Downloads

Yi, S., Ren, X., Liu, J., & Yu, L. Drug Delivery Systems for Enhancing Cancer Chemotherapy. Medical Materials Research. 2025. doi: Retrieved from https://w3.sciltp.com/journals/mmr/article/view/995
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

Drug Delivery Systems for Enhancing Cancer Chemotherapy

Shuanglong Yi 1,†, Xueli Ren 1,†, Jie Liu 1,* and Luodan Yu 1,2,*

1 Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China

2 Department of Radiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine,
Shanghai 200030, China

* Correspondence: 728003093@shsmu.edu.cn (J.L.); yuluodan@shu.edu.cn (L.Y.)

† These authors contributed equally to this work.

Received: 24 February 2025; Revised: 12 March 2025; Accepted: 24 March 2025; Published: 2 April 2025

Abstract: Cancer chemotherapy remains one of the most effective treatment strategies, but its clinical success is often limited by challenges such as poor drug bioavailability, non-specific toxicity, and drug resistance. Drug delivery systems (DDSs) have emerged as a promising solution to overcome these barriers, offering enhanced efficacy and reduced side effects. For instance, liposomal doxorubicin (Doxil®) has significantly improved treatment outcomes in triple-negative breast cancer (TNBC) by reducing cardiotoxicity, while albumin-bound paclitaxel (Abraxane®) enhances drug solubility and tumor targeting in glioblastoma. This review focuses on the classification of DDSs, drug loading methods, and surface functionalization strategies, which enable targeted drug delivery, controlled release, and improved cellular uptake. Additionally, we explore the integration of stimuli-responsive systems that can release chemotherapeutic agents in situ in response to endogenous or exogenous stimuli. The potential of multifunctional DDSs to combine chemotherapy with radiotherapy, phototherapy, ultrasound therapy, immunotherapy, and imaging is also discussed. Despite promising results, the clinical translation of these systems faces challenges, including manufacturing scalability, regulatory approval, and safety concerns. Future directions for the development of more efficient and personalized DDSs for cancer treatment are also proposed.

Keywords:

nanoparticles drug delivery systems cancer therapy targeted therapy nanotechnology

References

  1. 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 A Cancer J. Clin. 2024, 74, 229–263. https://doi.org/10.3322/caac.21834.
  2. Li, L.; Shan, T.; Zhang, D.; et al. Nowcasting and forecasting global aging and cancer burden: Analysis of data from the GLOBOCAN and Global Burden of Disease Study. J. Natl. Cancer Cent. 2024, 4, 223–232.
  3. Collaborators, G.A. Global, regional, and national burden of diseases and injuries for adults 70 years and older: Systematic analysis for the Global Burden of Disease 2019 Study. Br. Med. J. 2022, 376, e068208.
  4. Amjad, M.T.; Chidharla, A.; Kasi, A. Cancer Chemotherapy; StatPearls Publishing: Treasure Island, FL, USA, 2023.
  5. Zeien, J.; Qiu, W.; Triay, M.; et al. Clinical implications of chemotherapeutic agent organ toxicity on perioperative care. Biomed. Pharmacother. 2022, 146, 112503.
  6. Ahmad, S.S.; Reinius, M.A.; Hatcher, H.M.; et al. Anticancer chemotherapy in teenagers and young adults: Managing long term side effects. Br. Med. J. 2016, 354, i4567.
  7. Duan, C.; Yu, M.; Xu, J.; et al. Overcoming Cancer Multi-drug Resistance (MDR): Reasons, mechanisms, nanotherapeutic solutions, and challenges. Biomed. Pharmacother. 2023, 162, 114643.
  8. Wang, M.; Chen, W.; Chen, J.; et al. Abnormal saccharides affecting cancer multi-drug resistance (MDR) and the reversal strategies. Eur. J. Med. Chem. 2021, 220, 113487.
  9. Bukowski, K.; Kciuk, M.; Kontek, R. Mechanisms of multidrug resistance in cancer chemotherapy. Int. J. Mol. Sci. 2020, 21, 3233.
