119] J. Zheng, Z. Lin, G. Lin, H. Yang, and L. Zhang, “Preparation of Magnetic Metal-Organic Framework Nanocomposites for Highly Specific Separation of Histidine-Rich Proteins,” Journal of Materials Chemistry B 3, no. 10 (2015): 2185-2191, https://doi.org/10.1039/c4tb02007c.

[120] J. Wang, Y. Fan, Y. Tan, et al., “Porphyrinic Metal-Organic Framework PCN-224 Nanoparticles for Near-Infrared-Induced Attenuation of Aggregation and Neurotoxicity of Alzheimer's Amyloid-β Peptide,” ACS Applied Materials & Interface 10, no. 43 (2018): 36615-36621, https://doi.org/10.1021/acsami.8b15452.

[121] D. Yu, Y. Guan, F. Bai, et al., “Metal-Organic Frameworks Harness Cu Chelating and Photooxidation Against Amyloid β Aggregation in Vivo,” Chemistry - A European Journal 25, no. 14 (2019): 3489-3495, https://doi.org/10.1002/chem.201805835.

[122] J. Wang, Y. Gu, X. Liu, et al., “Near-Infrared Photothermally Enhanced Photo-Oxygenation for Inhibition of Amyloid-β Aggregation Based on RVG-Conjugated Porphyrinic Metal-Organic Framework and Indocyanine Green Nanoplatform,” International Journal of Molecular Sciences 23, no. 18 (2022): 10885, https://doi.org/10.3390/ijms231810885.

[123] W. C. Luo, L. N. Bao, Y. Zhang, et al., “A Ru³⁺-Functionalized-NMOF Nanozyme as an Inhibitor and Disaggregator of β-amyloid Aggregates,” Journal of Materials Chemistry B 12 (2024): 12239-12250, https://doi.org/10.1039/d4tb01313a.

[124] N. Gao, Z. Du, Y. Guan, K. Dong, J. Ren, and X. Qu, “Chirality-Selected Chemical Modulation of Amyloid Aggregation,” Journal of the American Chemical Society 141, no. 17 (2019): 6915-6921, https://doi.org/10.1021/jacs.8b12537.

[125] W. Liu, X. Dong, and Y. Sun, “d-Enantiomeric RTHLVFFARK-NH2: A Potent Multifunctional Decapeptide Inhibiting Cu²⁺-Mediated Amyloid β-Protein Aggregation and Remodeling Cu²⁺-Mediated Amyloid β Aggregates,” ACS Chemical Neuroscience 10, no. 3 (2019): 1390-1401, https://doi.org/10.1021/acschemneuro.8b00440.

[126] H. Zhang, C. Hao, A. Qu, et al., “Light-Induced Chiral Iron Copper Selenide Nanoparticles Prevent β-Amyloidopathy in Vivo,” Angewandte Chemie International Edition 59, no. 18 (2020): 7131-7138, https://doi.org/10.1002/anie.202002028.

[127] M. Li, C. Xu, J. Ren, E. Wang, and X. Qu, “Photodegradation of β-Sheet Amyloid Fibrils Associated With Alzheimer's Disease by Using Polyoxometalates as Photocatalysts,” Chemical Communications 49, no. 97 (2013): 11394-11396, https://doi.org/10.1039/c3cc46772d.

[128] N. Gao, H. Sun, K. Dong, et al., “Transition-Metal-Substituted Polyoxometalate Derivatives as Functional Anti-Amyloid Agents for Alzheimer's Disease,” Nature Communications 5 (2014): 3422, https://doi.org/10.1038/ncomms4422.

[129] Y. J. Chung, K. Kim, B. I. Lee, and C. B. Park, “Carbon Nanodot-sensitized Modulation of Alzheimer's β-amyloid Self-Assembly, Disassembly, and Toxicity,” Small 13, no. 34 (2017), https://doi.org/10.1002/smll.201700983.

