Mitochondria-Targeted AIE Materials for Oxidative Stress-Mediated Cancer Therapy and Beyond

Na Hao , Bohong Chen , Xinxiang Wei , Yixuan Bao , Ru Zhang , Pu Chen , Jia Liu , Heqi Gao , Rongfu Tu , Chao Chen

Aggregate ›› 2025, Vol. 6 ›› Issue (12) : e70196

PDF
Aggregate ›› 2025, Vol. 6 ›› Issue (12) :e70196 DOI: 10.1002/agt2.70196
REVIEW
Mitochondria-Targeted AIE Materials for Oxidative Stress-Mediated Cancer Therapy and Beyond
Author information +
History +
PDF

Abstract

Mitochondria-targeted aggregation-induced emission (AIE) materials have emerged as promising candidates for precision medicine by enabling the controllable induction of oxidative stress within mitochondria. Yet, a comprehensive overview of the antitumor and other biological effects resulting from such oxidative stress remains lacking. This review summarizes the roles of both excessive and moderate oxidative stress triggered by mitochondria-targeted AIE materials across diverse applications, including: (1) direct induction of various forms of cancer cell death and degradation of cancer-associated proteins; (2) synergistic enhancement of chemo-, radio-, immune-, and other therapies; and (3) treatments beyond cancer. In addition, the challenges and key issues limiting their broader application are discussed. This review highlights the therapeutic potential of controllably induced oxidative stress by mitochondria-targeted AIE materials, aiming to accelerate their development for precise disease intervention and biological regulation.

Keywords

aggregation-induced emission / biological regulation / cancer therapy / mitochondrial / oxidative stress

Cite this article

Download citation ▾
Na Hao, Bohong Chen, Xinxiang Wei, Yixuan Bao, Ru Zhang, Pu Chen, Jia Liu, Heqi Gao, Rongfu Tu, Chao Chen. Mitochondria-Targeted AIE Materials for Oxidative Stress-Mediated Cancer Therapy and Beyond. Aggregate, 2025, 6(12): e70196 DOI:10.1002/agt2.70196

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

D. J. Betteridge, “What is Oxidative Stress?” Metabolism 49 (2000): 3–8.

[2]

N. R. Madamanchi, A. Vendrov, and M. S. Runge, “Oxidative Stress and Vascular Disease,” Arteriosclerosis, Thrombosis, and Vascular Biology 25 (2005): 29–38.

[3]

Z. Ďuračková, “Some Current Insights Into Oxidative Stress,” Physiological Research 59 (2009): 459–469.

[4]

H. Sies, C. Berndt, and D. P. Jones, “Oxidative Stress,” Annual Review of Biochemistry 86 (2017): 715–748.

[5]

Y. J. Suzuki, H. J. Forman, and A. Sevanian, “Oxidants as Stimulators of Signal Transduction,” Free Radical Biology and Medicine 22 (1997): 269–285.

[6]

W. Dröge, “Free Radicals in the Physiological Control of Cell Function,” Physiological Reviews 82 (2002): 47–95.

[7]

S. Xu and R. M. Touyz, “Reactive Oxygen Species and Vascular Remodelling in Hypertension: Still Alive,” Canadian Journal of Cardiology 22 (2006): 947–951.

[8]

V. Larosa and C. Remacle, “Insights Into the Respiratory Chain and Oxidative Stress,” Bioscience Reports 38 (2018): BSR20171492.

[9]

E. M. Digby, R. Rana, M. Nitz, and A. A. Beharry, “DNA Directed Damage Using a Brominated DAPI Derivative,” Chemical Communications 55 (2019): 9971–9974.

[10]

M. Wang, J. Song, F. Zhou, et al., “NIR-Triggered Phototherapy and Immunotherapy via an Antigen-Capturing Nanoplatform for Metastatic Cancer Treatment,” Advanced Science 6 (2019): 1802157.

[11]

A. S. Klymchenko, “Solvatochromic and Fluorogenic Dyes as Environment-Sensitive Probes: Design and Biological Applications,” Accounts of Chemical Research 50 (2017): 366–375.

[12]

J. Mei, N. L. Leung, R. T. Kwok, J. W. Lam, and B. Z. Tang, “Aggregation-Induced Emission: Together We Shine, United We Soar!,” Chemical Reviews 115 (2015): 11718–11940.

[13]

Kenry and B. Liu, “Bioorthogonal Reactions and AIEgen-Based Metabolically Engineered Theranostic Systems,” Chem 9 (2023): 2078–2094.

[14]

X. Tian, J. Cheng, L. Yang, Z. Li, and M. Yu, “A NIR Dual-Channel Fluorescent Probe for Fluctuations of Intracellular Polarity and H2O2 and Its Applications for the Visualization of Inflammation and Ferroptosis,” Chemical & Biomedical Imaging 2 (2024): 518–525.

