Biomedical applications of stimuli-responsive nanomaterials

Abstract

Nanomaterials have aroused great interests in drug delivery due to their nanoscale structure, facile modifiability, and multifunctional physicochemical properties. Currently, stimuli-responsive nanomaterials that can respond to endogenous or exogenous stimulus display strong potentials in biomedical applications. In comparison with conventional nanomaterials, stimuli-responsive nanomaterials can improve therapeutic efficiency and reduce the toxicity of drugs toward normal tissues through specific targeting and on-demand drug release at pathological sites. In this review, we summarize the responsive mechanism of a variety of stimulus, including pH, redox, and enzymes within pathological microenvironment, as well as exogenous stimulus such as thermal effect, magnetic field, light, and ultrasound. After that, biomedical applications (e.g., drug delivery, imaging, and theranostics) of stimuli-responsive nanomaterials in a diverse array of common diseases, including cardiovascular diseases, cancer, neurological disorders, inflammation, and bacterial infection, are presented and discussed. Finally, the remaining challenges and outlooks of future research directions for the biomedical applications of stimuli-responsive nanomaterials are also discussed. We hope that this review can provide valuable guidance for developing stimuli-responsive nanomaterials and accelerate their biomedical applications in diseases diagnosis and treatment.

Keywords

biomedical applications / drug delivery / imaging / pathological environment / stimuli-responsive nanomaterials / theranostics

References

[1] Abid N, Khan M, Shujait S, et al. Synthesis of nanomaterials using various top-down and bottom-up approaches, influencing factors, advantages, and disadvantages: a review. Adv Colloid Interface Sci. 2022; 300: 102597.

[2] Malik S, Muhammad K, Waheed Y. Nanotechnology: a revolution in modern industry. Molecules. 2023; 28(2): 661.

[3] Yao J, Feng J, Chen J. External-stimuli responsive systems for cancer theranostic. Asian J Pharm Sci. 2016; 11(5): 585-595.

[4] Pham SH, Choi Y, Choi J. Stimuli-responsive nanomaterials for application in antitumor therapy and drug delivery. Pharmaceutics. 2020; 12(7): 630.

[5] Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol. 2018; 16: 71.

[6] Bauri S, Tripathi S, Choudhury AM, Mandal SS, Raj H, Maiti P. Nanomaterials as theranostic agents for cancer therapy. ACS Appl Nano Mater. 2023; 6(23): 21462-21495.

[7] Rinaldi A, Caraffi R, Grazioli MV, et al. Applications of the ROS-responsive thioketal linker for the production of smart nanomedicines. Polymers. 2022; 14(4): 687.

[8] Ang MJY, Chan SY, Goh Y-Y, Luo Z, Lau JW, Liu X. Emerging strategies in developing multifunctional nanomaterials for cancer nanotheranostics. Adv Drug Del Rev. 2021; 178: 113907.

[9] Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nat Mater. 2013; 12(11): 991-1003.

[10] Yang Y, Wu H, Liu B, Liu Z. Tumor microenvironment-responsive dynamic inorganic nanoassemblies for cancer imaging and treatment. Adv Drug Del Rev. 2021; 179: 114004.

[11] Li S, Li W, Khashab NM. Stimuli responsive nanomaterials for controlled release applications. Nanotechnol Rev. 2012; 1(6): 493-513.

[12] Li L, Yang W, Xu D. Stimuli-responsive nanoscale drug delivery systems for cancer therapy. J Drug Target. 2019; 27(4): 423-433.

[13] Huang J, Zhang X, Fu K, Wei G, Su Z. Stimulus-responsive nanomaterials under physical regulation for biomedical applications. J Mater Chem B. 2021; 9(47): 9642-9657.

[14] Xiao W, Zhao L, Sun Y, Yang X, Fu Q. Stimuli-responsive nanoradiosensitizers for enhanced cancer radiotherapy. Small Methods. 2024; 8(1): e2301131.

[15] Tian M, Xin X, Wu R, Guan W, Zhou W. Advances in intelligent-responsive nanocarriers for cancer therapy. Pharmacol Res. 2022; 178: 106184.

[16] Lavrador P, Esteves MR, Gaspar VM, Mano JF. Stimuli-responsive nanocomposite hydrogels for biomedical applications. Adv Funct Mater. 2021; 31(8): 2005941.

[17] Wei D, Sun Y, Zhu H, Fu Q. Stimuli-responsive polymer-based nanosystems for cancer theranostics. ACS Nano. 2023; 17(23): 23223-23261.

[18] Mu R, Zhu D, Abdulmalik S, Wijekoon S, Wei G, Kumbar SG. Stimuli-responsive peptide assemblies: design, self-assembly, modulation, and biomedical applications. Bioact Mater. 2024; 35: 181-207.

[19] Zhang M, Tong W. Stimuli-responsive nanozymes for biomedical applications. Biomater Sci. 2023; 11(17): 5769-5780.

[20] Lee Y, Thompson DH. Stimuli-responsive liposomes for drug delivery. Wires Nanomed Nanobi. 2017; 9(5): e1450.

[21] Qiao Y, Wan J, Zhou L, et al. Stimuli-responsive nanotherapeutics for precision drug delivery and cancer therapy. Wires Nanomed Nanobi. 2019; 11(1): e1527.

[22] Du J, Lane LA, Nie S. Stimuli-responsive nanoparticles for targeting the tumor microenvironment. J Control Release. 2015; 219: 205-214.

[23] Cai W, Wang J, Chu C, Chen W, Wu C, Liu G. Metal organic framework-based stimuli-responsive systems for drug delivery. Adv Sci. 2019; 6(1): 1801526.

[24] Wang Y, Yan J, Wen N, et al. Metal-organic frameworks for stimuli-responsive drug delivery. Biomaterials. 2020; 230: 119619.

[25] Fu L, Sun C, Yan L. Galactose targeted pH-responsive copolymer conjugated with near infrared fluorescence probe for imaging of intelligent drug delivery. ACS Appl Mater Interfaces. 2015; 7(3): 2104-2115.

[26] Lu L, Wang K, Lin C, et al. Constructing nanocomplexes by multicomponent self-assembly for curing orthotopic glioblastoma with synergistic chemo-photothermal therapy. Biomaterials. 2021; 279: 121193.

[27] Fang F, Wang S, Song Y, et al. Continuous spatiotemporal therapy of a full-API nanodrug via multi-step tandem endogenous biosynthesis. Nat Commun. 2023; 14(1): 1660.

[28] Liu Y, Zou Y, Feng C, et al. Charge conversional biomimetic nanocomplexes as a multifunctional platform for boosting orthotopic glioblastoma RNAi therapy. Nano Lett. 2020; 20(3): 1637-1646.

[29] Sathiyaseelan A, Saravanakumar K, Mariadoss AVA, Wang M-H. pH-controlled nucleolin targeted release of dual drug from chitosan-gold based aptamer functionalized nano drug delivery system for improved glioblastoma treatment. Carbohydr Polym. 2021; 262: 117907.

[30] Dousti F, Soleimanbeigi M, Mirian M, et al. Boron phenyl alanine targeted ionic liquid decorated chitosan nanoparticles for mitoxantrone delivery to glioma cell line. Pharm Dev Technol. 2021; 26(8): 899-909.

[31] Ding H, Li B, Jiang Y, et al. pH-responsive UV crosslinkable chitosan hydrogel via “thiol-ene” click chemistry for active modulating opposite drug release behaviors. Carbohydr Polym. 2021; 251: 117101.

[32] Jiang Y, Wang X, Liu X, et al. Enhanced antiglioma efficacy of ultrahigh loading capacity paclitaxel prodrug conjugate self-assembled targeted nanoparticles. ACS Appl Mater Interfaces. 2017; 9(1): 211-217.