[130] C. Yan, C. Wang, X. Shao, et al., “Multifunctional Carbon-dot-photosensitizer Nanoassemblies for Inhibiting Amyloid Aggregates, Suppressing Microbial Infection, and Overcoming the Blood-Brain Barrier,” ACS Applied Materials & Interface 14, no. 42 (2022): 47432-47444, https://doi.org/10.1021/acsami.2c14118.

[131] X. Lin, H. Zhang, W. Liu, X. Dong, and Y. Sun, “Methylene Blue-Doped Carbonized Polymer Dots: A Potent Photooxygenation Scavenger Targeting Alzheimer's β-amyloid,” ACS Applied Materials & Interface 15, no. 37 (2023): 44062-44074, https://doi.org/10.1021/acsami.3c06948.

[132] X. Lin, X. Dong, and Y. Sun, “Dual-Carbon Dots Composite: A Multifunctional Photo-propelled Nanomotor Against Alzheimer's β-amyloid,” Small 11 (2024): e2407154, https://doi.org/10.1002/smll.202407154.

[133] M. Zhang, X. Mao, Y. Yu, C. X. Wang, Y. L. Yang, and C. Wang, “Nanomaterials for Reducing Amyloid Cytotoxicity,” Advanced Materials 25, no. 28 (2013): 3780-3801, https://doi.org/10.1002/adma.201301210.

[134] L. Feng, C. Zhu, H. Yuan, L. Liu, F. Lv, and S. Wang, “Conjugated Polymer Nanoparticles: Preparation, Properties, Functionalization and Biological Applications,” Chemical Society Reviews 42, no. 16 (2013): 6620-6633, https://doi.org/10.1039/c3cs60036j.

[135] Z. Wang, X. Dong, and Y. Sun, “Hydrophobic Modification of Carboxyl-Terminated Polyamidoamine Dendrimer Surface Creates a Potent Inhibitor of Amyloid-β Fibrillation,” Langmuir 34, no. 47 (2018): 14419-14427, https://doi.org/10.1021/acs.langmuir.8b02890.

[136] G. Zhao, X. Dong, and Y. Sun, “Self-Assembled Curcumin-poly(carboxybetaine methacrylate) Conjugates: Potent Nano-Inhibitors Against Amyloid β-Protein Fibrillogenesis and Cytotoxicity,” Langmuir 35, no. 5 (2019): 1846-1857, https://doi.org/10.1021/acs.langmuir.8b01921.

[137] H. Yang, X. Li, L. Zhu, et al., “Heat Shock Protein Inspired Nanochaperones Restore Amyloid-β Homeostasis for Preventative Therapy of Alzheimer's Disease,” Advanced, Science 6, no. 22 (2019): 1901844, https://doi.org/10.1002/advs.201901844.

[138] J. Zhang, J. Liu, Y. Zhu, et al., “Photodynamic Micelles for Amyloid β Degradation and Aggregation Inhibition,” Chemical Communications 52, no. 81 (2016): 12044-12047, https://doi.org/10.1039/c6cc06175c.

[139] Z. Liu, M. Ma, D. Yu, J. Ren, and X. Qu, “Target-Driven Supramolecular Self-Assembly for Selective Amyloid-β Photooxygenation Against Alzheimer's Disease,” Chemical Science 11, no. 40 (2020): 11003-11008, https://doi.org/10.1039/d0sc04984k.

[140] S. Naghibi, T. Chen, A. Jamshidi Ghahfarokhi, and Y. Tang, “AIEgen-Enhanced Protein Imaging: Probe Design and Sensingmechanisms,” Aggregate 2 (2021): e41, https://doi.org/10.1002/agt2.41.

[141] Z. Zhuang, J. Li, P. Shen, Z. Zhao, and B. Z. Tang, “Exploring and Leveraging Aggregation Effects on Reactive Oxygen Species Generation in Photodynamic Therapy,” Aggregate 5 (2024): e540, https://doi.org/10.1002/agt2.540.

[142] J. Li, Z. Zhuang, X. Lou, Z. Zhao, and B. Z. Tang, “Molecular Design and Biomedical Application of AIEgens With Photochemical Activity,” Chemical & Biomedical Imaging 1 (2023): 785-795, https://doi.org/10.1021/cbmi.3c00038.