[15]

H. Fang, M. Wang, P. Wei, et al., “Molecular Probes for Super-Resolution Imaging of Drug Dynamics,” Advanced Drug Delivery Reviews 210 (2024): 115330.

[16]

X.-Z. Yang, H. Fang, S. Li, et al., “Aggregation-Based Dual-Target Probe for Dual-Colour Super-Resolution Monitoring Mitophagy and Evaluating Drugs Regulating Mitochondria,” Aggregate 6 (2025): e641.

[17]

S. Wang, K. Zhou, X. Lyu, et al., “The Bioimaging Story of AIEgens,” Chemical & Biomedical Imaging 1 (2023): 509–521.

[18]

W. Wu, M. Ziemann, K. Huynh, et al., “Activation of Hippo Signaling Pathway Mediates Mitochondria Dysfunction and Dilated Cardiomyopathy in Mice,” Theranostics 11 (2021): 8993–9008.

[19]

D. J. Rowlands, “Mitochondria Dysfunction: A Novel Therapeutic Target in Pathological Lung Remodeling or Bystander?” Pharmacology & Therapeutics 166 (2016): 96–105.

[20]

O. Krestinina, Y. Baburina, R. Krestinin, I. Odinokova, I. Fadeeva, and L. Sotnikova, “Astaxanthin Prevents Mitochondrial Impairment Induced by Isoproterenol in Isolated Rat Heart Mitochondria,” Antioxidants (Basel) 9 (2020): 262.

[21]

P. J. Burke, “Mitochondria, Bioenergetics and Apoptosis in Cancer,” Trends in Cancer 3 (2017): 857–870.

[22]

H. Zhang, Z. Zhang, S. Wang, T. Qiu, T. Xu, and Y. Shu, “Apoptotic Induction of Mitochondria-Anchored Aggregation-Induced Emission Luminogens Through the Intrinsic Mitochondrial Pathway,” ACS Omega 7 (2022): 47912–47922.

[23]

Y. Tu, Y. Zhou, D. Zhang, et al., “Light-Induced Reactive Oxygen Species (ROS) Generator for Tumor Therapy Through an ROS Burst in Mitochondria and AKT-Inactivation-Induced Apoptosis,” ACS Applied Bio Materials 4 (2021): 5222–5230.

[24]

L. Wei, X. He, D. Zhao, M. Kandawa-Shultz, G. Shao, and Y. Wang, “Biotin-Conjugated Ru(II) Complexes With AIE Characteristics as Mitochondria-Targeted Photosensitizers for Enhancing Photodynamic Therapy by Disrupting Cellular Redox Balance,” European Journal of Medicinal Chemistry 264 (2024): 115985.

[25]

Sauraj, J. H. Kang, O. Lee, and Y. T. Ko, “Novel Aggregation-Induced Emission-Photosensitizers With Built-in Capability of Mitochondria Targeting and Glutathione Depletion for Efficient Photodynamic Therapy,” Nanoscale 15 (2023): 4882–4892.

[26]

J. Liu, X. Liu, M. Wu, G. Qi, and B. Liu, “Engineering Living Mitochondria With AIE Photosensitizer for Synergistic Cancer Cell Ablation,” Nano Letters 20 (2020): 7438–7445.

[27]

X. Liu, Y. Sun, Y. Gao, et al., “Anticancer Behavior of Cyclometallated Iridium(III)-Tributyltin(IV) Carboxylate Schiff Base Complexes With Aggregation-Induced Emission,” Journal of Inorganic Biochemistry 262 (2025): 112767.

[28]

H. T. Feng, Y. Li, X. Duan, et al., “Substitution Activated Precise Phototheranostics Through Supramolecular Assembly of AIEgen and Calixarene,” Journal of the American Chemical Society 142 (2020): 15966–15974.

[29]

Y. Wang, S. Xu, L. Shi, C. Teh, G. Qi, and B. Liu, “Cancer-Cell-Activated In Situ Synthesis of Mitochondria-Targeting AIE Photosensitizer for Precise Photodynamic Therapy,” Angewandte Chemie International Edition 60 (2021): 14945–14953.

[30]

D.-P. Wang, J. Zheng, F.-Y. Jiang, et al., “Facile and Green Fabrication of Tumor- and Mitochondria-Targeted AIEgen-Protein Nanoparticles for Imaging-Guided Photodynamic Cancer Therapy,” Acta Biomaterialia 168 (2023): 551–564.

