Downloads

Peng, X., & Ding, L. Regulating Autophagy in Nanomedicine: Advancing Cancer Therapy. Medical Materials Research. 2025. doi: Retrieved from https://w3.sciltp.com/journals/mmr/article/view/801
Volume 1, Issue 1, 2025
Copyright (c) 2025 by the authors.
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Review

Regulating Autophagy in Nanomedicine: Advancing Cancer Therapy

Xiaoman Peng and Li Ding *

Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai 200072, China

* Correspondence: dingli@tongji.edu.cn

Received: 22 January 2025; Revised: 19 February 2025; Accepted: 20 February 2025; Published: 27 February 2025

Abstract: Autophagy, a cellular process responsible for degrading and recycling damaged organelles and proteins, plays a crucial role in maintaining cellular homeostasis and responding to stress. In cancer therapy, autophagy exhibits dual roles, acting as both a protective mechanism for cancer cells and a therapeutic target. Nanomedicine, with its ability to precisely deliver drugs and modulate biological processes at the cellular level, offers novel opportunities to regulate autophagy and enhance the efficacy of cancer treatments. This review explores the intricate relationship between autophagy and nanomedicine, highlighting how nanoparticles can be engineered to modulate autophagic pathways to either promote cancer cell death or inhibit tumor survival. We discuss various strategies, such as the use of nanocarriers, including nanoparticles, nanocapsules, and nanogels, to selectively target autophagy-related proteins and pathways in cancer cells. Furthermore, the potential of combining autophagy modulation with other therapeutic approaches, including chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), immunotherapy and multiple therapeutics, is examined. Understanding the complex interplay between autophagy and nanomedicine is essential for developing advanced therapeutic strategies that can overcome treatment resistance and improve cancer outcomes. This review provides a comprehensive overview of current advancements and future directions in regulating autophagy in nanomedicine for cancer therapy. 

Keywords:

autophagy nanomedicine cancer therapy

References

  1. Tintelnot, J.; Xu, Y.; Lesker, T.R.; et al. Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer. Nature 2023, 615, 168–174. https://doi.org/10.1038/s41586-023-05728-y.
  2. Liu, S.Z.; Yao, S.J.; Yang, H.; et al. Autophagy: Regulator of cell death. Cell Death Dis. 2023, 14, 648.
  3. Zhang, J.; Xiang, Q.; Wu, M.; et al. Autophagy Regulators in Cancer. Int. J. Mol. Sci. 2023, 24, 10944. https://doi.org/10.3390/ijms241310944.
  4. Debnath, J.; Gammoh, N.; Ryan, K.M. Autophagy and autophagy-related pathways in cancer. Nat. Rev. Mol. Cell Bio 2023, 24, 560–575. https://doi.org/10.1038/s41580-023-00585-z.
  5. Gautam, R.K.; Mittal, P.; Goyal, R.; et al. Nanomedicine: Innovative Strategies and Recent Advances in Targeted Cancer Therapy. Curr. Med. Chem. 2024, 31, 4479–4494. https://doi.org/10.2174/0109298673258987231004092334.
  6. Lin, L.B.; He, W.X.; Guo, Y.X.; et al. Nanomedicine-induced programmed cell death in cancer therapy: Mechanisms and perspectives. Cell Death Discov. 2024, 10, 386.
  7. Yusuf, A.; Almotairy, A.R.Z.; Henidi, H.; et al. Nanoparticles as Drug Delivery Systems: A Review of the Implication of Nanoparticles’ Physicochemical Properties on Responses in Biological Systems. Polymers 2023, 15, 1596. https://doi.org/10.3390/polym15071596.
  8. Zhang, Y.J.; Zhao, J.J.; Zhang, L.M.; et al. A cascade nanoreactor for enhancing sonodynamic therapy on colorectal cancersynergistic ROS augment and autophagy blockage. Nano Today 2023, 49, 101798.
  9. Gao, C.; Kwong, C.H.T.; Wang, Q.; et al. Conjugation of Macrophage-Mimetic Microalgae and Liposome for Antitumor Sonodynamic Immunotherapy via Hypoxia Alleviation and Autophagy Inhibition. ACS Nano 2023, 17, 4034–4049. https://doi.org/10.1021/acsnano.3c00041.
  10. Chen, J.L.; Wu, X.; Yin, D.; et al. Autophagy inhibitors for cancer therapy: Small molecules and nanomedicines. Pharmacol. Ther. 2023, 249, 108485. https://doi.org/10.1016/j.pharmthera.2023.108485.