[143] Y. Hong, J. W. Lam, and B. Z. Tang, “Aggregation-Induced Emission,” Chemical Society Reviews 40, no. 11 (2011): 5361-5388, https://doi.org/10.1039/c1cs15113d.

[144] J. Qi, H. Ou, Q. Liu, and D. Ding, “Gathering Brings Strength: How Organic Aggregates Boost Disease Phototheranostics,” Aggregate 2 (2021): 95-113, https://doi.org/10.1002/agt2.25.

[145] L. Liu, W. Liu, Y. Sun, and X. Dong, “Design of Aggregation-Induced Emission-Active Fluorogen-Based Nanoparticles for Imaging and Scavenging Alzheimer's β-amyloid by Photo-Oxygenation,” Journal of Materials Chemistry B 11, no. 37 (2023): 8994-9004, https://doi.org/10.1039/d3tb01134h.

[146] P. L. Donabedian, T. K. Pham, D. G. Whitten, and E. Y. Chi, “Oligo(p-phenylene ethynylene) Electrolytes: A Novel Molecular Scaffold for Optical Tracking of Amyloids,” Acs Chemical Neuroscience 6, no. 9 (2015): 1526-1535, https://doi.org/10.1021/acschemneuro.5b00086.

[147] P. L. Donabedian, M. Evanoff, F. A. Monge, D. G. Whitten, and E. Y. Chi, “Substituent, Charge, and Size Effects on the Fluorogenic Performance of Amyloid Ligands: A Small-Library Screening Study,” ACS Omega 2, no. 7 (2017): 3192-3200, https://doi.org/10.1021/acsomega.7b00231.

[148] A. M. Fanni, F. A. Monge, C. Y. Lin, et al., “High Selectivity and Sensitivity of Oligomeric p-phenylene Ethynylenes for Detecting Fibrillar and Prefibrillar Amyloid Protein Aggregates,” ACS Chemical Neuroscience 10, no. 3 (2019): 1813-1825, https://doi.org/10.1021/acschemneuro.8b00719.

[149] D. G. Whitten, Y. Tang, Z. Zhou, et al., “A Retrospective: 10 Years of Oligo(Phenylene-Ethynylene) Electrolytes: Demystifying Nanomaterials,” Langmuir 35, no. 2 (2019): 307-325, https://doi.org/10.1021/acs.langmuir.8b01810.

[150] A. M. Fanni, D. Okoye, F. A. Monge, et al., “Controlled and Selective Photo-Oxidation of Amyloid-β Fibrils by Oligomeric p-phenylene Ethynylenes,” ACS Applied Materials & Interface 14, no. 13 (2022): 14871-14886, https://doi.org/10.1021/acsami.1c22869.

[151] J. Jeon, B. Yoon, S. H. Song, et al., “Chemiluminescence Resonance Energy Transfer-Based Immunostimulatory Nanoparticles for Sonoimmunotherapy,” Biomaterials 283 (2022): 121466, https://doi.org/10.1016/j.biomaterials.2022.121466.

[152] S. Hosaka, T. Itagaki, and Y. Kuramitsu, “Selectivity and Sensitivity in the Measurement of Reactive Oxygen Species (ROS) Using Chemiluminescent Microspheres Prepared by the Binding of Acridinium Ester or ABEI to Polymer Microspheres,” Luminescence 14, no. 6 (1999): 349-354, https://doi.org/10.1002/(SICI)1522-7243(199911/12)14:6<349::AID-BIO560>3.0.CO;2-6.

[153] M. Yang, J. Huang, J. Fan, J. Du, K. Pu, and X. Peng, “Chemiluminescence for Bioimaging and Therapeutics: Recent Advances and Challenges,” Chemical Society Reviews 49, no. 19 (2020): 6800-6815, https://doi.org/10.1039/d0cs00348d.

[154] J. Yang, W. Chi, W. J. Shi, L. Zhang, and J. Yan, “An in Situ-Triggered and Chemi-Excited Photooxygenation System for Aβ Aggregates,” Chemical Engineering Journal 456 (2023): 140998, https://doi.org/10.1016/j.cej.2022.140998.