[31]

T. Huang, H. Ji, S. Yan, et al., “A Hypochlorite-Activated Strategy for Realizing Fluorescence Turn-On, Type I and Type II ROS-Combined Photodynamic Tumor Ablation,” Biomaterials 297 (2023): 122108.

[32]

J.-W. Chen and C.-C. Chang, “A Dual Anticancer Efficacy Molecule: A Selective Dark Cytotoxicity Photosensitizer,” ACS Applied Materials & Interfaces 8 (2016): 29883–29892.

[33]

X. Yang, L. Cheng, Y. Zhao, et al., “Aggregation-Induced Emission-Active Iridium(III)-Based Mitochondria-Targeting Nanoparticle for two-Photon Imaging-Guided Photodynamic Therapy,” Journal of Colloid and Interface Science 659 (2024): 320–329.

[34]

W. Zhuang, L. Yang, B. Ma, et al., “Multifunctional Two-Photon AIE Luminogens for Highly Mitochondria-Specific Bioimaging and Efficient Photodynamic Therapy,” ACS Applied Materials & Interfaces 11 (2019): 20715–20724.

[35]

Y. Xiao, Y. Yuan, M. Liang, et al., “Efficient Type I and Type II ROS Generated Aggregation-Induced Emission Photosensitizer for Mitochondria Targeted Photodynamic Therapy,” Dyes and Pigments 220 (2023): 111765.

[36]

Z. Ma, Q. Wang, Z. Cai, Z. Chen, N. Li, and N. Zhao, “Benzothiazolium-Based NIR AIE Photosensitizers With Type I and II ROS Generation for Efficient Mitochondria-Targeted Photodynamic Therapy,” Luminescence 39 (2024): e4735.

[37]

T. Zhou, J. Zhu, D. Shang, et al., “Mitochondria-Anchoring and AIE-Active Photosensitizer for Self-Monitored Cholangiocarcinoma Therapy,” Materials Chemistry Frontiers 4 (2020): 3201–3208.

[38]

I. Dikic and Z. Elazar, “Mechanism and Medical Implications of Mammalian Autophagy,” Nature Reviews Molecular Cell Biology 19 (2018): 349–364.

[39]

N. Mizushima, T. Yoshimori, and B. Levine, “Methods in Mammalian Autophagy Research,” Cell 140 (2010): 313–326.

[40]

Z. Yang and D. J. Klionsky, “Eaten Alive: A History of Macroautophagy,” Nature Cell Biology 12 (2010): 814–822.

[41]

N. Mizushima and B. Levine, “Autophagy in Human Diseases,” New England Journal of Medicine 383 (2020): 1564–1576.

[42]

N. Mizushima, B. Levine, A. M. Cuervo, and D. J. Klionsky, “Autophagy Fights Disease Through Cellular Self-Digestion,” Nature 451 (2008): 1069–1075.

[43]

Y. Su, H. Lin, Y. Tu, et al., “Fighting Metallodrug Resistance Through Alteration of Drug Metabolism and Blockage of Autophagic Flux by Mitochondria-Targeting AIEgens,” Chemical Science 13 (2022): 1428–1439.

[44]

K. Peynshaert, B. B. Manshian, F. Joris, et al., “Exploiting Intrinsic Nanoparticle Toxicity: The Pros and Cons of Nanoparticle-Induced Autophagy in Biomedical Research,” Chemical Reviews 114 (2014): 7581–7609.

[45]

Y. Li, J. Zhuang, Y. Lu, et al., “High-Performance Near-Infrared Aggregation-Induced Emission Luminogen With Mitophagy Regulating Capability for Multimodal Cancer Theranostics,” ACS Nano 15 (2021): 20453–20465.

[46]

G.-D. Zhang, M.-M. Wang, Y. Su, et al., “Mitochondria-Targeted Ruthenium Complexes Can be Generated in Vitro and in Living Cells to Target Triple-Negative Breast Cancer Cells by Autophagy Inhibition,” Journal of Inorganic Biochemistry 256 (2024): 112574.

[47]

S. Pickles, P. Vigié, and R. J. Youle, “Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance,” Current Biology 28 (2018): R170–R185.

[48]

H. Katayama, H. Hama, K. Nagasawa, et al., “Visualizing and Modulating Mitophagy for Therapeutic Studies of Neurodegeneration,” Cell 181 (2020): 1176–1187.

[49]

P. M. Quirós, T. Langer, and C. López-Otín, “New Roles for Mitochondrial Proteases in Health, Ageing and Disease,” Nature Reviews Molecular Cell Biology 16 (2015): 345–359.

[50]

Y.-X. Zhu, H.-R. Jia, G. Gao, et al., “Mitochondria-Acting Nanomicelles for Destruction of Cancer Cells via Excessive Mitophagy/Autophagy-Driven Lethal Energy Depletion and Phototherapy,” Biomaterials 232 (2020): 119668.