  11. Huang, Y.Y.; You, X.; Wang, L.N.; et al. Pyridinium-Substituted Tetraphenylethylenes Functionalized with Alkyl Chains as Autophagy Modulators for Cancer Therapy. Angew. Chem. Int. Edit 2020, 59, 10042–10051. https://doi.org/10.1002/anie.202001906.
  12. Zhou, X.; Medina-Ramirez, I.E.; Su, G.; et al. All Roads Lead to Rome: Comparing Nanoparticle- and Small Molecule-Driven Cell Autophagy. Small 2024, 20, e2310966. https://doi.org/10.1002/smll.202310966.
  13. Liu, J.; Cabral, H.; Mi, P. Nanocarriers address intracellular barriers for efficient drug delivery, overcoming drug resistance, subcellular targeting and controlled release. Adv. Drug Deliv. Rev. 2024, 207, 115239. https://doi.org/10.1016/j.addr.2024.115239.
  14. Chehelgerdi, M.; Chehelgerdi, M.; Allela, O.Q.B.; et al. Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation. Mol. Cancer 2023, 22, 169. https://doi.org/10.1186/s12943-023-01865-0.
  15. Beach, M.A.; Nayanathara, U.; Gao, Y.; et al. Polymeric Nanoparticles for Drug Delivery. Chem. Rev. 2024, 124, 5505–5616. https://doi.org/10.1021/acs.chemrev.3c00705.
  16. Meng, Q.; Ding, B.; Ma, P.; et al. Interrelation between Programmed Cell Death and Immunogenic Cell Death: Take Antitumor Nanodrug as an Example. Small Methods 2023, 7, e2201406. https://doi.org/10.1002/smtd.202201406.
  17. Xiao, H.; Li, X.; Li, B.; et al. Nanodrug Inducing Autophagy Inhibition and Mitochondria Dysfunction for Potentiating Tumor Photo-Immunotherapy. Small 2023, 19, e2300280. https://doi.org/10.1002/smll.202300280.
  18. Zhang, X.; Chen, X.; Guo, Y.; et al. Endosome/lysosome-detained supramolecular nanogels as an efflux retarder and autophagy inhibitor for repeated photodynamic therapy of multidrug-resistant cancer. Nanoscale Horiz. 2020, 5, 481–487. https://doi.org/10.1039/c9nh00643e.
  19. Dong, J.; Zhu, C.; Zhang, F.; et al. “Attractive/adhesion force” dual-regulatory nanogels capable of CXCR4 antagonism and autophagy inhibition for the treatment of metastatic breast cancer. J. Control Release 2022, 341, 892–903. https://doi.org/10.1016/j.jconrel.2021.12.026.
  20. Deng, Y.; Song, P.; Chen, X.; et al. 3-Bromopyruvate-Conjugated Nanoplatform-Induced Pro-Death Autophagy for Enhanced Photodynamic Therapy against Hypoxic Tumor. ACS Nano 2020, 14, 9711–9727. https://doi.org/10.1021/acsnano.0c01350.
  21. Gao, G.; Sun, X.B.; Liu, X.Y.; et al. Intracellular Nanoparticle Formation and Hydroxychloroquine Release for Autophagy-Inhibited Mild-Temperature Photothermal Therapy for Tumors. Adv. Funct. Mater. 2021, 31, 2102832.
  22. Klionsky, D.J.; Abdel-Aziz, A.K.; Abdelfatah, S.; et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)(1). Autophagy 2021, 17, 1–382. https://doi.org/10.1080/15548627.2020.1797280.
  23. Klionsky, D.J.; Petroni, G.; Amaravadi, R.K.; et al. Autophagy in major human diseases. EMBO J. 2021, 40, e108863. https://doi.org/10.15252/embj.2021108863.
  24. Li, X.; He, S.; Ma, B. Autophagy and autophagy-related proteins in cancer. Mol. Cancer 2020, 19, 12. https://doi.org/10.1186/s12943-020-1138-4.
  25. Choi, I.; Wang, M.; Yoo, S.; et al. Autophagy enables microglia to engage amyloid plaques and prevents microglial senescence. Nat. Cell Biol. 2023, 25, 963–974. https://doi.org/10.1038/s41556-023-01158-0.
  26. Rubio-Tomas, T.; Sotiriou, A.; Tavernarakis, N. The interplay between selective types of (macro)autophagy: Mitophagy and xenophagy. Int. Rev. Cell Mol. Biol. 2023, 374, 129–157. https://doi.org/10.1016/bs.ircmb.2022.10.003.