[155] S. Liu, J. Yang, and J. Yan, “Chemiexcitation-Triggered Photosensitizer Activation for Photooxidation of Aβ1-42 Aggregates,” ACS Applied Materials & Interface 16, no. 32 (2024): 41843-41854, https://doi.org/10.1021/acsami.4c06901.

[156] S. Mohanty and A. M. Kaczmarek, “Unravelling the Benefits of Transition-metal-co-doping in Lanthanide Up-Conversion Nanoparticles,” Chemical Society Reviews 51, no. 16 (2022): 6893-6908, https://doi.org/10.1039/d2cs00495j.

[157] W. Zhang, W. Zheng, P. Huang, D. Yang, Z. Shao, and X. Chen, “The Marriage of Perovskite Nanocrystals With Lanthanide-Doped up-conversion Nanoparticles for Advanced Optoelectronic Applications,” Aggregate 5 (2024): e558, https://doi.org/10.1002/agt2.558.

[158] S. Kuk, B. I. Lee, J. S. Lee, and C. B. Park, “Rattle-structured Upconversion Nanoparticles for near-IR-induced Suppression of Alzheimer's β-amyloid Aggregation,” Small 13, no. 11 (2017), https://doi.org/10.1002/smll.201603139.

[159] Z. Zhang, J. Wang, Y. Song, Z. Wang, M. Dong, and L. Liu, “Disassembly of Alzheimer's Amyloid Fibrils by Functional Upconversion Nanoparticles Under Near-Infrared Light Irradiation,” Colloids and Surfaces. B, Biointerfaces 181 (2019): 341-348, https://doi.org/10.1016/j.colsurfb.2019.05.053.

[160] Y. Guan, W. Cao, T. Li, et al., “NIR-Excited Upconversion Nanoparticles Used for Targeted Inhibition of Aβ42 Monomers and Disassembly of Aβ42 Fibrils,” Journal of Materials Chemistry B 11, no. 7 (2023): 1445-1455, https://doi.org/10.1039/d2tb02104h.

[161] X. Wang, W. Zhang, L. Hou, et al., “A Biomimetic Upconversion Nanobait-Based Near Infrared Light Guided Photodynamic Therapy Alleviates Alzheimer's Disease by Inhibiting β-amyloid Aggregation,” Advanced Healthcare Materials 13, no. 9 (2024): e2303278, https://doi.org/10.1002/adhm.202303278.

[162] J. Xie, Y. Wang, W. Choi, et al., “Overcoming Barriers in Photodynamic Therapy Harnessing Nano-Formulation Strategies,” Chemical Society Reviews 50, no. 16 (2021): 9152-9201, https://doi.org/10.1039/d0cs01370f.

[163] Y M. Wang M. Qiu E. Won, et al., “Emerging 2D Material-Based Nanocarrier for Cancer Therapy Beyond Graphene,” Coordination Chemistry Reviews 400 (2019): 213041, https://doi.org/10.1016/j.ccr.2019.213041.

[164] Y. Xu, Y. Wang, J. An, et al., “2D-Ultrathin MXene/DOXjade Platform for Iron Chelation Chemo-Photothermal Therapy,” Bioactive Materials 14 (2021): 76-85, https://doi.org/10.1016/j.bioactmat.2021.12.011.

[165] W. Chen, J. Ouyang, X. Yi, et al., “Black Phosphorus Nanosheets as a Neuroprotective Nanomedicine for Neurodegenerative Disorder Therapy,” Advanced Materials 30, no. 3 (2018), https://doi.org/10.1002/adma.201703458.

[166] Y. Zhu, Y. Liu, Z. Xie, et al., “Magnetic Black Phosphorus Microbubbles for Targeted Tumor Theranostics,” Nanophotonics 10, no. 12 (2021): 3339-3358, https://doi.org/10.1515/nanoph-2021-0085.

[167] Y. Li, Z. Du, X. Liu, et al., “Near-Infrared Activated Black Phosphorus as a Nontoxic Photo-Oxidant for Alzheimer's Amyloid-β Peptide,” Small 15, no. 24 (2019): e1901116, https://doi.org/10.1002/smll.201901116.