[51]

Y. Peng, R. Mo, M. Yang, et al., “Mitochondria-Targeting AIEgens as Pyroptosis Inducers for Boosting Type-I Photodynamic Therapy of Tongue Squamous Cell Carcinoma,” ACS Nano 18 (2024): 26140–26152.

[52]

F. J. Bock and S. W. G. Tait, “Mitochondria as Multifaceted Regulators of Cell Death,” Nature Reviews Molecular Cell Biology 21 (2020): 85–100.

[53]

P. Yu, X. Zhang, N. Liu, L. Tang, C. Peng, and X. Chen, “Pyroptosis: Mechanisms and Diseases,” Signal Transduction and Targeted Therapy 6 (2021): 128.

[54]

K. Yu, B. Ye, H. Yang, et al., “A Mitochondria-Targeted NIR-II AIEgen Induced Pyroptosis for Enhanced Tumor Immunotherapy,” Advanced Healthcare Materials 12 (2023): e2301693.

[55]

K. Dong, Y. Xu, Y. Tang, and Q. Li, “Photoactivated Self-Assembled Nanomicelles Integrating Mitophagy Inhibition to Enhance Pyroptosis for Cancer Immunotherapy,” Advanced Functional Materials 35 (2025): 2504384.

[56]

J. Cao, Y. Qu, S. Zhu, et al., “Safe Transportation and Targeted Destruction: Albumin Encapsulated Aggregation-Induced Emission Photosensitizer Nanoaggregate for Tumor Photodynamic Therapy Through Mitochondria Damage-Triggered Pyroptosis,” Aggregate 5 (2024): e637.

[57]

Y. Fuchs and H. Steller, “Programmed Cell Death in Animal Development and Disease,” Cell 147 (2011): 742–758.

[58]

S. Bedoui, M. J. Herold, and A. Strasser, “Emerging Connectivity of Programmed Cell Death Pathways and its Physiological Implications,” Nature Reviews Molecular Cell Biology 21 (2020): 678–695.

[59]

J. Zhuang, Z. Ma, N. Li, et al., “Molecular Engineering of Plasma Membrane and Mitochondria Dual-Targeted NIR-II AIE Photosensitizer Evoking Synergetic Pyroptosis and Apoptosis,” Advanced Materials 36 (2024): 2309488.

[60]

H. Su, W. Shang, G. Li, et al., “Near-Infrared II AIE Luminogens With Mitochondria-Targeting Characteristics for Combinational Phototherapies of Breast Tumors Through Synergistic Cell Apoptosis and Pyroptosis,” Advanced Functional Materials 35 (2025): 2414976.

[61]

B. Wang, H. Zhou, L. Chen, et al., “A Mitochondria-Targeted Photosensitizer for Combined Pyroptosis and Apoptosis With NIR-II Imaging/Photoacoustic Imaging-Guided Phototherapy,” Angewandte Chemie International Edition 63 (2024): e202408874.

[62]

S. Liu, Y. Pei, Y. Sun, et al., “‘Three Birds With One Stone’ Nanoplatform: Efficient Near-Infrared-Triggered Type‑I AIE Photosensitizer for Mitochondria-Targeted Photodynamic Therapy Against Hypoxic Tumors,” Aggregate 5 (2024): e547.

[63]

J. Zhuang, B. Wang, H. Chen, et al., “Efficient NIR-II Type-I AIE Photosensitizer for Mitochondria-Targeted Photodynamic Therapy Through Synergistic Apoptosis–Ferroptosis,” ACS Nano 17 (2023): 9110–9125.

[64]

S. Wang, Y. Qiu, L. Yu, et al., “Molecular Engineering Strategies for Fabricating Type-I Mitochondria-Targeted Aggregation-Induced Emission Photosensitizers for Apoptosis-Ferroptosis Synergistically Boosting Photodynamic Therapy,” Journal of Colloid & Interface Science 694 (2025): 137680.

[65]

J. Wang, M. Cao, L. Han, et al., “Blood–Brain Barrier-Penetrative Fluorescent Anticancer Agents Triggering Paraptosis and Ferroptosis for Glioblastoma Therapy,” Journal of the American Chemical Society 146 (2024): 28783–28794.

[66]

P. Wang, H. Fang, M. Wang, et al., “A Mitochondria Targeting Ir(III) Complex Triggers Ferroptosis and Autophagy for Cancer Therapy: A Case of Aggregation Enhanced PDT Strategy for Metal Complexes,” Chinese Chemical Letters 36 (2025): 110099.