[33] Liu X, Li Y, Wang K, et al. GSH-responsive nanoprodrug to inhibit glycolysis and alleviate immunosuppression for cancer therapy. Nano Lett. 2021; 21(18): 7862-7869.

[34] Li Z, Hu J, Xu Q, et al. A redox-responsive drug delivery system based on RGD containing peptide-capped mesoporous silica nanoparticles. J Mater Chem B. 2015; 3(1): 39-44.

[35] Wen L, Peng Y, Wang K, et al. Regulation of pathological BBB restoration via nanostructured ROS-responsive glycolipid-like copolymer entrapping siVEGF for glioblastoma targeted therapeutics. Nano Res. 2022; 15(2): 1455-1465.

[36] Chu B, Qu Y, He X, et al. ROS-responsive camptothecin prodrug nanoparticles for on-demand drug release and combination of chemotherapy and photodynamic therapy. Adv Funct Mater. 2020; 30(52): 2005918.

[37] Ding B, Zheng P, Ma Pa, Lin J. Manganese oxide nanomaterials: synthesis, properties, and theranostic applications. Adv Mater. 2020; 32(10): 1905823.

[38] Liu X, Zhou Y, Xie W, Liu S, Zhao Q, Huang W. Construction of smart manganese dioxide-based all-in-one nanoplatform for cancer diagnosis and therapy. Small Methods. 2020; 4(12): 2000566.

[39] Lin L, Song J, Song L, et al. Simultaneous Fenton-like ion delivery and glutathione depletion by MnO2-based nanoagent to enhance chemodynamic therapy. Angew Chem Int Edit. 2018; 57(18): 4902-4906.

[40] Meng L, Cheng Y, Tong X, et al. Tumor oxygenation and hypoxia inducible factor-1 functional inhibition via a reactive oxygen species responsive nanoplatform for enhancing radiation therapy and abscopal effects. ACS Nano. 2018; 12(8): 8308-8322.

[41] Chen X, Zou J, Zhang K, et al. Photothermal/matrix metalloproteinase-2 dual-responsive gelatin nanoparticles for breast cancer treatment. Acta Pharm Sin B. 2021; 11(1): 271-282.

[42] Wu D, Zhou J, Zheng Y, et al. Pathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke. Nat Commun. 2023; 14(1): 7147.

[43] Zhu H, Cao X, Cai X, et al. Pifithrin-mu incorporated in gold nanoparticle amplifies pro-apoptotic unfolded protein response cascades to potentiate synergistic glioblastoma therapy. Biomaterials. 2020; 232: 119677.

[44] Shi D, Mi G, Shen Y, Webster TJ. Glioma-targeted dual functionalized thermosensitive Ferri-liposomes for drug delivery through an in vitro blood-brain barrier. Nanoscale. 2019; 11(32): 15057-15071.

[45] Senturk F, Cakmak S, Kocum IC, Gumusderelioglu M, Ozturk GG. GRGDS-conjugated and curcumin-loaded magnetic polymeric nanoparticles for the hyperthermia treatment of glioblastoma cells. Colloid Surface A. 2021; 622: 126648.

[46] Wang X, Wang L, Tan X, Zhang H, Sun G. Construction of doxorubicin-loading magnetic nanocarriers for assaying apoptosis of glioblastoma cells. J Colloid Interface Sci. 2014; 436: 267-275.

[47] Zhong Y, Wang C, Cheng R, et al. cRGD-directed, NIR-responsive and robust AuNR/PEG-PCL hybrid nanoparticles for targeted chemotherapy of glioblastoma in vivo. J Control Release. 2014; 195: 63-71.

[48] Kim C, Guo Y, Velalopolou A, et al. Closed-loop trans-skull ultrasound hyperthermia leads to improved drug delivery from thermosensitive drugs and promotes changes in vascular transport dynamics in brain tumors. Theranostics. 2021; 11(15): 7276-7293.

[49] Sabourian P, Ji J, Lotocki V, et al. Facile design of autogenous stimuli-responsive chitosan/hyaluronic acid nanoparticles for efficient small molecules to protein delivery. J Mater Chem B. 2020; 8(32): 7275-7287.

[50] Song P, Song N, Li L, Wu M, Lu Z, Zhao X. Angiopep-2-modified carboxymethyl chitosan-based pH/reduction dual-stimuli-responsive nanogels for enhanced targeting glioblastoma. Biomacromolecules. 2021; 22(7): 2921-2934.

[51] Cao Y, Jin L, Zhang S, et al. Blood-brain barrier permeable and multi-stimuli responsive nanoplatform for orthotopic glioma inhibition by synergistic enhanced chemo-/chemodynamic/photothermal/starvation therapy. Eur J Pharm Sci. 2023; 180: 106319.

[52] Naeem F, Khan S, Jalil A, et al. pH responsive cross-linked polymeric matrices based on natural polymers: effect of process variables on swelling characterization and drug delivery properties. Bioimpacts. 2017; 7(3): 177-192.

[53] Swietach P, Vaughan-Jones RD, Harris AL, Hulikova A. The chemistry, physiology and pathology of pH in cancer. Philos Trans R Soc B. 2014; 369(1638): 20130099.

[54] Shi Z, Li Q, Mei L. pH-sensitive nanoscale materials as robust drug delivery systems for cancer therapy. Chin Chem Lett. 2020; 31(6): 1345-1356.

[55] Ding H, Tan P, Fu S, et al. Preparation and application of pH-responsive drug delivery systems. J Control Release. 2022; 348: 206-238.

[56] Huang Y, Lu Y, Chen J. Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy. J Magn Mater. 2017; 427: 34-40.

[57] Chuang C, Lan Y, Lu Y, Weng Y, Chen J. Targeted delivery of irinotecan and SLP2 shRNA with GRP-conjugated magnetic graphene oxide for glioblastoma treatment. Biomater Sci. 2022; 10(12): 3201-3222.

[58] Li Z, Liu Y, Wang X, et al. One-pot construction of functional mesoporous silica nanoparticles for the tumor-acidity-activated synergistic chemotherapy of glioblastoma. ACS Appl Mater Interfaces. 2013; 5(16): 7995-8001.

[59] Mohamed MS, Veeranarayanan S, Poulose AC, et al. Type 1 ribotoxin-curcin conjugated biogenic gold nanoparticles for a multimodal therapeutic approach towards brain cancer. BBA-Gen Subjects. 2014; 1840(6): 1657-1669.

[60] Ruan S, Yuan M, Zhang L, et al. Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles. Biomaterials. 2015; 37: 425-435.

[61] Pandey A, Singh K, Subramanian S, Korde A, Singh R, Sawant K. Heterogeneous surface architectured pH responsive metal-drug nano-conjugates for mitochondria targeted therapy of glioblastomas: a multimodal intranasal approach. Chem Eng J. 2020; 394: 124419.

[62] Knezevic NZ, Ilic N, Kaluderovic GN. Mesoporous silica nanoparticles for pH-responsive delivery of iridium metallotherapeutics and treatment of glioblastoma multiforme. Inorganics. 2022; 10(12): 250.

[63] Wu H, Lu H, Xiao W, et al. Sequential targeting in crosslinking nanotheranostics for tackling the multibarriers of brain tumors. Adv Mater. 2020; 32(14): 1903759.

[64] Norouzi M, Yathindranath V, Thliveris JA, Miller DW. Salinomycin-loaded iron oxide nanoparticles for glioblastoma therapy. Nanomaterials. 2020; 10(3): 477.

[65] Xie R, Wang Y, Tong F, et al. Hsp70-targeting and size-tunable nanoparticles combine with PD-1 checkpoint blockade to treat glioma. Small. 2023; 19(37).