[168] Y. Sun, S. Fan, S. Fan, et al., “In Vitro and in Vivo Toxicity of Black Phosphorus Nanosheets,” Journal of Nanoscience and Nanotechnology 20, no. 2 (2020): 659-667, https://doi.org/10.1166/jnn.2020.16922.

[169] X. Liang, Y. Wang, J. Song, D. Xia, Q. Li, and M. Dong, “Nontoxic Silicene Photothermal Agents With High Near-Infrared Absorption for Disassembly of Alzheimer's Amyloid‑β Fibrils,” Colloids and Surfaces. B, Biointerfaces 216 (2022): 112575, https://doi.org/10.1016/j.colsurfb.2022.112575.

[170] Q. Huang, L. Hao, R. Zhou, B. Zhu, H. Zhao, and X. Cai, “Synthesis, Characterization, and Biological Study of Carboxyl- and Amino-Rich G-C₃N₄ Nanosheets by Different Processing Routes,” Journal of Biomedical Nanotechnology 14, no. 12 (2018): 2114-2123, https://doi.org/10.1166/jbn.2018.2652.

[171] Y. Cao, R. Wu, Y. Zhou, D. Jiang, and W. Zhu, “A Bioinspired Photocatalysis and Electrochemiluminescence Scaffold for Simultaneous Degradation and in Situ Evaluation,” Advanced Functional Materials 32 (2022): 2203005, https://doi.org/10.1002/adfm.202203005.

[172] Y. Zhang, S. Sun, Y. Wu, and F. Chen, “Emerging Roles of Graphitic Carbon Nitride-Based Materials in Biomedical Applications,” ACS Biomaterials Science & Engineering 10, no. 8 (2024): 4645-4661, https://doi.org/10.1021/acsbiomaterials.4c00053.

[173] Y. J. Chung, B. I. Lee, J. W. Ko, and C. B. Park, “Photoactive G-C₃N₄ Nanosheets for Light-Induced Suppression of Alzheimer's β-amyloid Aggregation and Toxicity,” Advanced Healthcare Materials 5, no. 13 (2016): 1560-1565, https://doi.org/10.1002/adhm.201500964.

[174] M. Li, Y. Guan, Z. Chen, et al., “Platinum-Coordinated Graphitic Carbon Nitride Nanosheet Used for Targeted Inhibition of Amyloid β-Peptide Aggregation,” Nano Research 9 (2016): 2411-2423, https://doi.org/10.1007/s12274-016-1127-5.

[175] J. Wang, Y. Feng, X. Tian, C. Li, and L. Liu, “Disassembling and Degradation of Amyloid Protein Aggregates Based on Gold Nanoparticle-Modified G-C₃N₄,” Colloids and Surfaces. B, Biointerfaces 192 (2020): 111051, https://doi.org/10.1016/j.colsurfb.2020.111051.

[176] H. Zhao, R. Ding, X. Zhao, et al., “Graphene-Based Nanomaterials for Drug and/or Gene Delivery, Bioimaging, and Tissue Engineering,” Drug Discovery Today 22, no. 9 (2017): 1302-1317, https://doi.org/10.1016/j.drudis.2017.04.002.

[177] J. Wang, Z. Zhang, H. Zhang, et al., “Enhanced Photoresponsive Graphene Oxide-modified G-C₃N₄ for Disassembly of Amyloid β Fibrils,” ACS Applied Materials & Interface 11, no. 1 (2019): 96-103, https://doi.org/10.1021/acsami.8b10343.

[178] Y. Liu, P. Bhattarai, Z. Dai, and X. Chen, “Photothermal Therapy and Photoacoustic Imaging via Nanotheranostics in Fighting Cancer,” Chemical Society Reviews 48, no. 7 (2019): 2053-2108, https://doi.org/10.1039/c8cs00618k.

[179] C. Xu and K. Pu, “Second Near-Infrared Photothermal Materials for Combinational Nanotheranostics,” Chemical Society Reviews 50, no. 2 (2021): 1111-1137, https://doi.org/10.1039/d0cs00664e.