  10. De Visser, K.E.; Joyce, J.A. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell 2023, 41, 374–403.
  11. Tilsed, C.M.; Fisher, S.A.; Nowak, A.K.; et al. Cancer chemotherapy: Insights into cellular and tumor microenvironmental mechanisms of action. Front. Oncol. 2022, 12, 960317.
  12. Kemp, J.A.; Kwon, Y.J. Cancer nanotechnology: Current status and perspectives. Nano Converg. 2021, 8, 34.
  13. Klochkov, S.G.; Neganova, M.E.; Nikolenko, V.N.; et al. Implications of nanotechnology for the treatment of cancer: Recent advances. Semin. Cancer Biol. 2021, 69, 190–199.
  14. Yadav, P.; Ambudkar, S.V.; Rajendra Prasad, N. Emerging nanotechnology-based therapeutics to combat multidrug-resistant cancer. J. Nanobiotechnol. 2022, 20, 423.
  15. Yang, Z.; Cai, Y.; Yang, X.; et al. Novel benzo five-membered heterocycle derivatives as P-glycoprotein inhibitors: Design, synthesis, molecular docking, and anti-multidrug resistance activity. J. Med. Chem. 2023, 66, 5550–5566.
  16. Montesinos, R.N.; Béduneau, A.; Pellequer, Y.; et al. Delivery of P-glycoprotein substrates using chemosensitizers and nanotechnology for selective and efficient therapeutic outcomes. J. Control. Release 2012, 161, 50–61.
  17. Almawash, S.; Chaturvedi, S.; Misra, C.; et al. Vitamin E TPGS-PLGA-based nanoparticles for methotrexate delivery: Promising outcomes from preclinical studies. J. Drug Deliv. Sci. Technol. 2022, 72, 103276.
  18. Peihsuan, H.; Weiyuan, H.; Huanchih, W.; et al. Dual-responsive polypeptide nanoparticles attenuate tumor-associated stromal desmoplasia and anticancer through programmable dissociation. Biomaterials 2022, 284, 121469.
  19. Lingmei, L.; Yipin, X.; Yurong, Q.; et al. Tumor microenvironment-responsive drug self-delivery systems to treat cancer and overcome MDR. Rare Met. 2025, 44, 1–33.
  20. Zhang, W.; Li, S.; Liu, X.; et al. Oxygen-generating MnO2 nanodots-anchored versatile nanoplatform for combined chemo-photodynamic therapy in hypoxic cancer. Adv. Funct. Mater. 2018, 28, 1706375.
  21. Wu, B.; Shi, X.; Jiang, M.; et al. Cross-talk between cancer stem cells and immune cells: Potential therapeutic targets in the tumor immune microenvironment. Mol. Cancer 2023, 22, 38.
  22. Navarro-Marchal, S.A.; Grinan-Lison, C.; Entrena, J.-M.; et al. Anti-CD44-conjugated olive oil liquid nanocapsules for targeting pancreatic cancer stem cells. Biomacromolecules 2021, 22, 1374–1388.
  23. Li, C.; Liang, Y.; Cao, J.; et al. The delivery of a Wnt pathway inhibitor toward CSCs requires stable liposome encapsulation and delayed drug release in tumor tissues. Mol. Ther. 2019, 27, 1558–1567.
  24. Kirtane, A.R.; Kalscheuer, S.M.; Panyam, J. Exploiting nanotechnology to overcome tumor drug resistance: Challenges and opportunities. Adv. Drug Deliv. Rev. 2013, 65, 1731–1747.
  25. Li, J.; Liu, C.; Hu, Y.; et al. pH-responsive perylenediimide nanoparticles for cancer trimodality imaging and photothermal therapy. Theranostics 2020, 10, 166.
  26. Zeng, Z.; Zhang, C.; Li, J.; et al. Activatable polymer nanoenzymes for photodynamic immunometabolic cancer therapy. Adv. Mater. 2021, 33, 2007247.