  27. Feng, Y.; Chen, Y.; Wu, X.; et al. Interplay of energy metabolism and autophagy. Autophagy 2024, 20, 4–14. https://doi.org/10.1080/15548627.2023.2247300.
  28. Yamamoto, H.; Matsui, T. Molecular Mechanisms of Macroautophagy, Microautophagy, and Chaperone-Mediated Autophagy. J. Nippon. Med. Sch. 2024, 91, 2–9. https://doi.org/10.1272/jnms.JNMS.2024_91-102.
  29. Liao, Y.C.; Pang, S.; Li, W.P.; et al. COPII with ALG2 and ESCRTs control lysosome-dependent microautophagy of ER exit sites. Dev. Cell 2024, 59, 1410–1424.e1414. https://doi.org/10.1016/j.devcel.2024.03.027.
  30. Kuchitsu, Y.; Taguchi, T. Lysosomal microautophagy: an emerging dimension in mammalian autophagy. Trends Cell Biol. 2024, 34, 606–616. https://doi.org/10.1016/j.tcb.2023.11.005.
  31. Ryu, K.J.; Lee, K.W.; Park, S.H.; et al. Chaperone-mediated autophagy modulates Snail protein stability: implications for breast cancer metastasis. Mol. Cancer 2024, 23, 227. https://doi.org/10.1186/s12943-024-02138-0.
  32. Song, H.; Huang, W.; Jia, F.; et al. Targeted Degradation of Signal Transduction and Activator of Transcription 3 by Chaperone-Mediated Autophagy Targeting Chimeric Nanoplatform. ACS Nano 2024, 18, 1599–1610. https://doi.org/10.1021/acsnano.3c09536.
  33. Qin, Y.; Ashrafizadeh, M.; Mongiardini, V.; et al. Autophagy and cancer drug resistance in dialogue: Pre-clinical and clinical evidence. Cancer Lett. 2023, 570, 216307. https://doi.org/10.1016/j.canlet.2023.216307.
  34. Liu, Y.; Lu, S.; Wu, L.L.; et al The diversified role of mitochondria in ferroptosis in cancer. Cell Death Dis. 2023, 14, 519. https://doi.org/10.1038/s41419-023-06045-y.
  35. Deng, Y.; Jia, F.; Jiang, P.; et al. Biomimetic nanoparticle synchronizing pyroptosis induction and mitophagy inhibition for anti-tumor therapy. Biomaterials 2023, 301, 122293. https://doi.org/10.1016/j.biomaterials.2023.122293.
  36. Xia, Q.; Zhang, J. Interaction Between Autophagy and the Inflammasome in Human Tumors: Implications for the Treatment of Human Cancers. Cell Biochem. Funct. 2025, 43, e70035. https://doi.org/10.1002/cbf.70035.
  37. Das, N.; Mukherjee, S.; Das, A.; et al. Intra-tumor ROS amplification by melatonin interferes in the apoptosis-autophagy-inflammation-EMT collusion in the breast tumor microenvironment. Heliyon 2024, 10, e23870. https://doi.org/10.1016/j.heliyon.2023.e23870.
  38. Ji, J.; Cheng, X.; Du, R.; et al. Advances in research on autophagy mechanisms in resistance to endometrial cancer treatment. Front. Oncol. 2024, 14, 1364070. https://doi.org/10.3389/fonc.2024.1364070.
  39. Lee, M.J.; Park, J.S.; Jo, S.B.; et al. Enhancing Anti-Cancer Therapy with Selective Autophagy Inhibitors by Targeting Protective Autophagy. Biomol. Ther. 2023, 31, 1–15. https://doi.org/10.4062/biomolther.2022.153.
  40. Long, X.; Wang, H.; Yan, J.; et al. Tailor-Made Autophagy Cascade Amplification Polymeric Nanoparticles for Enhanced Tumor Immunotherapy. Small 2023, 19, e2207898. https://doi.org/10.1002/smll.202207898.
  41. Zhao, J.; Hou, X.; Zhao, C.; et al. Advances in Polymeric Nanomaterial-mediated Autophagy for Cancer Therapy. Chembiochem 2024, 25, e202400261. https://doi.org/10.1002/cbic.202400261.
  42. Wang, X.; Yang, L.; Zhang, H.; et al. Fluorescent magnetic PEI-PLGA nanoparticles loaded with paclitaxel for concurrent cell imaging, enhanced apoptosis and autophagy in human brain cancer. Colloids Surf. B Biointerfaces 2018, 172, 708–717. https://doi.org/10.1016/j.colsurfb.2018.09.033.