[180] A. Naskar and K. S. Kim, “Friends Against the Foe: Synergistic Photothermal and Photodynamic Therapy Against Bacterial Infections,” Pharmaceutics 15, no. 4 (2023): 1116, https://doi.org/10.3390/pharmaceutics15041116.

[181] Y. Lai, Y. Zhu, Z. Xu, et al., “Engineering Versatile Nanoparticles for near-infrared Light-Tunable Drug Release and Photothermal Degradation of Amyloid β,” Advanced Functional Materials 30 (2020): 1908473, https://doi.org/10.1002/adfm.201908473.

[182] B. Li, N. Li, L. Chen, et al., “Alleviating Neuroinflammation Through Photothermal Conjugated Polymer Nanoparticles by Regulating Reactive Oxygen Species and Ca²⁺ Signaling,” ACS Applied Materials & Interface 14, no. 43 (2022): 48416-48425, https://doi.org/10.1021/acsami.2c13322.

[183] H. Geng, Y.-C. Pan, R. Zhang, et al., “Binding to Amyloid-β Protein by Photothermal Blood-Brain Barrier-Penetrating Nanoparticles for Inhibition and Disaggregation of Fibrillation,” Advanced Functional Materials 31 (2021): 2102953, https://doi.org/10.1002/adfm.202102953.

[184] Z. Zhang, M. Lv, Y. Liu, J. Qin, Z. Fan, and J. Du, “A Peptide-Polyphenol Coated Polypyrrole Nanoparticle for Synergetic Attenuation of Aggregation and Cytotoxicity of Amyloid-β Fibrils,” Advanced Functional Materials 34 (2024): 2401208, https://doi.org/10.1002/adfm.202401208.

[185] L. Chen, Z. Zhou, Y. Zhang, J. Pan, K. Wang, and H. X. Wang, “Near-Infrared Irradiation Controlled Thermo-switchable Polymeric Photosensitizer Against β-amyloid Fibrillation,” Journal of Materials Chemistry B 10, no. 25 (2022): 4832-4839, https://doi.org/10.1039/d2tb00372d.

[186] A. K. Srivastava and S. Karmakar, “Near-Infrared Responsive Dopamine/Melatonin-Derived Nanocomposites Abrogating in Situ Amyloid β Nucleation, Propagation, and Ameliorate Neuronal Functions,” ACS Applied Materials & Interface 12, no. 5 (2020): 5658-5670, https://doi.org/10.1021/acsami.9b22214.

[187] H. Liu, C. Li, Y. Qian, et al., “Magnetic-Induced Graphene Quantum Dots for Imaging-guided Photothermal Therapy in the Second Near-Infrared Window,” Biomaterials 232 (2020): 119700, https://doi.org/10.1016/j.biomaterials.2019.119700.

[188] B. Geng, W. Shen, F. Fang, et al., “Enriched Graphitic N Dopants of Carbon Dots as F Cores Mediate Photothermal Conversion in the NIR-II Window With High Efficiency,” Carbon 162 (2020): 220-233, https://doi.org/10.1016/j.carbon.2020.02.053.

[189] S. Liao, W. Yue, S. Cai, et al., “Improvement of Gold Nanorods in Photothermal Therapy: Recent Progress and Perspective,” Frontiers in Pharmacology 2021; 12: 664123, https://doi.org/10.3389/fphar.2021.664123.

[190] M. Li, Y. Guan, A. Zhao, J. Ren, and X. Qu, “Using Multifunctional Peptide Conjugated Au Nanorods for Monitoring β-amyloid Aggregation and Chemo-Photothermal Treatment of Alzheimer's Disease,” Theranostics 7, no. 12 (2017): 2996-3006, https://doi.org/10.7150/thno.18459.

[191] D. Liu, W. Li, X. Jiang, et al., “Using Near-Infrared Enhanced Thermozyme and scFv Dual-conjugated Au Nanorods for Detection and Targeted Photothermal Treatment of Alzheimer's Disease,” Theranostics 9, no. 8 (2019): 2268-2281, https://doi.org/10.7150/thno.30649.