[67]

L. Zhang, A. Song, Q.-C. Yang, et al., “Integration of AIEgens Into Covalent Organic Frameworks for Pyroptosis and Ferroptosis Primed Cancer Immunotherapy,” Nature Communications 14 (2023): 5355.

[68]

Y. Wang, C. Chai, W. Lin, et al., “Oxidative Stress-Mediated PANoptosis and Ferroptosis: Exploration of Multimodal Cell Death Triggered by an AIE-Active Nano-Photosensitizer via Photodynamic Therapy,” Theranostics 15 (2025): 6665–6685.

[69]

Y. Wang, Y. Xu, Y. Qu, et al., “Ferroptosis: A Novel Cell Death Modality As a Synergistic Therapeutic Strategy With Photodynamic Therapy,” Photodiagnosis Photodynamic Therapy 51 (2025): 104463.

[70]

D. V. Krysko, A. D. Garg, A. Kaczmarek, O. Krysko, P. Agostinis, and P. Vandenabeele, “Immunogenic Cell Death and DAMPs in Cancer Therapy,” Nature Reviews Cancer 12 (2012): 860–875.

[71]

D. R. Green, T. Ferguson, L. Zitvogel, and G. Kroemer, “Immunogenic and Tolerogenic Cell Death,” Nature Reviews Immunology 9 (2009): 353–363.

[72]

Y. Fan, R. Kuai, Y. Xu, L. J. Ochyl, D. J. Irvine, and J. J. Moon, “Immunogenic Cell Death Amplified by Co-Localized Adjuvant Delivery for Cancer Immunotherapy,” Nano Letters 17 (2017): 7387–7393.

[73]

L. Galluzzi, A. Buqué, O. Kepp, L. Zitvogel, and G. Kroemer, “Immunogenic Cell Death in Cancer and Infectious Disease,” Nature Reviews Immunology 17 (2017): 97–111.

[74]

G. Kroemer, L. Galluzzi, O. Kepp, and L. Zitvogel, “Immunogenic Cell Death in Cancer Therapy,” Annual Review of Immunology 31 (2013): 51–72.

[75]

C. Chen, X. Ni, S. Jia, et al., “Massively Evoking Immunogenic Cell Death by Focused Mitochondrial Oxidative Stress Using an AIE Luminogen With a Twisted Molecular Structure,” Advanced Materials 31 (2019): 1904914.

[76]

P. Liu, F. Ren, S. Son, et al., “Mitochondrial Targeted AIEgen Phototheranostics for Bypassing Immune Barrier via Encumbering Mitochondria Functions,” Biomaterials 283 (2022): 121409.

[77]

L. Yang, J. Huang, Y. Liao, et al., “Strategically Designed Mitochondria-Targeting AIEgens for Effective Eradication of Primary and Metastatic Tumors via Synergistic Phototherapy and Induced Immunogenic Cell Death,” Advanced Healthcare Materials 14 (2025): 2500513.

[78]

K.-H. Li, H.-Y. Zhao, D.-D. Wang, et al., “Mitochondria-Targeted Nano-AIEgens as a Powerful Inducer for Evoking Immunogenic Cell Death,” Chinese Chemical Letters 35 (2024): 108882.

[79]

Q. Wu, L. Jiang, S. C. Li, Q. J. He, B. Yang, and J. Cao, “Small Molecule Inhibitors Targeting the PD-1/PD-L1 Signaling Pathway,” Acta Pharmacologica Sinica 42 (2021): 1–9.

[80]

S. H. Lecker, A. L. Goldberg, and W. E. Mitch, “Protein Degradation by the Ubiquitin–Proteasome Pathway in Normal and Disease States,” Journal of the American Society of Nephrology 17 (2006): 1807–1819.

[81]

M. C. Gomes-Marcondes and M. J. Tisdale, “Induction of Protein Catabolism and the Ubiquitin-Proteasome Pathway by Mild Oxidative Stress,” Cancer Letters 180 (2002): 69–74.

[82]

J. Liu, R. Zhang, Y. Bao, et al., “Highly Efficient and Universal Degradation of PD-L1 via Mitochondrial Oxidative Stress Evoked by Cationic AIE-Active Photosensitizers for Cancer Immunotherapy,” Advanced Functional Materials 35 (2025): 2414495.

[83]

M. Wang, Z. Yang, Y. Song, et al., “Proteasomal and Autophagy-Mediated Degradation of mutp53 Proteins Through Mitochondria-Targeting Aggregation-Induced-Emission Materials,” Acta Biomaterialia 150 (2022): 402–412.

[84]

A. Kythreotou, A. Siddique, F. A. Mauri, M. Bower, and D. J. Pinato, “PD-L1,” Journal of Clinical Pathology 71 (2018): 189–194.