  43. Shen, J.M.; Yin, T.; Tian, X.Z.; et al. Surface charge-switchable polymeric magnetic nanoparticles for the controlled release of anticancer drug. ACS Appl. Mater. Interfaces 2013, 5, 7014–7024. https://doi.org/10.1021/am401277s.
  44. Wang, C.; Li, Z.; Xu, P.; et al. Combination of polythyleneimine regulating autophagy prodrug and Mdr1 siRNA for tumor multidrug resistance. J. Nanobiotechnol. 2022, 20, 476. https://doi.org/10.1186/s12951-022-01689-y.
  45. Jia, H.Z.; Zhang, W.; Zhu, J.Y.; et al. Hyperbranched-hyperbranched polymeric nanoassembly to mediate controllable co-delivery of siRNA and drug for synergistic tumor therapy. J. Control Release 2015, 216, 9–17. https://doi.org/10.1016/j.jconrel.2015.08.006.
  46. Golafzani, F.N.; Vaziri, A.Z.; Javanmardi, M.; et al. Delivery of miRNA-126 through folic acid-targeted biocompatible polymeric nanoparticles for effective lung cancer therapy. J. Bioact. Compat. Pol. 2022, 37, 168–188. https://doi.org/10.1177/08839115221095152.
  47. Cordani, M.; Somoza, A. Targeting autophagy using metallic nanoparticles: a promising strategy for cancer treatment. Cell Mol. Life Sci. 2019, 76, 1215–1242. https://doi.org/10.1007/s00018-018-2973-y.
  48. Piktel, E.; Oscilowska, I.; Suprewicz, L.; et al. ROS-Mediated Apoptosis and Autophagy in Ovarian Cancer Cells Treated with Peanut-Shaped Gold Nanoparticles. Int. J. Nanomed. 2021, 16, 1993–2011. https://doi.org/10.2147/IJN.S277014.
  49. Jawad, M.H.; Jabir, M.S.; Ozturk, K.; et al. Induction of apoptosis and autophagyregulation of AKT and JNK mitogen-activated protein kinase pathways in breast cancer cell lines exposed to gold nanoparticles loaded with TNF-α and combined with doxorubicin. Nanotechnol. Rev. 2023, 12, 20230148.
  50. Wang, R.; Xu, X.; Puja, A.M.; et al. Gold Nanoparticles Prepared with Phyllanthus emblica Fruit Extract and Bifidobacterium animalis subsp. lactis Can Induce Apoptosis via Mitochondrial Impairment with Inhibition of Autophagy in the Human Gastric Carcinoma Cell Line AGS. Nanomaterials 2021, 11, 1260. https://doi.org/10.3390/nano11051260.
  51. Zhang, S.; Xie, F.; Li, K.; et al. Gold nanoparticle-directed autophagy intervention for antitumor immunotherapy via inhibiting tumor-associated macrophage M2 polarization. Acta Pharm. Sin. B 2022, 12, 3124–3138. https://doi.org/10.1016/j.apsb.2022.02.008.
  52. Chen, Y.; Yang, T.; Chen, S.; et al. Silver nanoparticles regulate autophagy through lysosome injury and cell hypoxia in prostate cancer cells. J. Biochem. Mol. Toxicol. 2020, 34, e22474. https://doi.org/10.1002/jbt.22474.
  53. Struzynska, L. Dual Implications of Nanosilver-Induced Autophagy: Nanotoxicity and Anti-Cancer Effects. Int. J. Mol. Sci. 2023, 24. https://doi.org/10.3390/ijms242015386.
  54. Lin, J.; Huang, Z.; Wu, H.; et al. Inhibition of autophagy enhances the anticancer activity of silver nanoparticles. Autophagy 2014, 10, 2006–2020. https://doi.org/10.4161/auto.36293.
  55. Akter, M.; Atique Ullah, A.K.M.; Banik, S.; et al. Green Synthesized Silver Nanoparticles-Mediated Cytotoxic Effect in Colorectal Cancer Cells: NF-kappaB Signal Induced Apoptosis Through Autophagy. Biol. Trace Elem. Res. 2021, 199, 3272–3286. https://doi.org/10.1007/s12011-020-02463-7.
  56. Chen, Q.; Zhu, Y.F.; Wang, K.R.; et al. Clearing intratumoral bacteria to augment tumor-therapeutic response by engineering antimicrobial dendritic mesoporous silica nanomedicine. Nano Today 2023, 52, 101994.