  27. Hong, L.; Li, W.; Li, Y.; et al. Nanoparticle-based drug delivery systems targeting cancer cell surfaces. RSC Adv. 2023, 13, 21365–21382.
  28. Antimisiaris, S.; Marazioti, A.; Kannavou, M.; et al. Overcoming barriers by local drug delivery with liposomes. Adv. Drug Deliv. Rev. 2021, 174, 53–86.
  29. Rarokar, N.R.; Saoji, S.D.; Raut, N.A.; et al. Nanostructured cubosomes in a thermoresponsive depot system: An alternative approach for the controlled delivery of docetaxel. AAPS Pharmscitech 2016, 17, 436–445.
  30. Bhattacharya, S.; Saoji, S.D. Development, optimization, and characterization of polymeric micelles to improve dasatinib oral bioavailability: Hep G2 cell cytotoxicity and in vivo pharmacokinetics for targeted liver cancer therapy. Heliyon 2024, 10, e39632.
  31. Patil, J.; Bhattacharya, S.; Saoji, S.D.; et al. Cabozantinib-phospholipid complex for enhanced solubility, bioavailability, and reduced toxicity in liver cancer. Ther. Deliv. 2025, 16, 25–41.
  32. Kalluri, R.; LeBleu, V.S. The biology, function, and biomedical applications of exosomes. Science 2020, 367, eaau6977.
  33. Chao, Y.; Chen, Q.; Liu, Z. Smart injectable hydrogels for cancer immunotherapy. Adv. Funct. Mater. 2020, 30, 1902785.
  34. Singh, N.; Son, S.; An, J.; et al. Nanoscale porous organic polymers for drug delivery and advanced cancer theranostics. Chem. Soc. Rev. 2021, 50, 12883–12896.
  35. Bracho-Sanchez, E.; Xia, C.Q.; Clare-Salzler, M.J.; et al. Micro and nano material carriers for immunomodulation. Am. J. Transplant. 2016, 16, 3362–3370.
  36. Setyawati, M.I.; Wang, Q.; Ni, N.; et al. Engineering tumoral vascular leakiness with gold nanoparticles. Nat. Commun. 2023, 14, 4269.
  37. Li, X.; Li, Y.; Yu, C.; et al. ROS-responsive janus Au/mesoporous silica core/shell nanoparticles for drug delivery and long-term CT imaging tracking of MSCs in pulmonary fibrosis treatment. ACS Nano 2023, 17, 6387–6399.
  38. Li, H.; Yang, S.; Hui, D.; et al. Progress in magnetic Fe3O4 nanomaterials in magnetic resonance imaging. Nanotechnol. Rev. 2020, 9, 1265–1283.
  39. Fan, X.; Jiao, G.; Gao, L.; et al. The preparation and drug delivery of a graphene–carbon nanotube–Fe3O4 nanoparticle hybrid. J. Mater. Chem. B 2013, 1, 2658–2664.
  40. Chen, G.; Qian, Y.; Zhang, H.; et al. Advances in cancer theranostics using organic-inorganic hybrid nanotechnology. Appl. Mater. Today 2021, 23, 101003.
  41. Ding, S.; He, L.; Bian, X.; et al. Metal-organic frameworks-based nanozymes for combined cancer therapy. Nano Today 2020, 35, 100920.
  42. Cho, N.-H.; Cheong, T.-C.; Min, J.H.; et al. A multifunctional core–shell nanoparticle for dendritic cell-based cancer immunotherapy. Nat. Nanotechnol. 2011, 6, 675–682.
  43. Pan, Y.; Zhao, H.; Huang, W.; et al. Metal-Protein Hybrid Materials: Unlocking New Frontiers in Biomedical Applications. Adv. Healthc. Mater. 2025, 14, 2404405.
  44. Zhao, Q.; Sun, X.; Wu, B.; et al. Construction of homologous cancer cell membrane camouflage in a nano-drug delivery system for the treatment of lymphoma. J. Nanobiotechnol. 2021, 19, 1–19.
  45. Nazari, M.; Minai-Tehrani, A.; Mousavi, S.; et al. Development of recombinant biomimetic nano-carrier for targeted gene transfer to HER3 positive breast cancer. Int. J. Biol. Macromol. 2021, 189, 948–955.