[192] X. Wang, Q. Han, X. Liu, C. Wang, and R. Yang, “Multifunctional Inhibitors of β-amyloid Aggregation Based on MoS2/AuNR Nanocomposites With High Near-Infrared Absorption,” Nanoscale 11, no. 18 (2019): 9185-9193, https://doi.org/10.1039/c9nr01845j.

[193] C. Zhang, W. Bu, D. Ni, et al., “A Polyoxometalate Cluster Paradigm With Self-Adaptive Electronic Structure for Acidity/Reducibility-Specific Photothermal Conversion,” Journal of the American Chemical Society 138, no. 26 (2016): 8156-8164, https://doi.org/10.1021/jacs.6b03375.

[194] M. Ma, N. Gao, Y. Sun, X. Du, J. Ren, and X. Qu, “Redox-Activated Near-Infrared-Responsive Polyoxometalates Used for Photothermal Treatment of Alzheimer's Disease,” Advanced Healthcare Materials 7, no. 20 (2018): e1800320, https://doi.org/10.1002/adhm.201800320.

[195] C. Du, W. Feng, X. Dai, et al., “Cu²⁺ -Chelatable and ROS-Scavenging MXenzyme as NIR-II-Triggered Blood-brain Barrier-Crossing Nanocatalyst Against Alzheimer's Disease,” Small 18, no. 39 (2022): e2203031, https://doi.org/10.1002/smll.202203031.

[196] X. Song, Q. Ding, W. Wei, et al., “Peptide-Functionalized Prussian Blue Nanomaterial for Antioxidant Stress and NIR Photothermal Therapy Against Alzheimer's Disease,” Small 19, no. 41 (2023): e2206959, https://doi.org/10.1002/smll.202206959.

[197] P. Ye, L. Li, X. Qi, M. Chi, J. Liu, and M. Xie, “Macrophage Membrane-Encapsulated Nitrogen-Doped Carbon Quantum Dot Nanosystem for Targeted Treatment of Alzheimer's Disease: Regulating Metal Ion Homeostasis and Photothermal Removal of β-amyloid,” Journal of Colloid & Interface Science 650 (2023): 1749-1761, https://doi.org/10.1016/j.jcis.2023.07.132.

[198] K. Ge, Z. Li, A. Wang, et al., “An NIR-Driven Upconversion/C3N4/CoP Photocatalyst for Efficient Hydrogen Production by Inhibiting Electron-hole Pair Recombination for Alzheimer's Disease Therapy,” ACS Nano 17, no. 3 (2023): 2222-2234, https://doi.org/10.1021/acsnano.2c08499.

[199] G. Hartley, “The Cis-Form of Azobenzene,” Nature 140 (1937): 281, https://doi.org/10.1038/140281a0.

[200] A. C. Hamill and C. T. Lee, “Photocontrol of Beta-Amyloid Peptide (1-40) Fibril Growth in the Presence of a Photosurfactant,” Journal of Physical Chemistry B 113, no. 17 (2009): 6164-6172, https://doi.org/10.1021/jp8080113.

[201] T. M. Doran, E. A. Anderson, S. E. Latchney, L. A. Opanashuk, and B. L. Nilsson, “An Azobenzene Photoswitch Sheds Light on Turn Nucleation in Amyloid-β Self-Assembly,” ACS Chemical Neuroscience 3, no. 3 (2012): 211-220, https://doi.org/10.1021/cn2001188.

[202] C. Qian, J. Chen, C. Wang, Q. Wang, X. Wang, and X. Wang, “Light-Controlled Molecular Tweezers Capture Specific Amyloid Oligomers,” Aggregate 5 (2024): e463, https://doi.org/10.1002/agt2.463.

[203] H. Kim, M. J. Kim, Y. W. Kwon, et al., “Benefits of a Skull-Interfaced Flexible and Implantable Multilight Emitting Diode Array for Photobiomodulation in Ischemic Stroke,” Advanced Science 9, no. 11 (2022): e2104629, https://doi.org/10.1002/advs.202104629.