  57. Li, Y.; Cho, M.H.; Lee, S.S.; et al. Hydroxychloroquine-loaded hollow mesoporous silica nanoparticles for enhanced autophagy inhibition and radiation therapy. J. Control Release 2020, 325, 100–110. https://doi.org/10.1016/j.jconrel.2020.06.025.
  58. Chen, T.; Cen, D.; Ren, Z.; et al. Bismuth embedded silica nanoparticles loaded with autophagy suppressant to promote photothermal therapy. Biomaterials 2019, 221, 119419. https://doi.org/10.1016/j.biomaterials.2019.119419.
  59. Zhang, P.; Tang, M.; Huang, Q.; et al. Combination of 3-methyladenine therapy and Asn-Gly-Arg (NGR)-modified mesoporous silica nanoparticles loaded with temozolomide for glioma therapy in vitro. Biochem. Biophys. Res. Commun. 2019, 509, 549–556. https://doi.org/10.1016/j.bbrc.2018.12.158.
  60. Khan, M.I.; Mohammad, A.; Patil, G.; et al. Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles. Biomaterials 2012, 33, 1477–1488. https://doi.org/10.1016/j.biomaterials.2011.10.080.
  61. Xie, Y.; Jiang, J.; Tang, Q.; et al. Iron Oxide Nanoparticles as Autophagy Intervention Agents Suppress Hepatoma Growth by Enhancing Tumoricidal Autophagy. Adv. Sci. 2020, 7, 1903323. https://doi.org/10.1002/advs.201903323.
  62. Wang, X.S.; Zeng, J.Y.; Li, M.J.; et al. Highly Stable Iron Carbonyl Complex Delivery Nanosystem for Improving Cancer Therapy. ACS Nano 2020, 14, 9848–9860. https://doi.org/10.1021/acsnano.0c02516.
  63. Lomphithak, T.; Helvacioglu, S.; Armenia, I.; et al. High-Dose Exposure to Polymer-Coated Iron Oxide Nanoparticles Elicits Autophagy-Dependent Ferroptosis in Susceptible Cancer Cells. Nanomaterials 2023, 13, 1719. https://doi.org/10.3390/nano13111719.
  64. Attri, K.; Chudasama, B.; Mahajan, R.L.; et al. Perturbation of hyperthermia resistance in gastric cancer by hyperstimulation of autophagy using artemisinin-protected iron-oxide nanoparticles. RSC Adv. 2024, 14, 34565–34577. https://doi.org/10.1039/d4ra05611f.
  65. Laha, D.; Pramanik, A.; Maity, J.; et al. Interplay between autophagy and apoptosis mediated by copper oxide nanoparticles in human breast cancer cells MCF7. Biochim. Biophys. Acta 2014, 1840, 1–9. https://doi.org/10.1016/j.bbagen.2013.08.011.
  66. Seo, Y.; Cho, Y.S.; Huh, Y.D.; et al. Copper Ion from Cu2O Crystal Induces AMPK-Mediated Autophagy via Superoxide in Endothelial Cells. Mol. Cells 2016, 39, 195–203. https://doi.org/10.14348/molcells.2016.2198.
  67. Li, S.R.; Tao, S.Y.; Li, Q.; et al. Harnessing nanomaterials for copper-induced cell death. Biomaterials 2025, 313, 122805. https://doi.org/10.1016/j.biomaterials.2024.122805.
  68. Wei, Z.; Si, W.; Huang, M.; et al. Autophagy Blockage Enhancing Photothermal and Chemodynamic Synergistic Therapy Based on HCQ/CuS Nanoplatform. Adv. Healthc. Mater. 2024, 13, e2402367. https://doi.org/10.1002/adhm.202402367.
  69. Zhang, L.; Chen, X.R.; Wu, J.Z.; et al. Palladium nanoparticles induce autophagy and autophagic flux blockade in Hela cells. RSC Adv. 2018, 8, 4130–4141. https://doi.org/10.1039/c7ra11400a.
  70. Aydinlik, S.; Erkisa, M.; Ari, F.; et al. Palladium (II) Complex Enhances ROS-Dependent Apoptotic Effects via Autophagy Inhibition and Disruption of Multiple Signaling Pathways in Colorectal Cancer Cells. Anticancer. Agents Med. Chem. 2021, 21, 1284–1291. https://doi.org/10.2174/1871520620666200929153804.
  71. Wang, Y.; Yin, S.; Zhang, L.; et al. A tumor-activatable particle with antimetastatic potential in breast cancer via inhibiting the autophagy-dependent disassembly of focal adhesion. Biomaterials 2018, 168, 1–9. https://doi.org/10.1016/j.biomaterials.2017.10.039.