  46. Jain, A.; Reddy, V.A.; Muntimadugu, E.; et al. Nanotechnology in vaccine delivery. Curr. Trends Pharm. Sci. 2014, 1, 17–27.
  47. Barrera, Y.B.; Hause, G.; Menzel, M.; et al. Engineering osteogenic microenvironments by combination of multilayers from collagen type I and chondroitin sulfate with novel cationic liposomes. Mater. Today Bio 2020, 7, 100071.
  48. Gao, C.; Huang, Q.; Liu, C.; et al. Treatment of atherosclerosis by macrophage-biomimetic nanoparticles via targeted pharmacotherapy and sequestration of proinflammatory cytokines. Nat. Commun. 2020, 11, 2622. https://doi.org/10.1038/s41467-020-16439-7.
  49. Yang, L.; Zhang, Y.; Zhang, Y.; et al. Live macrophage-delivered doxorubicin-loaded liposomes effectively treat triple-negative breast cancer. ACS Nano 2022, 16, 9799–9809.
  50. He, Q.; Gao, Y.; Zhang, L.; et al. A pH-responsive mesoporous silica nanoparticles-based multi-drug delivery system for overcoming multi-drug resistance. Biomaterials 2011, 32, 7711–7720.
  51. Cui, Y.; Xu, Q.; Chow, P.K.-H.; et al. Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment. Biomaterials 2013, 34, 8511–8520.
  52. Martínez-Carmona, M.; Lozano, D.; Colilla, M.; et al. Lectin-conjugated pH-responsive mesoporous silica nanoparticles for targeted bone cancer treatment. Acta Biomater. 2018, 65, 393–404.
  53. Zhang, D.; Liu, L.; Wang, J.; et al. Drug-loaded PEG-PLGA nanoparticles for cancer treatment. Front. Pharmacol. 2022, 13, 990505.
  54. Arrieta, V.A.; Gould, A.; Kim, K.-S.; et al. Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas. Nat. Commun. 2024, 15, 4698.
  55. Tapeinos, C.; Battaglini, M.; Ciofani, G. Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases. J. Control. Release 2017, 264, 306–332.
  56. Sung, Y.K.; Kim, S.W. Recent advances in polymeric drug delivery systems. Biomater. Res. 2020, 24, 12.
  57. He, Z.; Chen, W.; Hu, K.; et al. Resolvin D1 delivery to lesional macrophages using antioxidative black phosphorus nanosheets for atherosclerosis treatment. Nat. Nanotechnol. 2024, 19, 1386–1398. https://doi.org/10.1038/s41565-024-01687-1.
  58. Zhang, Y.; Yan, C.; Dong, Y.; et al. ANGPTL3 accelerates atherosclerotic progression via direct regulation of M1 macrophage activation in plaque. J. Adv. Res. 2024, 70, 125–138. https://doi.org/10.1016/j.jare.2024.05.011.
  59. Rahman, M.M.; Wang, J.; Wang, G.; et al. Chimeric nanobody-decorated liposomes by self-assembly. Nat. Nanotechnol. 2024, 19, 818–824.
  60. Wei, D.; Huang, Y.; Wang, B.; et al. Photo-Reduction with NIR Light of Nucleus-Targeting PtIV Nanoparticles for Combined Tumor-Targeted Chemotherapy and Photodynamic Immunotherapy. Angew. Chem. Int. Ed. 2022, 61, e202201486.
  61. Marques, A.C.; Costa, P.; Velho, S.; Amaral, M.H. Functionalizing nanoparticles with cancer-targeting antibodies: A comparison of strategies. J. Control. Release 2020, 320, 180–200.
  62. Ma, K.; Li, W.; Zhu, G.; et al. Functionalized PDA/DEX-PEI@ HA nanoparticles combined with sleeping-beauty transposons for multistage targeted delivery of CRISPR/Cas9 gene. Biomed. Pharmacother. 2021, 142, 112061.