[85]

L. Chen and X. Han, “Anti–PD-1/PD-L1 Therapy of Human Cancer: Past, Present, and Future,” Journal of Clinical Investigation 125 (2015): 3384–3391.

[86]

Y. Xia, X. Li, N. Bie, et al., “A Method for Predicting Drugs That Can Boost the Efficacy of Immune Checkpoint Blockade,” Nature Immunology 25 (2024): 659–670.

[87]

X. He, Y. Luo, Y. Li, et al., “D-Type Neuropeptide Decorated AIEgen/RENP Hybrid Nanoprobes With Light-Driven ROS Generation Ability for NIR-II Fluorescence Imaging-Guided Through-Skull Photodynamic Therapy of Gliomas,” Aggregate 5 (2024): e396.

[88]

T. Soussi and C. Béroud, “Assessing TP53 Status in Human Tumours to Evaluate Clinical Outcome,” Nature Reviews Cancer 1 (2001): 233–239.

[89]

Y. Haupt, R. Maya, A. Kazaz, and M. Oren, “Mdm2 Promotes the Rapid Degradation of p53,” Nature 387 (1997): 296–299.

[90]

C. Kandoth, M. D. McLellan, F. Vandin, et al., “Mutational Landscape and Significance Across 12 Major Cancer Types,” Nature 502 (2013): 333–339.

[91]

M. P. Kim and G. Lozano, “Mutant p53 Partners in Crime,” Cell Death and Differentiation 25 (2018): 161–168.

[92]

X. Wang, X. Zhang, G. Zheng, et al., “Design and Synthesis of Pentacyclic Triterpene Conjugates and Their Use in Medicinal Research,” European Journal of Medicinal Chemistry 264 (2024): 115975.

[93]

J. Wang, W. Zhang, T. Wu, et al., “Photodynamic Antitumor Activity of Aggregation-Induced Emission Luminogens as Chemosensitizers for Paclitaxel by Concurrent Induction of Apoptosis and Autophagic Cell Death,” Materials Chemistry Frontiers 5 (2021): 3448–3457.

[94]

Y. Su, Y. Tu, H. Lin, et al., “Mitochondria-Targeted Pt(IV) Prodrugs Conjugated With an Aggregation-Induced Emission Luminogen Against Breast Cancer Cells by Dual Modulation of Apoptosis and Autophagy Inhibition,” Journal of Inorganic Biochemistry 226 (2022): 111653.

[95]

B. Guo, M. Wu, Q. Shi, et al., “All-in-One Molecular Aggregation-Induced Emission Theranostics: Fluorescence Image Guided and Mitochondria Targeted Chemo- and Photodynamic Cancer Cell Ablation,” Chemistry of Materials 32 (2020): 4681–4691.

[96]

G. Feng, J. Liu, C.-J. Zhang, and B. Liu, “Artemisinin and AIEgen Conjugate for Mitochondria-Targeted and Image-Guided Chemo- and Photodynamic Cancer Cell Ablation,” ACS Applied Materials & Interfaces 10 (2018): 11546–11553.

[97]

J. Wang, H. Wu, Q. Zhao, et al., “Aggregation-Induced Emission Photosensitizer Synergizes Photodynamic Therapy and the Inhibition of the NF-κB Signaling Pathway to Overcome Hypoxia in Breast Cancer,” ACS Applied Materials & Interfaces 14 (2022): 29613–29625.

[98]

C. Y. Y. Yu, H. Xu, S. Ji, et al., “Mitochondrion-Anchoring Photosensitizer with Aggregation-Induced Emission Characteristics Synergistically Boosts the Radiosensitivity of Cancer Cells to Ionizing Radiation,” Advanced Materials 29 (2017): 1606167.

[99]

R. Wang, S. Deng, Z. Liu, et al., “A Near-Infrared Aggregation-Induced Emission Photosensitizer with Mitochondria Specificity Enhances Radiotherapy for Cancer Stem Cells Ablation,” Journal of Materials Chemistry B 13 (2025): 8725–8731.

[100]

X. Li, Y. Sun, Y. Wang, et al., “Amplifying Radiotherapy by Evoking Mitochondrial Oxidative Stress Using a High-Performance Aggregation-Induced Emission Sonosensitizer,” Current Medicinal Chemistry 32 (2025): 380–395.

[101]

Z. Sun, H. Wen, Z. Zhang, et al., “Acceptor Engineering-Facilitated Versatile AIEgen for Mitochondria-Targeted Multimodal Imaging-Guided Cancer Photoimmunotherapy,” Biomaterials 301 (2023): 122276.