[66] Cao H, Yang Y, Chen X, Shao Z. Intelligent Janus nanoparticles for intracellular real-time monitoring of dual drug release. Nanoscale. 2016; 8(12): 6754-6760.

[67] Wang Y, Zhang L, Zhang X, Wei X, Tang Z, Zhou S. Precise polymerization of a highly tumor microenvironment-responsive nanoplatform for strongly enhanced intracellular drug release. ACS Appl Mater Interfaces. 2016; 8(9): 5833-5846.

[68] Tao Y, Zheng D, Zhao J, et al. Self-assembling pH-responsive nanoparticle platform based on pectin-doxorubicin conjugates for codelivery of anticancer drugs. ACS Omega. 2021; 6(15): 9998-10004.

[69] Liang H, Zhou B, Wu D, Li J, Li B. Supramolecular design and applications of polyphenol-based architecture: a review. Adv Colloid Interface Sci. 2019; 272: 102019.

[70] Chen X, Fan X, Zhang Y, et al. Cooperative coordination-mediated multi-component self-assembly of “all-in-one” nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer. Acta Pharm Sin B. 2022; 12(9): 3710-3725.

[71] Yang Y, Zhu W, Dong Z, et al. 1D coordination polymer nanofibers for low-temperature photothermal therapy. Adv Mater. 2017; 29(40): 1703588.

[72] Wang H, Zuo Z, Du J, et al. Surface charge critically affects tumor penetration and therapeutic efficacy of cancer nanomedicines. Nano Today. 2016; 11(2): 133-144.

[73] Yuan Y, Ding D, Li K, Liu J, Liu B. Tumor-responsive fluorescent light-up probe based on a gold nanoparticle/conjugated polyelectrolyte hybrid. Small. 2014; 10(10): 1967-1975.

[74] Piao J, Gao F, Li Y, et al. pH-sensitive zwitterionic coating of gold nanocages improves tumor targeting and photothermal treatment efficacy. Nano Res. 2018; 11(6): 3193-3204.

[75] Ofridam F, Tarhini M, Lebaz N, Gagniere E, Mangin D, Elaissari A. pH-sensitive polymers: classification and some fine potential applications. Polym Adv Technol. 2021; 32(4): 1455-1484.

[76] Desai N, Rana D, Salave S, et al. Chitosan: a potential biopolymer in drug delivery and biomedical applications. Pharmaceutics. 2023; 15(4): 1313.

[77] Lou J, Duan H, Qin Q, et al. Advances in oral drug delivery systems: challenges and opportunities. Pharmaceutics. 2023; 15(2): 484.

[78] Liu L, Yao W, Rao Y, Lu X, Gao J. pH-responsive carriers for oral drug delivery: challenges and opportunities of current platforms. Drug Deliv. 2017; 24(1): 569-581.

[79] Han L, Zhang X, Wang Y, et al. Redox-responsive theranostic nanoplatforms based on inorganic nanomaterials. J Control Release. 2017; 259: 40-52.

[80] Hsu P-H, Almutairi A. Recent progress of redox-responsive polymeric nanomaterials for controlled release. J Mater Chem B. 2021; 9(9): 2179-2188.

[81] Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009; 8(7): 579-591.

[82] Gorrini C, Harris IS, Mak TW. Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov. 2013; 12(12): 931-947.

[83] Lapenna D. Glutathione and glutathione-dependent enzymes: from biochemistry to gerontology and successful aging. Ageing Res Rev. 2023; 92: 102066.

[84] Chen B, Dai W, He B, et al. Current multistage drug delivery systems based on the tumor microenvironment. Theranostics. 2017; 7(3): 538-558.

[85] Liu D, Cheng Y, Qiao S, et al. Nano-codelivery of temozolomide and siPD-L1 to reprogram the drug-resistant and immunosuppressive microenvironment in orthotopic glioblastoma. ACS Nano. 2022; 16(5): 7409-7427.

[86] An R, Liu L, Wei S, et al. Controlling disassembly of paramagnetic prodrug and photosensitizer nanoassemblies for on-demand orthotopic glioma theranostics. ACS Nano. 2022; 16(12): 20607-20621.

[87] Xiao T, He M, Xu F, et al. Macrophage membrane-camouflaged responsive polymer nanogels enable magnetic resonance imaging-guided chemotherapy/chemodynamic therapy of orthotopic glioma. ACS Nano. 2021; 15(12): 20377-20390.

[88] Zhang L, Li X, Zhao H, Li M, Li Z. Influence of glutathione responsive tumor-targeted camptothecin nanoparticles on glioma based on oxidative stress. Colloid Interfac Sci. 2021; 42: 100423.

[89] Guo X, Cheng Y, Zhao X, Luo Y, Chen J, Yuan W. Advances in redox-responsive drug delivery systems of tumor microenvironment. J Nanobiotechnol. 2018; 16: 74.

[90] Lee MH, Yang Z, Lim CW, et al. Disulfide-cleavage-triggered chemosensors and their biological applications. Chem Rev. 2013; 113(7): 5071-5109.

[91] Lv L, Li X, Qian W, et al. Enhanced anti-glioma efficacy by borneol combined with CGKRK-modified paclitaxel self-assembled redox-sensitive nanoparticles. Front Pharmacol. 2020; 11: 558.

[92] Zhuo W, Wang W, Zhou W, et al. A targeted and responsive nanoprodrug delivery system for synergistic glioma chemotherapy. Small. 2024:e2400630.

[93] Hao Y, Chen Y, He X, et al. RGD peptide modified platinum nanozyme Co-loaded glutathione-responsive prodrug nanoparticles for enhanced chemo-photodynamic bladder cancer therapy. Biomaterials. 2023; 293: 121975.

[94] Hao C, Shao Y, Tian J, Song J, Song F. Dual-responsive hollow mesoporous organosilicon nanocarriers for photodynamic therapy. J Colloid Interface Sci. 2024; 659: 582-593.

[95] Lee SH, Gupta MK, Bang JB, Bae H, Sung H-J. Current progress in reactive oxygen species (ROS)-responsive materials for biomedical applications. Adv Healthc Mater. 2013; 2(6): 908-915.

[96] Shi Z, Yang J, Liu L, et al. A reactive oxygen species-responsive poly(amino acids) nanoparticle loading doxorubicin for glioblastoma multiforme treatment. J Biomed Nanotechnol. 2020; 16(6): 931-940.

[97] Wu P, Dong W, Guo X, et al. ROS-responsive blended nanoparticles: cascade-amplifying synergistic effects of sonochemotherapy with on-demand boosted drug release during SDT process. Adv Healthc Mater. 2019; 8(18): e1900720.

[98] Zheng M, Liu Y, Wang Y, et al. ROS-responsive polymeric siRNA nanomedicine stabilized by triple interactions for the robust glioblastoma combinational RNAi therapy. Adv Mater. 2019; 31(37): 1903277.

[99] Yang T, Zhang X, Yang X, et al. A mitochondria-targeting self-assembled carrier-free lonidamine nanodrug for redox-activated drug release to enhance cancer chemotherapy. J Mater Chem B. 2023; 11(17): 3951-3957.

[100] Li J, Ding Z, Li Y, et al. Reactive oxygen species-sensitive thioketal-linked mesoporous silica nanoparticles as drug carrier for effective antibacterial activity. Mater Design. 2020; 195: 109021.

[101] Xia X, Yang X, Huang P, Yan D. ROS-responsive nanoparticles formed from RGD-epothilone B conjugate for targeted cancer therapy. ACS Appl Mater Interfaces. 2020; 12(16): 18301-18308.

[102] Chen D, Zhang G, Li R, et al. Biodegradable, hydrogen peroxide, and glutathione dual responsive nanoparticles for potential programmable paclitaxel release. J Am Chem Soc. 2018; 140(24): 7373-7376.