  63. Li, C.-X.; Qi, Y.-D.; Feng, J.; et al. Cell-Based Bio-Hybrid Delivery System for Disease Treatments. Adv. Nanobiomed Res. 2021, 1, 2000052.
  64. Kwon, S.; Shin, S.; Do, M.; et al. Engineering approaches for effective therapeutic applications based on extracellular vesicles. J. Control. Release 2021, 330, 15–30.
  65. Deng, X.; Li, K.; Cai, X.; et al. A hollow-structured CuS@ Cu2S@ Au nanohybrid: Synergistically enhanced photothermal efficiency and photoswitchable targeting effect for cancer theranostics. Adv. Mater. 2017, 29, 1701266.
  66. Zhang, Y.; Wang, Y.; Zhu, A.; et al. Dual-Targeting Biomimetic Semiconducting Polymer Nanocomposites for Amplified Theranostics of Bone Metastasis. Angew. Chem. 2024, 136, e202310252.
  67. Patil, Y.B.; Toti, U.S.; Khdair, A.; et al. Single-step surface functionalization of polymeric nanoparticles for targeted drug delivery. Biomaterials 2009, 30, 859–866.
  68. Tian, Y.; Gao, Z.; Wang, N.; et al. Engineering poly (ethylene glycol) nanoparticles for accelerated blood clearance inhibition and targeted drug delivery. J. Am. Chem. Soc. 2022, 144, 18419–18428.
  69. Shubhra, Q.T.; Guo, K.; Liu, Y.; et al. Dual targeting smart drug delivery system for multimodal synergistic combination cancer therapy with reduced cardiotoxicity. Acta Biomater. 2021, 131, 493–507.
  70. Lin, Y.; Zhou, H.; Chen, N.; et al. Unveiling the improved targeting migration of mesenchymal stem cells with CXC chemokine receptor 3-modification using intravital NIR-II photoacoustic imaging. J. Nanobiotechnol. 2022, 20, 307.
  71. Xiao, W.; Wang, Y.; Zhang, H.; et al. The protein corona hampers the transcytosis of transferrin-modified nanoparticles through blood–brain barrier and attenuates their targeting ability to brain tumor. Biomaterials 2021, 274, 120888.
  72. Zhou, J.; Ji, Q.; Li, Q. Resistance to anti-EGFR therapies in metastatic colorectal cancer: Underlying mechanisms and reversal strategies. J. Exp. Clin. Cancer Res. 2021, 40, 328.
  73. Raikwar, S.; Yadav, V.; Jain, S.; et al. Antibody-conjugated pH-sensitive liposomes for HER-2 positive breast cancer: Development, characterization, in vitro and in vivo assessment. J. Liposome Res. 2024, 34, 239–263.
  74. Luo, Z.; Yan, Z.; Jin, K.; et al. Precise glioblastoma targeting by AS1411 aptamer-functionalized poly (l-γ-glutamylglutamine)–paclitaxel nanoconjugates. J. Colloid Interface Sci. 2017, 490, 783–796.
  75. Kesharwani, P.; Halwai, K.; Jha, S.K.; et al. Folate-engineered chitosan nanoparticles: Next-generation anticancer nanocarriers. Mol. Cancer 2024, 23, 244.
  76. Chen, Y.; Chen, X.; Zhang, Y.; et al. Macrophage-specific in vivo RNA editing promotes phagocytosis and antitumor immunity in mice. Sci. Transl. Med. 2025, 17, eadl5800. https://doi.org/10.1126/scitranslmed.adl5800.
  77. Wang, Y.; Li, H.; Niu, G.; et al. Boosting sono-immunotherapy of prostate carcinoma through amplifying domino-effect of mitochondrial oxidative stress using biodegradable cascade-targeting nanocomposites. ACS Nano 2024, 18, 5828–5846.
  78. Xiao, Z.; Li, T.; Zheng, X.; et al. Nanodrug enhances post-ablation immunotherapy of hepatocellular carcinoma via promoting dendritic cell maturation and antigen presentation. Bioact. Mater. 2023, 21, 57–68.