  72. Wang, X.; Li, Y.; Cui, Y.; et al. Hierarchical assembly of dual-responsive biomineralized polydopamine-calcium phosphate nanocomposites for enhancing chemo-photothermal therapy by autophagy inhibition. Biomater. Sci. 2020, 8, 5172–5182. https://doi.org/10.1039/d0bm00142b.
  73. Yuan, G.; Xu, Y.; Bai, X.; et al. Autophagy-Targeted Calcium Phosphate Nanoparticles Enable Transarterial Chemoembolization for Enhanced Cancer Therapy. ACS Appl. Mater. Interfaces 2023, 15, 11431–11443. https://doi.org/10.1021/acsami.2c18267.
  74. Kretowski, R.; Cechowska-Pasko, M. The Reduced Graphene Oxide (rGO) Induces Apoptosis, Autophagy and Cell Cycle Arrest in Breast Cancer Cells. Int. J. Mol. Sci. 2022, 23, 9285. https://doi.org/10.3390/ijms23169285.
  75. Shen, J.; Dong, J.; Shao, F.; et al. Graphene oxide induces autophagy and apoptosis via the ROS-dependent AMPK/mTOR/ULK-1 pathway in colorectal cancer cells. Nanomedicine 2022, 17, 591–605. https://doi.org/10.2217/nnm-2022-0030.
  76. Taheriazam, A.; Abad, G.G.Y.; Hajimazdarany, S.; et al. Graphene oxide nanoarchitectures in cancer biology: Nano-modulators of autophagy and apoptosis. J. Control Release 2023, 354, 503–522. https://doi.org/10.1016/j.jconrel.2023.01.028.
  77. Liang, Q.; Yu, F.; Cai, H.; et al. Photo-activated autophagy-associated tumour cell death by lysosome impairment based on manganese-doped graphene quantum dots. J. Mater. Chem. B 2023, 11, 2466–2477. https://doi.org/10.1039/d2tb02761e.
  78. Akbari, A.; Nemati, M.; Lighvan, Z.M.; et al. Synthesis of metformin-derived fluorescent quantum dots: uptake, cytotoxicity, and inhibition in human breast cancer cells through autophagy pathway. J. Biol. Eng. 2024, 18, 38. https://doi.org/10.1186/s13036-024-00433-4.
  79. Shi, M.; Liu, Y.; Huang, J.; et al. Multifunctional theranostic nanoplatform loaded with autophagy inhibitor for enhanced photothermal cancer therapy under mild near-infrared irradiation. Biomater. Adv. 2022, 138, 212919. https://doi.org/10.1016/j.bioadv.2022.212919.
  80. Peng, J.; Zhou, J.; Liu, X.; et al. A biomimetic nanocarrier facilitates glucose consumption and reactive oxide species accumulation in enzyme therapy for colorectal cancer. J. Control Release 2024, 367, 76–92. https://doi.org/10.1016/j.jconrel.2024.01.041.
  81. Peng, J.; Zhou, J.; Sun, R.; et al. Dual-targeting of artesunate and chloroquine to tumor cells and tumor-associated macrophages by a biomimetic PLGA nanoparticle for colorectal cancer treatment. Int. J. Biol. Macromol. 2023, 244, 125163. https://doi.org/10.1016/j.ijbiomac.2023.125163.
  82. Hou, X.; Yang, C.; Zhang, L.; et al. Killing colon cancer cells through PCD pathways by a novel hyaluronic acid-modified shell-core nanoparticle loaded with RIP3 in combination with chloroquine. Biomaterials 2017, 124, 195–210. https://doi.org/10.1016/j.biomaterials.2016.12.032.
  83. Zhang, X.; Zeng, X.; Liang, X.; et al. The chemotherapeutic potential of PEG-b-PLGA copolymer micelles that combine chloroquine as autophagy inhibitor and docetaxel as an anti-cancer drug. Biomaterials 2014, 35, 9144–9154. https://doi.org/10.1016/j.biomaterials.2014.07.028.
  84. Castro, A.; Berois, N.; Malanga, A.; et al. Docetaxel in chitosan-based nanocapsules conjugated with an anti-Tn antigen mouse/human chimeric antibody as a promising targeting strategy of lung tumors. Int. J. Biol. Macromol. 2021, 182, 806–814. https://doi.org/10.1016/j.ijbiomac.2021.04.054.
  85. Bhagya, N.; Chandrashekar, K.R. Liposome encapsulated anticancer drugs on autophagy in cancer cells-Current and future perspective. Int. J. Pharm. 2023, 642, 123105.