[102]

H. Cao, H. Gao, L. Wang, et al., “Biosynthetic Dendritic Cell-Exocytosed Aggregation-Induced Emission Nanoparticles for Synergistic Photodynamic Immunotherapy,” ACS Nano 16 (2022): 13992–14006.

[103]

Q. Feng, J. Xu, C. Zhuang, J. Xiong, H. Wang, and K. Xiao, “Mitochondria-Targeting and Multiresponsive Nanoplatform Based on AIEgens for Synergistic Chemo-Photodynamic Therapy and Enhanced Immunotherapy,” Biomacromolecules 24 (2023): 977–990.

[104]

T. Zhang, Z. Liu, W. Tang, et al., “Mitochondria-Targeting Type I AIE Photosensitizer Combined with H2S Therapy: Uninterrupted Hydroxyl Radical Generation for Enhancing Tumor Therapy,” Nano Today 46 (2022): 101620.

[105]

Y. Yu, L. Zhang, H. Jia, et al., “Dual-Mode Reactive Oxygen Species-Stimulated Carbon Monoxide Release for Synergistic Photodynamic and Gas Tumor Therapy,” ACS Nano 18 (2024): 31286–31299.

[106]

Y. Chen, W. Ai, X. Guo, et al., “Mitochondria-Targeted Polydopamine Nanocomposite with AIE Photosensitizer for Image-Guided Photodynamic and Photothermal Tumor Ablation,” Small 15 (2019): e1902352.

[107]

S. Wang, C. Chen, J. Wu, et al., “A Mitochondria-Targeted AIE Photosensitizer for Enhancing Specificity and Efficacy of Ferroptosis Inducer,” Science China Chemistry 65 (2022): 870–876.

[108]

M. Kowalik, J. Masternak, and B. Barszcz, “Recent Research Trends on Bismuth Compounds in Cancer Chemo and Radiotherapy,” Current Medicinal Chemistry 26 (2019): 729–759.

[109]

M.-C. Vozenin, J. Bourhis, and M. Durante, “Towards Clinical Translation of FLASH Radiotherapy,” Nature Reviews Clinical oncology 19 (2022): 791–803.

[110]

D. De Ruysscher, G. Niedermann, N. G. Burnet, S. Siva, A. W. M. Lee, and F. Hegi-Johnson, “Radiotherapy Toxicity,” Nature Reviews Disease Primers 5 (2019): 13.

[111]

R. A. Chandra, F. K. Keane, F. E. M. Voncken, and C. R. Thomas, “Contemporary Radiotherapy: Present and Future,” Lancet 398 (2021): 171–184.

[112]

Y. Duo, Z. Chen, K. Li, et al., “Targeted Delivery of Novel Au(I)-Based AIEgen via Inactivated Cancer Cells for Trimodal Chemo-Radio-Immunotherapy and Vaccination Against Advanced Tumor,” Nano Today 51 (2023): 101920.

[113]

P. Robinson, R. Coveñas, and M. Muñoz, “Combination Therapy of Chemotherapy or Radiotherapy and the Neurokinin-1 Receptor Antagonist Aprepitant: A New Antitumor Strategy?,” Current Medicinal Chemistry 30 (2023): 1798–1812.

[114]

J. Liu, F. Hu, M. Wu, et al., “Bioorthogonal Coordination Polymer Nanoparticles With Aggregation-Induced Emission for Deep Tumor-Penetrating Radio- and Radiodynamic Therapy,” Advanced Materials 33 (2021): e2007888.

[115]

C. Yang, X. Ni, D. Mao, et al., “Seeing the Fate and Mechanism of Stem Cells in Treatment of Ionizing Radiation-Induced Injury Using Highly Near-Infrared Emissive AIE Dots,” Biomaterials 188 (2019): 107–117.

[116]

Y. Duo, Z. Chen, Z. Li, et al., “Combination of Bacterial-Targeted Delivery of Gold-Based AIEgen Radiosensitizer for Fluorescence-Image-Guided Enhanced Radio-Immunotherapy Against Advanced Cancer,” Bioactive Materials 30 (2023): 200–213.

[117]

K. J. Hiam-Galvez, B. M. Allen, and M. H. Spitzer, “Systemic Immunity in Cancer,” Nature Reviews Cancer 21 (2021): 345–359.

[118]

S. K. Singh and R. Singh, “Nanotherapy: Targeting the Tumour Microenvironment,” Nature Reviews Cancer 22 (2022): 258.

[119]

W. J. Ho, E. M. Jaffee, and L. Zheng, “The Tumour Microenvironment in Pancreatic Cancer—Clinical Challenges and Opportunities,” Nature Reviews Clinical Oncology 17 (2020): 527–540.