  79. Oh, J.Y.; Jana, B.; Seong, J.; et al. Unveiling the Power of Cloaking Metal–Organic Framework Platforms via Supramolecular Antibody Conjugation. ACS Nano 2024, 18, 15790–15801.
  80. Yoo, J.-W.; Irvine, D.J.; Discher, D.E.; et al. Bio-inspired, bioengineered and biomimetic drug delivery carriers. Nat. Rev. Drug Discov. 2011, 10, 521–535.
  81. Han, X.; Gong, C.; Yang, Q.; et al. Biomimetic nano-drug delivery system: An emerging platform for promoting tumor treatment. Int. J. Nanomed. 2024, 19, 571–608.
  82. Tang, L.; He, S.; Yin, Y.; et al. Combination of nanomaterials in cell-based drug delivery systems for cancer treatment. Pharmaceutics 2021, 13, 1888.
  83. Guo, Q.; Qian, Z.-M. Macrophage based drug delivery: Key challenges and strategies. Bioact. Mater. 2024, 38, 55–72.
  84. Wang, X.; Lu, J.; Mao, Y.; et al. A mutually beneficial macrophages-mediated delivery system realizing photo/immune therapy. J. Control. Release 2022, 347, 14–26.
  85. Ding, J.; Lu, Y.; Zhao, X.; et al. Activating Iterative Revolutions of the Cancer-Immunity Cycle in Hypoxic Tumors with a Smart Nano-Regulator. Adv. Mater. 2024, 36, 2400196.
  86. Lin, H.; Chen, Y.; Shi, J. Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy. Chem. Soc. Rev. 2018, 47, 1938–1958.
  87. Cook, A.B.; Decuzzi, P. Harnessing endogenous stimuli for responsive materials in theranostics. ACS Nano 2021, 15, 2068–2098.
  88. De La Rica, R.; Aili, D.; Stevens, M.M. Enzyme-responsive nanoparticles for drug release and diagnostics. Adv. Drug Deliv. Rev. 2012, 64, 967–978.
  89. Wang, H.; Chen, Y.; Wang, H.; et al. DNAzyme-loaded metal–organic frameworks (MOFs) for self-sufficient gene therapy. Angew. Chem. 2019, 131, 7458–7462.
  90. Wang, L.; Wang, T.; Zhang, Y.; et al. Biomimetic nanosystems harnessing NIR-II photothermal effect and hypoxia-responsive prodrug for self-amplifying and synergistic tumor treatment. Nano Today 2024, 57, 102395.
  91. Mura, S.; Nicolas, J.; Couvreur, P. Stimuli-responsive nanocarriers for drug delivery. Nat. Mater. 2013, 12, 991–1003.
  92. Zhang, Q.; Kuang, G.; Li, W.; et al. Stimuli-responsive gene delivery nanocarriers for cancer therapy. Nano-Micro Lett. 2023, 15, 44.
  93. Lei, Q.; Zhou, W.; Gao, S.; et al. Ultrasound-responsive metal–organic framework-based nanosystem for sonodynamic therapy/amplified ferroptosis/Ido-blockade osteosarcoma immunotherapy. Chem. Eng. J. 2024, 490, 151614.
  94. Fu, Q.; Zhang, S.; Shen, S.; et al. Radiotherapy-triggered reduction of platinum-based chemotherapeutic prodrugs in tumours. Nat. Biomed. Eng. 2024, 8, 1425–1435.
  95. Zhang, Y.; Yu, J.; Bomba, H.N.; et al. Mechanical force-triggered drug delivery. Chem. Rev. 2016, 116, 12536–12563.
  96. 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.
  97. Liu, C.; Wang, D.; Zhang, S.; et al. Biodegradable biomimic copper/manganese silicate nanospheres for chemodynamic/photodynamic synergistic therapy with simultaneous glutathione depletion and hypoxia relief. ACS Nano 2019, 13, 4267–4277.