[204] S. G. Disner, C. G. Beevers, and F. Gonzalez-Lima, “Transcranial Laser Stimulation as Neuroenhancement for Attention Bias Modification in Adults With Elevated Depression Symptoms,” Brain Stimulation 9, no. 5 (2016): 780-787, https://doi.org/10.1016/j.brs.2016.05.009.

[205] G. R. Pigatto, C. S. Silva, and N. A. Parizotto, “Photobiomodulation Therapy Reduces Acute Pain and Inflammation in Mice,” Journal of Photochemistry and Photobiology B Biology 196 (2019): 111513, https://doi.org/10.1016/j.jphotobiol.2019.111513.

[206] D. Zhang, Q. Shen, X. Wu, and D. Xing, “Photobiomodulation Therapy Ameliorates Glutamatergic Dysfunction in Mice With Chronic Unpredictable Mild Stress-Induced Depression,” Oxidative Medicine and Cellular Longevity 2021 (2021): 6678276, https://doi.org/10.1155/2021/6678276.

[207] S. G. Oxana, S. Alexander, B. Inna, et al., “Mechanisms of Phototherapy of Alzheimer's Disease During Sleep and Wakefulness: The Role of the Meningeal Lymphatics,” Frontiers of Optoelectronics 16, no. 1 (2023): 22, https://doi.org/10.1007/s12200-023-00080-5.

[208] G. M. Cho, S. Y. Lee, J. H. Park, et al., “Photobiomodulation Using a Low-Level Light-Emitting Diode Improves Cognitive Dysfunction in the 5XFAD Mouse Model of Alzheimer's Disease,” Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 75, no. 4 (2020): 631-639, https://doi.org/10.1093/gerona/gly240.

[209] L. Yang, H. Youngblood, C. Wu, and Q. Zhang, “Mitochondria as a Target for Neuroprotection: Role of Methylene Blue and Photobiomodulation,” Translational Neurodegeneration 9, no. 1 (2020): 19, https://doi.org/10.1186/s40035-020-00197-z.

[210] C. Dompe, L. Moncrieff, J. Matys, et al., “Photobiomodulation-Underlying Mechanism and Clinical Applications,” Journal of Clinical Medicine 9, no. 6 (2020): 1724, https://doi.org/10.3390/jcm9061724.

[211] H. Iaccarino, A. Singer, A. Martorell, et al., “Gamma Frequency Entrainment Attenuates Amyloid Load and Modifies Microglia,” Nature 540 (2016): 230-235, https://doi.org/10.1038/nature20587.

[212] Z. Zhang, Q. Shen, X. Wu, D. Zhang, and D. Xing, “Activation of PKA/SIRT1 Signaling Pathway by Photobiomodulation Therapy Reduces Aβ Levels in Alzheimer's Disease Models,” Aging Cell 19, no. 1 (2020): e13054, https://doi.org/10.1111/acel.13054.

[213] S. L. Grillo, N. A. Duggett, A. Ennaceur, and P. L. Chazot, “Non-Invasive Infra-Red Therapy (1072 nm) Reduces β-Amyloid Protein Levels in the Brain of an Alzheimer's Disease Mouse Model, TASTPM,” Journal of Photochemistry and Photobiology B: Biology 123 (2013): 13-22, https://doi.org/10.1016/j.jphotobiol.2013.02.015.

[214] C. Chen, Y. Bao, L. Xing, et al., “Exosomes Derived From M2 Microglial Cells Modulated by 1070-nm Light Improve Cognition in an Alzheimer's Disease Mouse Model,” Advanced Science 10, no. 32 (2023): e2304025, https://doi.org/10.1002/advs.202304025.

[215] M. Wang, C. Yan, X. Li, et al., “Non-Invasive Modulation of Meningeal Lymphatics Ameliorates Ageing and Alzheimer's Disease-Associated Pathology and Cognition in Mice,” Nature Communications 15 (2024): 1453, https://doi.org/10.1038/s41467-024-45656-7.

RIGHTS & PERMISSIONS

2025 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.