  86. Li, J.; Cai, W.; Yu, J.; et al. Autophagy inhibition recovers deficient ICD-based cancer immunotherapy. Biomaterials 2022, 287, 121651. https://doi.org/10.1016/j.biomaterials.2022.121651.
  87. Sandha, K.K.; Kaur, S.; Sharma, K.; et al. Autophagy inhibition alleviates tumor desmoplasia and improves the efficacy of locally and systemically administered liposomal doxorubicin. J. Control Release 2025, 378, 1030–1044. https://doi.org/10.1016/j.jconrel.2024.12.078.
  88. Chang, C.M.; Lan, K.L.; Huang, W.S.; et al. Re-Liposome Can Induce Mitochondrial Autophagy and Reverse Drug Resistance for Ovarian Cancer: From Bench Evidence to Preliminary Clinical Proof-of-Concept. Int. J. Mol. Sci. 2017, 18, 903.
  89. Abo-Zaid, O.A.R.; Moawed, F.S.M.; Barakat, W.E.M.; et al. Antitumor activity of 5-fluorouracil polymeric nanogel synthesized by gamma radiation on a rat model of colon carcinoma: A proposed mechanism. Discov. Oncol. 2023, 14, 138. https://doi.org/10.1007/s12672-023-00733-z.
  90. Wang, Y.; Xu, Y.; Zhao, T.; et al. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection. Open Life Sci. 2024, 19, 20220952.
  91. Gao, J.; Zhai, Y.; Lu, W.; et al. ROS-sensitive PD-L1 siRNA cationic selenide nanogels for self-inhibition of autophagy and prevention of immune escape. Bioact. Mater. 2024, 41, 597–610. https://doi.org/10.1016/j.bioactmat.2024.08.013.
  92. Ding, L.; Wang, Q.; Shen, M.; et al. Thermoresponsive nanocomposite gel for local drug delivery to suppress the growth of glioma by inducing autophagy. Autophagy 2017, 13, 1176–1190. https://doi.org/10.1080/15548627.2017.1320634.
  93. Xu, L.; Mu, J.; Ma, Z.; et al. Nanozyme-Integrated Thermoresponsive In Situ Forming Hydrogel Enhances Mesenchymal Stem Cell Viability and Paracrine Effect for Efficient Spinal Cord Repair. ACS Appl. Mater. Interfaces 2023, 15, 37193–37204. https://doi.org/10.1021/acsami.3c06189.
  94. Hu, F.; Song, D.; Yan, Y.; et al. IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation. Nat. Commun. 2021, 12, 3651. https://doi.org/10.1038/s41467-021-23923-1.
  95. Wei, W.; Rosenkrans, Z.T.; Luo, Q.Y.; et al. Exploiting Nanomaterial-mediated Autophagy for Cancer Therapy. Small Methods 2019, 3, 1800365. https://doi.org/10.1002/smtd.201800365.
  96. Fitzwalter, B.E.; Towers, C.G.; Sullivan, K.D.; et al. Autophagy Inhibition Mediates Apoptosis Sensitization in Cancer Therapy by Relieving FOXO3a Turnover. Dev. Cell 2018, 44, 555–565.e3. https://doi.org/10.1016/j.devcel.2018.02.014.
  97. Lu, H.Y.; Chang, Y.J.; Fan, N.C.; et al. Synergism through combination of chemotherapy and oxidative stress-induced autophagy in A549 lung cancer cells using redox-responsive nanohybrids: a new strategy for cancer therapy. Biomaterials 2015, 42, 30–41. https://doi.org/10.1016/j.biomaterials.2014.11.029.
  98. Chen, X.; Mendes, B.B.; Zhuang, Y.H.; et al. A Fluorinated BODIPY-Based Zirconium Metal-Organic Framework forEnhanced Photodynamic Therapy. J. Am. Chem. Soc. 2024, 146, 1644–1656. https://doi.org/10.1021/jacs.3c12416.
  99. Chang, M.Q.; Dai, X.Y.; Dong, C.H.; et al. Two-dimensional persistent luminescence “optical battery” for autophagy inhibition-augmented photodynamic tumor nanotherapy. Nano Today 2022, 42, 101362.
  100. Sun, Q.Q.; Chen, W.L.; Wang, M.; et al. A “Chase and Block” Strategy for Enhanced Cancer Therapy with Hypoxia-Promoted Photodynamic Therapy and Autophagy Inhibition Based on Upconversion Nanocomposites. Adv. Healthc. Mater. 2023, 12, 2301087. https://doi.org/10.1002/adhm.202301087.