[120]

A. Kalbasi and A. Ribas, “Tumour-Intrinsic Resistance to Immune Checkpoint Blockade,” Nature Reviews Immunology 20 (2020): 25–39.

[121]

J. Sprooten, J. Ceusters, A. Coosemans, et al., “Trial Watch: Dendritic Cell Vaccination for Cancer Immunotherapy,” Oncoimmunology 8 (2019): 1638212.

[122]

J. Li, H. Zeng, L. Li, Q. Yang, L. He, and M. Dong, “Advanced Generation Therapeutics: Biomimetic Nanodelivery System for Tumor Immunotherapy,” ACS Nano 17 (2023): 24593–24618.

[123]

W.-D. Wang, Y.-Y. Guo, Z.-L. Yang, G.-L. Su, and Z.-J. Sun, “Sniping Cancer Stem Cells With Nanomaterials,” ACS Nano 17 (2023): 23262–23298.

[124]

L. Xu, Q. Zhang, X. Wang, and W. Lin, “Biomimetic Theranostic Nano-Agents Based on NIR Organic Small Molecules,” Coordination Chemistry Reviews 543 (2025): 216910.

[125]

Y. Li, J. Yang, S. Shen, and J. Ding, “Exosomes-Incorporated Biomaterials Boost Cancer Immunotherapy,” Nano Today 64 (2025): 102805.

[126]

Q. Perrier, V. Lisi, K. Fisherwellman, et al., “Therapeutic Transplantation of Mitochondria and Extracellular Vesicles: Mechanistic Insights Into Mitochondria Bioenergetics, Redox Signaling, and Organelle Dynamics in Preclinical Models,” Free Radical Biology and Medicine 238 (2025): 473–495.

[127]

X. Xu, L. Chen, L. Yang, et al., “Top-Down Bioinspired Nanotheranostics With AIE Luminogens,” Coordination Chemistry Reviews 537 (2025): 216681.

[128]

D. Wang, X. Liu, X. Zhang, et al., “A Metabolism-Oriented Strategy to Directly Generate Photosensitizer-Engineered Extracellular Vesicles From Cancer Cells,” Advanced Materials 37 (2025): e2505726.

[129]

P. Ji, K. Yang, Q. Xu, et al., “Mechanisms and Application of Gas-Based Anticancer Therapies,” Pharmaceuticals 16 (2023): 1394.

[130]

L. Yu, P. Hu, and Y. Chen, “Gas-Generating Nanoplatforms: Material Chemistry, Multifunctionality, and Gas Therapy,” Advanced Materials 30 (2018): 1801964.

[131]

J. Meng, Z. Jin, P. Zhao, B. Zhao, M. Fan, and Q. He, “A Multistage Assembly/Disassembly Strategy for Tumor-Targeted CO Delivery,” Science Advances 6 (2020): eaba1362.

[132]

Q. He, D. O. Kiesewetter, Y. Qu, et al., “NIR-Responsive On-Demand Release of CO From Metal Carbonyl-Caged Graphene Oxide Nanomedicine,” Advanced Materials 27 (2015): 6741–6746.

[133]

M. Chaves-Ferreira, I. S. Albuquerque, D. Matak-Vinkovic, et al., “Spontaneous CO Release From Ru II (CO) 2 –Protein Complexes in Aqueous Solution, Cells, and Mice,” Angewandte Chemie International Edition 54 (2015): 1172–1175.

[134]

C. Chen, R. Zhang, J. Zhang, et al., “Taming Reactive Oxygen Species: Mitochondria-Targeting Aggregation-Induced Emission Luminogen for Neuron Protection via Photosensitization-Triggered Autophagy,” CCS Chemistry 4 (2022): 2249–2257.

[135]

C. Zhou, C. Peng, C. Shi, et al., “Mitochondria-Specific Aggregation-Induced Emission Luminogens for Selective Photodynamic Killing of Fungi and Efficacious Treatment of Keratitis,” ACS Nano 15 (2021): 12129–12139.

[136]

S. Wu, R. Song, T. Liu, and C. Li, “Antifungal Therapy: Novel Drug Delivery Strategies Driven by new Targets,” Advanced Drug Delivery Reviews 199 (2023): 114967.

[137]

N. H. Georgopapadakou, “Antifungals: Mechanism of Action and Resistance, Established and Novel Drugs,” Current Opinion in Microbiology 1 (1998): 547–557.

[138]

L. Chatre and M. Ricchetti, “Are Mitochondria the Achilles' Heel of the Kingdom Fungi?,” Current Opinion in Microbiology 20 (2014): 49–54.

RIGHTS & PERMISSIONS

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

PDF

3

Accesses

0

Citation

Detail

Sections
Recommended

/