[103] Su X, Zhuang W, Yu T, et al. ROS and GSH dual-responsive GEM prodrug micelles for ROS-triggered fluorescence turn on bioimaging and cancer therapy. Adv Mater Interfaces. 2020; 7(13): 2000294.

[104] Jiang S, Li X, Zhang F, et al. Manganese dioxide-based nanocarrier delivers paclitaxel to enhance chemotherapy against orthotopic glioma through hypoxia relief. Small Methods. 2022; 6(7): 2101531.

[105] Fu C, Duan X, Cao M, et al. Targeted magnetic resonance imaging and modulation of hypoxia with multifunctional hyaluronic acid-MnO₂ nanoparticles in glioma. Adv Healthc Mater. 2019; 8(10): 1900047.

[106] Meng L, Wang C, Lu Y, et al. Targeted regulation of blood-brain barrier for enhanced therapeutic efficiency of hypoxia-modifier nanoparticles and immune checkpoint blockade antibodies for glioblastoma. ACS Appl Mater Interfaces. 2021; 13(10): 11657-11671.

[107] Dong C, Huang Q, Cheng H, et al. Neisseria meningitidis Opca protein/MnO₂ hybrid nanoparticles for overcoming the blood-brain barrier to treat glioblastoma. Adv Mater. 2022; 34(12): 2109213.

[108] de la Rica R, Aili D, Stevens MM. Enzyme-responsive nanoparticles for drug release and diagnostics. Adv Drug Del Rev. 2012; 64(11): 967-978.

[109] Mu J, Lin J, Huang P, Chen X. Development of endogenous enzyme-responsive nanomaterials for theranostics. Chem Soc Rev. 2018; 47(15): 5554-5573.

[110] Hu Q, Katti PS, Gu Z. Enzyme-responsive nanomaterials for controlled drug delivery. Nanoscale. 2014; 6(21): 12273-12286.

[111] Son J, Parveen S, Macpherson D, Marciano Y, Huang RH, Ulijn RV. MMP-responsive nanomaterials. Biomater Sci. 2023; 11(19): 6457-6479.

[112] Son J, Kalafatovic D, Kumar M, et al. Customizing morphology, size, and response kinetics of matrix metalloproteinase-responsive nanostructures by systematic peptide design. ACS Nano. 2019; 13(2): 1555-1562.

[113] Chen A, Lu H, Cao R, et al. A novel MMP-responsive nanoplatform with transformable magnetic resonance property for quantitative tumor bioimaging and synergetic chemo-photothermal therapy. Nano Today. 2022; 45: 101524.

[114] Guo F, Jiao Y, Du Y, et al. Enzyme-responsive nano-drug delivery system for combined antitumor therapy. Int J Biol Macromol. 2022; 220: 1133-1145.

[115] Bruun J, Larsen TB, Jolck RI, et al. Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood-brain barrier and glioma cells. Int J Nanomed. 2015; 10: 5995-6008.

[116] Yao Q, Kou L, Tu Y, Zhu L. MMP-responsive ‘smart’ drug delivery and tumor targeting. Trends Pharmacol Sci. 2018; 39(8): 766-781.

[117] Xu Y, Zhang J, Liu X, et al. MMP-2-responsive gelatin nanoparticles for synergistic tumor therapy. Pharm Dev Technol. 2019; 24(8): 1002-1013.

[118] Yuba E. Development of functional liposomes by modification of stimuli-responsive materials and their biomedical applications. J Mater Chem B. 2020; 8(6): 1093-1107.

[119] Nastyshyn S, Stetsyshyn Y, Raczkowska J, et al. Temperature-responsive polymer brush coatings for advanced biomedical applications. Polymers. 2022; 14(19): 4245.

[120] Strong LE, West JL. Thermally responsive polymer-nanoparticle composites for biomedical applications. Wires Nanomed Nanobi. 2011; 3(3): 307-317.

[121] Qiao S, Wang H. Temperature-responsive polymers: synthesis, properties, and biomedical applications. Nano Res. 2018; 11(10): 5400-5423.

[122] Sanchez-Moreno P, de Vicente J, Nardecchia S, Marchal JA, Boulaiz H. Thermo-sensitive nanomaterials: recent advance in synthesis and biomedical applications. Nanomaterials. 2018; 8(11): 935.

[123] Wu D, Tang Y, Li W, et al. Thermo-sensitive micelles extend therapeutic potential for febrile seizures. Signal Transduct Tar. 2021; 6(1): 296.

[124] Chen R, Romero G, Christiansen MG, Mohr A, Anikeeva P. Wireless magnetothermal deep brain stimulation. Science. 2015; 347(6229): 1477-1480.

[125] Christiansen MG, Senko AW, Anikeeva P. Magnetic strategies for nervous system control. In: Roska B, Zoghbi HY, eds. Annu Rev Neurosci. 2019: 271-+. Annual Review of Neuroscience.

[126] Moon J, Christiansen MG, Rao S, et al. Magnetothermal multiplexing for selective remote control of cell signaling. Adv Funct Mater. 2020; 30(36): 2000577.

[127] Chertok B, David AE, Yang VC. Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration. Biomaterials. 2010; 31(24): 6317-6324.

[128] Chertok B, David AE, Yang VC. Magnetically-enabled and MR-monitored selective brain tumor protein delivery in rats via magnetic nanocarriers. Biomaterials. 2011; 32(26): 6245-6253.

[129] Jhaveri A, Deshpande P, Torchilin V. Stimuli-sensitive nanopreparations for combination cancer therapy. J Control Release. 2014; 190: 352-370.

[130] Lipsman N, Meng Y, Bethune AJ, et al. Blood-brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound. Nat Commun. 2018; 9: 2336.

[131] Fan C-H, Ting C-Y, Chang Y-C, Wei K-C, Liu H-L, Yeh C-K. Drug-loaded bubbles with matched focused ultrasound excitation for concurrent blood-brain barrier opening and brain-tumor drug delivery. Acta Biomater. 2015; 15: 89-101.

[132] Fadera S, Chen P-Y, Liu H-L, Lee IC. Induction therapy of retinoic acid with a temozolomide-loaded gold nanoparticle-associated ultrasound effect on glioblastoma cancer stem-like colonies. ACS Appl Mater Interfaces. 2021; 13(28): 32845-32855.

[133] Rehman FU, Rauf MA, Ullah S, et al. Ultrasound-activated nano-TiO₂ loaded with temozolomide paves the way for resection of chemoresistant glioblastoma multiforme. Cancer Nanotechnol. 2021; 12(1): 17.

[134] Wang Y, Tang Q, Wu R, et al. Ultrasound-triggered piezocatalysis for selectively controlled NO gas and chemodrug release to enhance drug penetration in pancreatic cancer. ACS Nano. 2023; 17(4): 3557-3573.

[135] Ogawa K, Fuchigami Y, Hagimori M, Fumoto S, Maruyama K, Kawakami S. Ultrasound-responsive nanobubble-mediated gene transfection in the cerebroventricular region by intracerebroventricular administration in mice. Eur J Pharm Biopharm. 2019; 137: 1-8.

[136] Wan Q, Zou C, Hu D, et al. Imaging-guided focused ultrasound-induced thermal and sonodynamic effects of nanosonosensitizers for synergistic enhancement of glioblastoma therapy. Biomater Sci. 2019; 7(7): 3007-3015.

[137] Zhao R, Ning X, Wang M, et al. A ROS-responsive simvastatin Nano-prodrug and its fibronectin-targeted co-delivery system for atherosclerosis treatment. ACS Appl Mater Interfaces. 2022; 14(22): 25080-25092.