  98. Li, J.; Liu, F.; Shao, Q.; et al. Enzyme-responsive cell-penetrating peptide conjugated mesoporous silica quantum dot nanocarriers for controlled release of nucleus-targeted drug molecules and real-time intracellular fluorescence imaging of tumor cells. Adv. Healthc. Mater. 2014, 3, 1230–1239.
  99. Thambi, T.; Deepagan, V.; Yoon, H.Y.; et al. Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery. Biomaterials 2014, 35, 1735–1743.
  100. Wang, Y.; Kohane, D.S. External triggering and triggered targeting strategies for drug delivery. Nat. Rev. Mater. 2017, 2, 17020.
  101. Chen, F.; Ruan, F.; Xie, X.; et al. Gold Nanocluster: A Photoelectric Converter for X-Ray-Activated Chemotherapy. Adv. Mater. 2024, 36, 2402966.
  102. Karimi, M.; Ghasemi, A.; Zangabad, P.S.; et al. Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems. Chem. Soc. Rev. 2016, 45, 1457–1501.
  103. Shirin, V.A.; Sankar, R.; Johnson, A.P.; et al. Advanced drug delivery applications of layered double hydroxide. J. Control. Release 2021, 330, 398–426.
  104. Izci, M.; Maksoudian, C.; Manshian, B.B.; et al. The use of alternative strategies for enhanced nanoparticle delivery to solid tumors. Chem. Rev. 2021, 121, 1746–1803.
  105. Almoshari, Y. Development, therapeutic evaluation and theranostic applications of cubosomes on cancers: An updated review. Pharmaceutics 2022, 14, 600.
  106. Mitchell, M.J.; Billingsley, M.M.; Haley, R.M.; et al. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 2021, 20, 101–124.
  107. Meng, L.; Gan, S.; Zhou, Y.; et al. Oxygen-rich chemotherapy via modified Abraxane to inhibit the growth and metastasis of triple-negative breast cancer. Biomater. Sci. 2019, 7, 168–177.
  108. Hoy, S.M. Albumin-bound paclitaxel: A review of its use for the first-line combination treatment of metastatic pancreatic cancer. Drugs 2014, 74, 1757–1768.
  109. Setyawati, M.; Tay, C.; Chia, S.; et al. Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin. Nat. Commun. 2013, 4, 1673.
  110. Peng, F.; Setyawati, M.I.; Tee, J.K.; et al. Nanoparticles promote in vivo breast cancer cell intravasation and extravasation by inducing endothelial leakiness. Nat. Nanotechnol. 2019, 14, 279–286.
  111. Xu, Z.; Zhen, W.; McCleary, C.; et al. Nanoscale Metal-Organic Framework with an X-ray Triggerable Prodrug for Synergistic Radiotherapy and Chemotherapy. J Am Chem Soc. 2023, 145, 18698–18704.
  112. Chen, Z.; Li, S.; Li, F.; et al. DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild-Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression. Adv. Sci. 2023, 10, e2206707. https://doi.org/10.1002/advs.202206707.
  113. Chen, H.; Zhang, S.; Fang, Q.; et al. Biomimetic Nanosonosensitizers Combined with Noninvasive Ultrasound Actuation to Reverse Drug Resistance and Sonodynamic-Enhanced Chemotherapy against Orthotopic Glioblastoma. ACS Nano 2023, 17, 421–436. https://doi.org/10.1021/acsnano.2c08861.
  114. Liao, Z.; Niu, Y.; Wang, Z.; et al. A “Nonsolvent Quenching” Strategy for 3D Printing of Polysaccharide Scaffolds with Immunoregulatory Accuracy. Adv. Sci. 2022, 9, e2203236. https://doi.org/10.1002/advs.202203236.
  115. Ma, Y.; Morozova, S.M.; Kumacheva, E. From Nature-Sourced Polysaccharide Particles to Advanced Functional Materials. Adv. Mater. 2024, 36, e2312707. https://doi.org/10.1002/adma.202312707.
  116. Wu, Q.; Hu, Y.; Yu, B.; et al. Polysaccharide-based tumor microenvironment-responsive drug delivery systems for cancer therapy. J. Control. Release 2023, 362, 19–43. https://doi.org/10.1016/j.jconrel.2023.08.019.