  101. Deng, X.; Guan, W.; Qing, X.; et al. Ultrafast Low-Temperature Photothermal Therapy Activates Autophagy and Recovers Immunity for Efficient Antitumor Treatment. ACS Appl. Mater. Interfaces 2020, 12, 4265–4275. https://doi.org/10.1021/acsami.9b19148.
  102. Mu, J.X.; Meng, Z.X.; Liu, X.R.; et al. Implantable Nanofiber Membranes with Synergistic Photothermal and Autophagy Inhibition Effects for Enhanced Tumor Therapy Efficacy. Adv. Fiber Mater. 2023, 5, 1810–1825. https://doi.org/10.1007/s42765-023-00311-6.
  103. Peng, S.S.; Wang, L.Z.; Liu, L.; et al. Inhibition of Pro-Survival Autophagy Induced by Rare-Earth Nanocomposites for Promoting Photothermal Therapy of Visualized Tumors. Adv. Healthc. Mater. 2023, 12, 2202117. https://doi.org/10.1002/adhm.202202117.
  104. Yang, F.; Dong, J.; Li, Z.; et al. Metal-Organic Frameworks (MOF)-Assisted Sonodynamic Therapy in Anticancer Applications. ACS Nano 2023, 17, 4102–4133. https://doi.org/10.1021/acsnano.2c10251.
  105. Liang, S.; Yao, J.; Liu, D.; et al. Harnessing Nanomaterials for Cancer Sonodynamic Immunotherapy. Adv. Mater. 2023, 35, e2211130. https://doi.org/10.1002/adma.202211130.
  106. Wang, M.F.; Guo, J.; Yuan, S.J.; et al. Targeted sonodynamic therapy induces tumor cell quasi-immunogenic ferroptosis and macrophage immunostimulatory autophagy in glioblastoma. Biomaterials 2025, 315, 122913. https://doi.org/10.1016/j.biomaterials.2024.122913.
  107. Zhang, X.; Lao, M.; Yang, H.; et al. Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance. Autophagy 2024, 20, 1314–1334. https://doi.org/10.1080/15548627.2023.2300913.
  108. Chen, M.; Yang, D.; Sun, Y.; et al. In Situ Self-Assembly Nanomicelle Microneedles for Enhanced Photoimmunotherapy via Autophagy Regulation Strategy. ACS Nano 2021, 15, 3387–3401. https://doi.org/10.1021/acsnano.0c10396.
  109. Cifuentes-Rius, A.; Desai, A.; Yuen, D.; et al. Inducing immune tolerance with dendritic cell-targeting nanomedicines. Nat. Nanotechnol. 2021, 16, 37–46. https://doi.org/10.1038/s41565-020-00810-2.
  110. Shi, G.N.; Zhang, C.N.; Xu, R.; et al. Enhanced antitumor immunity by targeting dendritic cells with tumor cell lysate-loaded chitosan nanoparticles vaccine. Biomaterials 2017, 113, 191–202. https://doi.org/10.1016/j.biomaterials.2016.10.047.
  111. Fu, Y.; He, Y.; Wei, X.; et al. Sonocatalysis Regulates Tumor Autophagy for Enhanced Immunotherapy. ACS Nano 2024, 18, 28793–28809. https://doi.org/10.1021/acsnano.4c08468.
  112. Yang, B.; Ding, L.; Chen, Y.; et al. Augmenting Tumor-Starvation Therapy by Cancer Cell Autophagy Inhibition. Adv. Sci. 2020, 7, 1902847. https://doi.org/10.1002/advs.201902847.
  113. Zhang, R.; Zhang, C.; Chen, C.; et al. Autophagy-Activated Self-reporting Photosensitizer Promoting Cell Mortality in Cancer Starvation Therapy. Adv. Sci. 2023, 10, e2301295. https://doi.org/10.1002/advs.202301295.
  114. Chen, J.Q.; Zhu, Z.Y.; Pan, Q.Y.; et al. Targeted Therapy of Oral Squamous Cell Carcinoma with Cancer Cell Membrane Coated Co-Fc Nanoparticles Via Autophagy Inhibition. Adv. Funct. Mater. 2023, 33. https://doi.org/10.1002/adfm.202300235.
  115. Wan, S.S.; Zhang, L.; Zhang, X.Z. An ATP-Regulated Ion Transport Nanosystem for Homeostatic Perturbation Therapy and Sensitizing Photodynamic Therapy by Autophagy Inhibition of Tumors. ACS Cent. Sci. 2019, 5, 327–340. https://doi.org/10.1021/acscentsci.8b00822.