[138] Dou Y, Chen Y, Zhang X, et al. Non-proinflammatory and responsive nanoplatforms for targeted treatment of atherosclerosis. Biomaterials. 2017; 143: 93-108.

[139] He J, Zhang W, Zhou X, et al. Reactive oxygen species (ROS)-responsive size-reducible nanoassemblies for deeper atherosclerotic plaque penetration and enhanced macrophage-targeted drug delivery. Bioact Mater. 2023; 19: 115-126.

[140] Mehta S, Bongcaron V, Nguyen TK, et al. An ultrasound-responsive theranostic cyclodextrin-loaded nanoparticle for multimodal imaging and therapy for atherosclerosis. Small. 2022; 18(31): 2200967.

[141] Ma D, Zhuang W, Liu Q, et al. A pH-responsive nanoplatform with aggregation-induced emission features for lipid droplet imaging in atherosclerosis. Chem Eng J. 2023; 476: 146792.

[142] Liu B, Han G-M, Wang D-X, et al. Red blood cell membrane biomimetic nanoprobes for ratiometric imaging of reactive oxygen species level in atherosclerosis. Chem Eng J. 2024; 479: 147515.

[143] Liu J, He Z, Zhong Y, et al. Reactive oxygen species-responsive sequentially targeted AIE fluorescent probe for precisely identifying the atherosclerotic plaques. ACS Appl Mater Interfaces. 2023; 15(40): 47381-47393.

[144] Ye Z, Ji M, Wu K, et al. In-sequence high-specificity dual-reporter unlocking of fluorescent probe enables the precise identification of atherosclerotic plaques. Angew Chem Int Edit. 2022; 61(29): e202204518.

[145] Zhang M, Wang Z, Wang C, Wu Y, Li Z, Liu Z. Visualizing oxidative stress Level for timely assessment of ischemic stroke via a ratiometric near-infrared-II luminescent nanoprobe. ACS Nano. 2021; 15(7): 11940-11952.

[146] Yang H, Jang M-S, Gao G, Lee JH, Lee DS. pH-responsive biodegradable polymeric micelles with anchors to interface magnetic nanoparticles for MR imaging in detection of cerebral ischemic area. Nanoscale. 2016; 8(25): 12588-12598.

[147] Cheng Y, Cheng A, Jia Y, et al. pH-responsive multifunctional theranostic rapamycin-loaded nanoparticles for imaging and treatment of acute ischemic stroke. ACS Appl Mater Interfaces. 2021; 13(48): 56909-56922.

[148] Ma B, Xiao Y, Lv Q, Li G, Wang Y, Fu G. Targeting theranostics of atherosclerosis by dual-responsive nanoplatform via photoacoustic imaging and three-in-one integrated lipid management. Adv Mater. 2023; 35(5): e2206129.

[149] Fang H, Huang L, Lv F, et al. Dual-responsive targeted atherosclerosis therapy through a multi-effective nanoplatform with anti-inflammatory, lipid-regulating and autophagy. Chem Eng J. 2023; 454: 140067.

[150] Xu H, She P, Ma B, Zhao Z, Li G, Wang Y. ROS responsive nanoparticles loaded with lipid-specific AIEgen for atherosclerosis-targeted diagnosis and bifunctional therapy. Biomaterials. 2022; 288: 121734.

[151] Shen M, Jiang H, Li S, et al. Dual-modality probe nanodrug delivery systems with ROS-sensitivity for atherosclerosis diagnosis and therapy. J Mater Chem B. 2024; 12(5): 1344-1354.

[152] Ma B, Xu H, Wang Y, et al. Biomimetic-coated nanoplatform with lipid-specific imaging and ROS responsiveness for atherosclerosis-targeted theranostics. ACS Appl Mater Interfaces. 2021; 13(30): 35410-35421.

[153] Jia H, Zhu Y, Liu X, et al. Construction of dually responsive nanotransformers with nanosphere-nanofiber-nanosphere transition for overcoming the size paradox of anticancer nanodrugs. ACS Nano. 2019; 13(10): 11781-11792.

[154] Ang CY, Tan SY, Teh C, et al. Redox and pH dual responsive polymer based nanoparticles for in vivo drug delivery. Small. 2017; 13(7): 1602379.

[155] Liu Y, Yang Z, Huang X, et al. Glutathione-responsive self-assembled magnetic gold nanowreath for enhanced tumor imaging and imaging-guided photothermal therapy. ACS Nano. 2018; 12(8): 8129-8137.

[156] Zhou F, Yang S, Zhao C, et al. gamma-Glutamyl transpeptidase-activatable near-infrared nanoassembly for tumor fluorescence imaging-guided photothermal therapy. Theranostics. 2021; 11(14): 7045-7056.

[157] Wang P, Shi Y, Zhang S, et al. Hydrogen peroxide responsive iron-based nanoplatform for multimodal imaging-guided cancer therapy. Small. 2019; 15(4): 1803791.

[158] Yang G, Xu L, Chao Y, et al. Hollow MnO₂ as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses. Nat Commun. 2017; 8: 902.

[159] Li L, Lin Z, Xu X, et al. A pH/GSH/glucose responsive nanozyme for tumor cascade amplified starvation and chemodynamic theranostics. ACS Appl Mater Interfaces. 2023; 15(35): 41224-41236.

[160] Cheng G, Zong W, Guo H, et al. Programmed size-changeable nanotheranostic agents for enhanced imaging-guided chemo/photodynamic combination therapy and fast elimination. Adv Mater. 2021; 33(21): 2100398.

[161] Ying X, Wang Y, Liang J, et al. Angiopep-conjugated electro-responsive hydrogel nanoparticles: therapeutic potential for epilepsy. Angew Chem Int Edit. 2014; 53(46): 12436-12440.

[162] Wu D, Fei F, Zhang Q, et al. Nanoengineered on-demand drug delivery system improves efficacy of pharmacotherapy for epilepsy. Sci Adv. 2022; 8(2): eabm3381.

[163] Lu Y, Guo Z, Zhang Y, et al. Microenvironment remodeling micelles for Alzheimer’s disease therapy by early modulation of activated microglia. Adv Sci. 2019; 6(4): 1801586.

[164] Wang S, Sheng Z, Yang Z, et al. Activatable small-molecule photoacoustic probes that cross the blood-brain barrier for visualization of copper(II) in mice with Alzheimer’s disease. Angew Chem Int Edit. 2019; 58(36): 12415-12419.

[165] Miao J, Miao M, Jiang Y, et al. An activatable NIR-II fluorescent reporter for in vivo imaging of amyloid-β plaques. Angew Chem Int Edit. 2023; 62(7): e202216351.

[166] Tan J, Duan X, Zhang F, et al. Theranostic nanomedicine for synergistic chemodynamic therapy and chemotherapy of orthotopic glioma. Adv Sci. 2020; 7(24): 2003036.

[167] Zhang Q, Yang L, Zheng Y, et al. Electro-responsive micelle-based universal drug delivery system for on-demand therapy in epilepsy. J Control Release. 2023; 360: 759-771.

[168] Sun Q, Luan L, Arif M, et al. Redox-sensitive nanoparticles based on 4-aminothiophenol-carboxymethyl inulin conjugate for budesonide delivery in inflammatory bowel diseases. Carbohydr Polym. 2018; 189: 352-359.

[169] Yu M, Chang C-Y, Chao Y, et al. pH-responsive hydrogel with an anti-glycation agent for modulating experimental periodontitis. J Periodontol. 2016; 87(6): 742-748.

[170] Liu Q, Zhong Y, Su Y, Zhao L, Peng J. Real-time imaging of hepatic inflammation using hydrogen sulfide-activatable second near-infrared luminescent nanoprobes. Nano Lett. 2021; 21(11): 4606-4614.

[171] Jing F, Zhu Y, Li F, et al. Bimetallic ions-doped carbon dots nanotheranostics for imaging-guided macrophage polarization/ROS scavenging in acute pancreatitis. Chem Eng J. 2023; 465: 142675.

[172] Lan Q, Lu R, Chen H, et al. MMP-13 enzyme and pH responsive theranostic nanoplatform for osteoarthritis. J Nanobiotechnol. 2020; 18(1): 117.

[173] Ma B, Xu H, Zhuang W, Wang Y, Li G, Wang Y. Reactive oxygen species responsive theranostic nanoplatform for two-photon aggregation-induced emission imaging and therapy of acute and chronic inflammation. ACS Nano. 2020; 14(5): 5862-5873.

[174] Sun R, Wang L, Shi D, Wang H, Song L. pH-activated antibacterial coating switching from polyzwitterion to polycation. Prog Org Coat. 2024; 186: 108060.

[175] Zhang Y, Yue T, Gu W, et al. pH-responsive hierarchical H₂S-releasing nano-disinfectant with deep-penetrating and anti-inflammatory properties for synergistically enhanced eradication of bacterial biofilms and wound infection. J Nanobiotechnol. 2022; 20(1): 55.

[176] Zhang S, Hussain S, Tang Y, et al. Enzyme-triggered on-demand release of a H₂O₂-self-supplying CuO2@Fe3O4 nanoagent for enhanced chemodyamic antimicrobial therapy and wound healing. J Mater Chem B. 2024; 12(14): 3404-3416.

[177] Zhao Y, Zhu Y, Yang G, et al. A pH/H₂O₂ dual triggered nanoplatform for enhanced photodynamic antibacterial efficiency. J Mater Chem B. 2021; 9(25): 5076-5082.

[178] Xie X, Sun T, Xue J, et al. Ag nanoparticles cluster with pH-triggered reassembly in targeting antimicrobial applications. Adv Funct Mater. 2020; 30(17): 2000511.

[179] Harris M, Ahmed H, Barr B, et al. Magnetic stimuli-responsive chitosan-based drug delivery biocomposite for multiple triggered release. Int J Biol Macromol. 2017; 104: 1407-1414.

[180] Li L, Liu M, Deng S, Zhu X, Song Y, Song E. A pH-responsive magnetic resonance tuning probe for precise imaging of bacterial infection in vivo. Acta Biomater. 2023; 164: 487-495.

[181] Li L, Liu M, Deng S, Zhu X, Song Y, Song E. Enzyme-triggered transforming of assembly peptide-modified magnetic resonance-tuned probe for highly sensitive imaging of bacterial infection in vivo. Small. 2023; 19(25): 202208249.

[182] Liu P, Xu LQ, Xu G, Pranantyo D, Neoh K-G, Kang E-T. pH-sensitive theranostic nanoparticles for targeting bacteria with fluorescence imaging and dual-modal antimicrobial therapy. ACS Appl Nano Mater. 2018; 1(11): 6187-6196.

[183] Mao D, Hu F, Kenry , et al. Metal-organic-framework-assisted in vivo bacterial metabolic labeling and precise antibacterial therapy. Adv Mater. 2018; 30(18): 1706831.

[184] Xiu W, Gan S, Wen Q, et al. Biofilm microenvironment-responsive nanotheranostics for dual-mode imaging and hypoxia-relief-enhanced photodynamic therapy of bacterial infections. Research. 2020; 2020:Unsp 9426453.

[185] Yuwen L, Qiu Q, Xiu W, et al. Hyaluronidase-responsive phototheranostic nanoagents for fluorescence imaging and photothermal/photodynamic therapy of methicillin-resistant Staphylococcus aureus infections. Biomater Sci. 2021; 9(12): 4484-4495.

[186] Wang B, Yan L, Chen L, Zhao X, Yan X. Responsive nanoplatform for persistent luminescence “turn-on” imaging and “on-demand” synergistic therapy of bacterial infection. J Colloid Interface Sci. 2022; 610: 687-697.

[187] Yan L, Chen L, Zhao X, Yan X. pH switchable nanoplatform for in vivo persistent luminescence imaging and precise photothermal therapy of bacterial infection. Adv Funct Mater. 2020; 30(14): 1909042.

[188] Kim H, Kim S, Baek SH, Kwon S-M. Pivotal cytoprotective mediators and promising therapeutic strategies for endothelial progenitor cell-based cardiovascular regeneration. Stem Cells Int. 2016; 2016: 8340257.

[189] Bjoerkegren JLM, Lusis AJ. Atherosclerosis: recent developments. Cell. 2022; 185(10): 1630-1645.

[190] Suarez S, Almutairi A, Christman KL. Micro-and nanoparticles for treating cardiovascular disease. Biomater Sci. 2015; 3(4): 564-580.

[191] Cicha I, Singh R, Garlichs CD, Alexiou C. Nano-biomaterials for cardiovascular applications: clinical perspective. J Control Release. 2016; 229: 23-36.

[192] Deng Y, Zhang X, Shen H, et al. Application of the nano-drug delivery system in treatment of cardiovascular diseases. Front Bioeng Biotech. 2020; 7: 489.

[193] Wei C, Jiang Z, Li C, Li P, Fu Q. Nanomaterials responsive to endogenous biomarkers for cardiovascular disease theranostics. Adv Funct Mater. 2023; 33(26): 2214655.

[194] Mahmoudpour M, Ding S, Lyu Z, et al. Aptamer functionalized nanomaterials for biomedical applications: recent advances and new horizons. Nano Today. 2021; 39: 101177.

[195] Heo J, Kang H. Exosome-based treatment for atherosclerosis. Int J Mol Sci. 2022; 23(2): 1002.

[196] Engelen SE, Robinson AJB, Zurke Y-X, Monaco C. Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed? Nat Rev Cardiol. 2022; 19(8): 522-542.

[197] Xiao Z, Li Y, Xiong L, et al. Recent advances in anti-atherosclerosis and potential therapeutic targets for nanomaterial-derived drug formulations. Adv Sci. 2023; 10(29): e2302918.

[198] Perera B, Wu Y, Nguyen N-T, Ta HT. Advances in drug delivery to atherosclerosis: investigating the efficiency of different nanomaterials employed for different type of drugs. Mater Today Bio. 2023; 22: 100767.

[199] Rumanti AP, Maruf A, Liu H, Ge S, Lei D, Wang G. Engineered bioresponsive nanotherapeutics: recent advances in the treatment of atherosclerosis and ischemic-related disease. J Mater Chem B. 2021; 9(24): 4804-4825.

[200] Maruf A, Wang Y, Yin T, et al. Atherosclerosis treatment with stimuli-responsive nanoagents: recent advances and future perspectives. Adv Healthc Mater. 2019; 8(11): 1900036.

[201] Song Y, Jing H, Vong LB, Wang J, Li N. Recent advances in targeted stimuli-responsive nano-based drug delivery systems combating atherosclerosis. Chin Chem Lett. 2022; 33(4): 1705-1717.

[202] Saxer T, Zumbuehl A, Mueller B. The use of shear stress for targeted drug delivery. Cardiovasc Res. 2013; 99(2): 328-333.

[203] Wang Y, Pisapati AV, Zhang XF, Cheng X. Recent developments in nanomaterial-based shear-sensitive drug delivery systems. Adv Healthc Mater. 2021; 10(13): 2002196.

[204] Holme MN, Fedotenko IA, Abegg D, et al. Shear-stress sensitive lenticular vesicles for targeted drug delivery. Nat Nanotechnol. 2012; 7(8): 536-543.

[205] Wang J, Lu B, Yin G, et al. Design and fabrication of environmentally responsive nanoparticles for the diagnosis and treatment of atherosclerosis. ACS Biomater Sci Eng. 2024; 10(3): 1190-1206.

[206] Shen M, Jiang H, Zhao Y, et al. Shear stress and ROS dual-responsive RBC-hitchhiking nanoparticles for atherosclerosis therapy. ACS Appl Mater Interfaces. 2023; 15(37): 43374-43386.

[207] Libby P, Buring JE, Badimon L, et al. Atherosclerosis. Nat Rev Dis Primers. 2019; 5(1): 56.

[208] Setia A, Mehata AK, Priya V, et al. Current advances in nanotheranostics for molecular imaging and therapy of cardiovascular disorders. Mol Pharm. 2023; 20(10): 4922-4941.

[209] Li X, Su F, Yuan Q, Chen Y, Liu C-Y, Fan Y. Advances in differential diagnosis of cerebrovascular diseases in magnetic resonance imaging: a narrative review. Quant Imag Med Surg. 2023; 13(4): 2712-2734.

[210] Jafari M, Shoeibi A, Khodatars M, et al. Automated diagnosis of cardiovascular diseases from cardiac magnetic resonance imaging using deep learning models: a review. Comput Biol Med. 2023; 160: 106998.

[211] Li S, Zhuang W, Chen J, et al. A lipid droplets specific probe for imaging of atherosclerosis and fibrocalcific bicuspid aortic valves. Sensor Actuat B Chem. 2021; 346: 130458.

[212] Chen J, Li S, Ma D, Li L, Zhuang W, Chen M. A lipid droplet-specific fluorescence probe for atherosclerotic plaque imaging. Analyst. 2022; 147(13): 3081-3086.

[213] Zheng Y, Zhou Z, Han F, Chen Z. Special issue: neuroinflammatory pathways as treatment targets in brain disorders autophagic regulation of neuroinflammation in ischemic stroke. Neurochem Int. 2021; 148: 105114.

[214] von Hanwehr R, Smith ML, Siesjo BK. Extra-and intracellular pH during near-complete forebrain ischemia in the rat. J Neurochem. 1986; 46(2): 331-339.

[215] Melzer S, Ankri R, Fixler D, Tarnok A. Nanoparticle uptake by macrophages in vulnerable plaques for atherosclerosis diagnosis. J Biophotonics. 2015; 8(11-12): 871-883.

[216] Zhang S, Liu Y, Cao Y, et al. Targeting the microenvironment of vulnerable atherosclerotic plaques: an emerging diagnosis and therapy strategy for atherosclerosis. Adv Mater. 2022; 34(29): 2110660.

[217] Zhang Y, Gong F, Wu Y, et al. Poly-β-cyclodextrin supramolecular nanoassembly with a pH-sensitive switch removing lysosomal cholesterol crystals for antiatherosclerosis. Nano Lett. 2021; 21(22): 9736-9745.

[218] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74(3): 229-263.

[219] Paskeh MDA, Entezari M, Mirzaei S, et al. Emerging role of exosomes in cancer progression and tumor microenvironment remodeling. J Hematol Oncol. 2022; 15(1): 83.

[220] Li B, Shao H, Gao L, Li H, Sheng H, Zhu L. Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: a review. Drug Deliv. 2022; 29(1): 2130-2161.

[221] Saltzman , Fung . Polymeric implants for cancer chemotherapy. Adv Drug Del Rev. 1997; 26(2-3): 209-230.

[222] Gao Y, Wang K, Zhang J, Duan X, Sun Q, Men K. Multifunctional nanoparticle for cancer therapy. MedComm. 2023; 4(1): e187-e187.

[223] He Q, Chen J, Yan J, et al. Tumor microenvironment responsive drug delivery systems. Asian J Pharm Sci. 2020; 15(4): 416-448.

[224] Singh R, Sharma A, Saji J, Umapathi A, Kumar S, Daima HK. Smart nanomaterials for cancer diagnosis and treatment. Nano Converg. 2022; 9(1): 21.

[225] Cheng G, Wu D, Wang S, et al. Stimuli-responsive size-changeable strategy for cancer theranostics. Nano Today. 2021; 38: 101208.

[226] Cheng P, Pu K. Activatable phototheranostic materials for imaging-guided cancer therapy. ACS Appl Mater Interfaces. 2020; 12(5): 5286-5299.

[227] Zhang P, Zhu Y, Xiao C, Chen X. Activatable dual-functional molecular agents for imaging-guided cancer therapy. Adv Drug Del Rev. 2023; 195: 114725.

[228] Zhou Y, Li Q, Wu Y, et al. Molecularly stimuli-responsive self-assembled peptide nanoparticles for targeted imaging and therapy. ACS Nano. 2023; 17(9): 8004-8025.

[229] Zhang W, Gao C. Recent advances in cell imaging and cytotoxicity of intracellular stimuli-responsive nanomaterials. Sci Bull. 2015; 60(23): 1973-1979.

[230] Wang X, Shan M, Zhang S, et al. Stimuli-responsive antibacterial materials: molecular structures, design principles, and biomedical applications. Adv Sci. 2022; 9(13): 2104843.

[231] Feng L, Dong Z, Tao D, Zhang Y, Liu Z. The acidic tumor microenvironment: a target for smart cancer nano-theranostics. Natl Sci Rev. 2018; 5(2): 269-286.

[232] Wang S, Hou Y. New types of magnetic nanoparticles for stimuli-responsive theranostic nanoplatforms. Adv Sci. 2024; 11(8): e2305459.

[233] Yao X, Mu J, Zeng L, et al. Stimuli-responsive cyclodextrin-based nanoplatforms for cancer treatment and theranostics. Mater Horiz. 2019; 6(5): 846-870.

[234] Feigin VL, Vos T, Nichols E, et al. The global burden of neurological disorders: translating evidence into policy. Lancet Neurol. 2020; 19(3): 255-265.

[235] Silberberg D, Anand NP, Michels K, Kalaria RN. Brain and other nervous system disorders across the lifespan - global challenges and opportunitiesINTRODUCTION. Nature. 2015; 527(7578): S151-S154.

[236] Kanwar JR, Sriramoju B, Kanwar RK. Neurological disorders and therapeutics targeted to surmount the blood-brain barrier. Int J Nanomed. 2012; 7: 3259-3278.

[237] Meng L, Ren N, Dong M, et al. Metal-organic frameworks for nerve repair and neural stem cell therapy. Adv Funct Mater. 2024; 34(3): 2309974.

[238] Zou Y, Liu Y, Yang Z, et al. Effective and targeted human orthotopic glioblastoma xenograft therapy via a multifunctional biomimetic nanomedicine. Adv Mater. 2018; 30(51): 1803717.

[239] Hernandez-Pedro NY, Rangel-Lopez E, Magana-Maldonado R, et al. Application of nanoparticles on diagnosis and therapy in gliomas. Biomed Res Int. 2013; 2013: 351031.

[240] Ozdemir-Kaynak E, Qutub AA, Yesil-Celiktas O. Advances in glioblastoma multiforme treatment: new models for nanoparticle therapy. Front Physiol. 2018; 9: 170.

[241] Di Filippo LD, Duarte JL, Luiz MT, Cavalcante de Araujo JT, Chorilli M. Drug delivery nanosystems in glioblastoma multiforme treatment: current state of the art. Curr Neuropharmacol. 2021; 19(6): 787-812.

[242] Hsu J-F, Chu S-M, Liao C-C, et al. Nanotechnology and nanocarrier-based drug delivery as the potential therapeutic strategy for glioblastoma multiforme: an update. Cancers. 2021; 13(2): 195.

[243] Karim R, Palazzo C, Evrard B, Piel G. Nanocarriers for the treatment of glioblastoma multiforme: current state-of-the-art. J Control Release. 2016; 227: 23-37.

[244] Ding D, Zhou D, Sander JW, Wang W, Li S, Hong Z. Epilepsy in China: major progress in the past two decades. Lancet Neurol. 2021; 20(4): 316-326.

[245] Wang Y, Ying X, Chen L, et al. Electroresponsive nanoparticles improve antiseizure effect of phenytoin in generalized tonic-clonic seizures. Neurotherapeutics. 2016; 13(3): 603-613.

[246] Wang X, Zhang M, Li Y, Cong H, Yu B, Shen Y. Research status of dendrimer micelles in tumor therapy for drug delivery. Small. 2023; 19(50): e2304006.

[247] Eleftheriadou D, Kesidou D, Moura F, Felli E, Song W. Redox-responsive nanobiomaterials-based therapeutics for neurodegenerative diseases. Small. 2020; 16(43): 1907308.

[248] Liang F, You Q, Ma X, et al. Nano-imaging agents for brain diseases: environmentally responsive imaging and therapy. Nano Res. 2023; 16(12): 13134-13163.

[249] Rodrigues AF, Rebelo C, Reis T, et al. Engineering optical tools for remotely controlled brain stimulation and regeneration. Biomater Sci. 2023; 11(9): 3034-3050.

[250] Hadavi D, Poot AA. Biomaterials for the treatment of Alzheimer’s disease. Front Bioeng Biotech. 2016; 4: 49.

[251] Fu Q, Yu L, Wang Y, Li P, Song J. Biomarker-responsive nanosystems for chronic disease theranostics. Adv Funct Mater. 2023; 33(2): 2206300.

[252] Knopman DS, Amieva H, Petersen RC, et al. Alzheimer disease. Nat Rev Dis Primers. 2021; 7(1): 33.

[253] Handa M, Singh A, Flora SJS, Shukla R. Stimuli-responsive polymeric nanosystems for therapeutic applications. Curr Pharm Des. 2022; 28(11): 910-921.

[254] Kimura H. Signaling of hydrogen sulfide and polysulfides. Antioxid Redox Signal. 2015; 22(5): 347-349.

[255] Zhao X, Ding M, Ning L, et al. Biothiol-triggered H2S release from a near-infrared fluorescent H2S donor promotes cutaneous wound healing. Acta Materia Medica. 2022; 1(4): 476-485.

[256] Zou J, Yuan Z, Chen X, et al. Hydrogen sulfide responsive nanoplatforms: novel gas responsive drug delivery carriers for biomedical applications. Asian J Pharm Sci. 2024; 19(1): 100858.

[257] He S, Chen S, Li D, et al. High affinity to skeleton rare earth doped nanoparticles for near-infrared II imaging. Nano Lett. 2019; 19(5): 2985-2992.

[258] Dunlop DD, Manheim LM, Song J, Chang RW. Arthritis prevalence and activity limitations in older adults. Arthritis Rheum. 2001; 44(1): 212-221.

[259] Rousseau J-C, Delmas PD. Biological markers in osteoarthritis. Nat Clin Pract Rheumatol. 2007; 3(6): 346-356.

[260] Meng F, Zhang Z, Chen W, et al. MicroRNA-320 regulates matrix metalloproteinase-13 expression in chondrogenesis and interleukin-1β-induced chondrocyte responses. Osteoarthritis Cartilage. 2016; 24(5): 932-941.

[261] Zou Z, Li H, Yu K, et al. The potential role of synovial cells in the progression and treatment of osteoarthritis. Exploration (Beijing, China). 2023; 3(5): 20220132.

[262] Helmchen F, Denk W. Deep tissue two-photon microscopy. Nat Methods. 2005; 2(12): 932-940.

[263] Theer P, Hasan MT, Denk W. Two-photon imaging to a depth of 1000 microm in living brains by use of a Ti:Al₂O₃ regenerative amplifier. Opt Lett. 2003; 28(12): 1022-1024.

[264] Wu Z, Nie R, Wang Y, Wang Q, Li X, Liu Y. Precise antibacterial therapeutics based on stimuli-responsive nanomaterials. Front Bioeng Biotech. 2023; 11: 1289323.

[265] Geng Z, Cao Z, Liu J. Recent advances in targeted antibacterial therapy basing on nanomaterials. Exploration (Beijing, China). 2023; 3(1): 20210117.

[266] Yang Y, Jiang X, Lai H, Zhang X. Smart bacteria-responsive drug delivery systems in medical implants. J Functl Biomater. 2022; 13(4): 173.

[267] Huang Y, Zou L, Wang J, Jin Q, Ji J. Stimuli-responsive nanoplatforms for antibacterial applications. Wires Nanomed Nanobi. 2022; 14(3): e1775.

[268] Bag N, Bardhan S, Roy S, et al. Nanoparticle-mediated stimulus-responsive antibacterial therapy. Biomater Sci. 2023; 11(6): 1994-2019.

[269] Canaparo R, Foglietta F, Giuntini F, Della Pepa C, Dosio F, Serpe L. Recent developments in antibacterial therapy: focus on stimuli-responsive drug-delivery systems and therapeutic nanoparticles. Molecules. 2019; 24(10): 1991.

[270] Hu Y, Ruan X, Lv X, et al. Biofilm microenvironment-responsive nanoparticles for the treatment of bacterial infection. Nano Today. 2022; 46: 101602.

[271] Hu Y, Li S, Dong H, et al. Environment-responsive therapeutic platforms for the treatment of implant infection. Adv Healthc Mater. 2023; 12(26): e2300985.

[272] Radovic-Moreno AF, Lu TK, Puscasu VA, Yoon CJ, Langer R, Farokhzad OC. Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted delivery of antibiotics. ACS Nano. 2012; 6(5): 4279-4287.

[273] Lv X, Zhang J, Yang D, et al. Recent advances in pH-responsive nanomaterials for anti-infective therapy. J Mater Chem B. 2020; 8(47): 10700-10711.

[274] Huang H, Ali A, Liu Y, et al. Advances in image-guided drug delivery for antibacterial therapy. Adv Drug Del Rev. 2023; 192: 114634.

[275] Yang S, Song Y, Dong H, et al. Stimuli-actuated turn-on theranostic nanoplatforms for imaging-guided antibacterial treatment. Small. 2023; 19(52): 2304127.

[276] Hoerr V, Faber C. Magnetic resonance imaging characterization of microbial infections. J Pharm Biomed Anal. 2014; 93: 136-146.

[277] Huang L, Fang J, Hong S, et al. MicroPET imaging of bacterial infection with nitroreductase-specific responsive 18F-labelled nitrogen mustard analogues. Eur J Nucl Med Mol Imaging. 2022; 49(8): 2645-2654.

[278] Colino CI, Lanao JM, Gutierrez-Millan C. Recent advances in functionalized nanomaterials for the diagnosis and treatment of bacterial infections. Mat Sci Eng C Mater. 2021; 121: 111843.

[279] Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999; 284(5418): 1318-1322.

[280] Stoodley P, Sauer K, Davies DG, Costerton JW. Biofilms as complex differentiated communities. Annu Rev Microbiol. 2002; 56: 187-209.

[281] Mah TF, O’Toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 2001; 9(1): 34-39.

[282] Xu W, Qing X, Liu S, Chen Z, Zhang Y. Manganese oxide nanomaterials for bacterial infection detection and therapy. J Mater Chem B. 2022; 10(9): 1343-1358.

[283] Borjihan Q, Wu H, Dong A, Gao H, Yang Y-W. AIEgens for bacterial imaging and ablation. Adv Healthc Mater. 2021; 10(24): 2100877.

[284] Li J, Zheng M, Shimoni O, et al. Development of novel therapeutics targeting the blood-brain barrier: from barrier to carrier. Adv Sci. 2021; 8(16): 2101090.

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