  117. Huang, C.; Xie, T.; Liu, Y.; et al. A Sodium Alginate-Based Multifunctional Nanoplatform for Synergistic Chemo-Immunotherapy of Hepatocellular Carcinoma. Adv. Mater. 2023, 35, e2301352. https://doi.org/10.1002/adma.202301352.
  118. Jin, Y.; Li, D.; Zheng, X.; et al. A Novel Activatable Nanoradiosensitizer for Second Near-Infrared Fluorescence Imaging-Guided Safe-Dose Synergetic Chemo-Radiotherapy of Rheumatoid Arthritis. Adv. Sci. 2024, 11, e2308905. https://doi.org/10.1002/advs.202308905.
  119. Zeng, F.; Fan, Z.; Li, S.; et al. Tumor Microenvironment Activated Photoacoustic-Fluorescence Bimodal Nanoprobe for Precise Chemo-immunotherapy and Immune Response Tracing of Glioblastoma. ACS Nano 2023, 17, 19753–19766. https://doi.org/10.1021/acsnano.3c03378.
  120. Li, G.; Shi, S.; Tan, J.; et al. Highly Efficient Synergistic Chemotherapy and Magnetic Resonance Imaging for Targeted Ovarian Cancer Therapy Using Hyaluronic Acid-Coated Coordination Polymer Nanoparticles. Adv. Sci. 2024, 11, e2309464. https://doi.org/10.1002/advs.202309464.
  121. Theivendren, P.; Kunjiappan, S.; Pavadai, P.; et al. Revolutionizing Cancer Immunotherapy: Emerging Nanotechnology-Driven Drug Delivery Systems for Enhanced Therapeutic Efficacy. ACS Meas. Sci. Au 2024, 5, 31–35.
  122. Ding, Y.; Su, S.; Zhang, R.; et al. Precision combination therapy for triple negative breast cancer via biomimetic polydopamine polymer core-shell nanostructures. Biomaterials 2017, 113, 243–252.
  123. Zhang, Q.; Shan, W.; Ai, C.; et al. Construction of multifunctional Fe3O4-MTX@ HBc nanoparticles for MR imaging and photothermal therapy/chemotherapy. Nanotheranostics 2018, 2, 87.
  124. Landesman-Milo, D.; Peer, D. Altering the immune response with lipid-based nanoparticles. J. Control. Release 2012, 161, 600–608.
  125. Ho, K.-W.; Liu, Y.-L.; Liao, T.-Y.; et al. Strategies for Non-Covalent Attachment of Antibodies to PEGylated Nanoparticles for Targeted Drug Delivery. Int. J. Nanomed. 2024, 19, 10045–10064.
  126. Saaiq, M. Clinical and Demographic Profile of Volkmann’s Ischemic Contractures Presenting at National Institute of Rehabilitation Medicine, Islamabad, Pakistan. World J. Plast. Surg. 2020, 9, 166.
  127. Mohn, F.; Scheffler, K.; Ackers, J.; et al. Characterization of the clinically approved MRI tracer resotran for magnetic particle imaging in a comparison study. Phys. Med. Biol. 2024, 69, 135014.
  128. Cheng, L.; Wang, C.; Feng, L.; et al. Functional nanomaterials for phototherapies of cancer. Chem. Rev. 2014, 114, 10869–10939.
  129. Shi, J.; Kantoff, P.W.; Wooster, R.; et al. Cancer nanomedicine: Progress, challenges and opportunities. Nat. Rev. Cancer 2017, 17, 20–37.
  130. Rosenblum, D.; Joshi, N.; Tao, W.; et al. Progress and challenges towards targeted delivery of cancer therapeutics. Nat. Commun. 2018, 9, 1410.
  131. Anselmo, A.C.; Mitragotri, S. Nanoparticles in the clinic: An update. Bioeng. Transl. Med. 2019, 4, e10143.
  132. Li, L.; Yang, W.-W.; Xu, D.-G. Stimuli-responsive nanoscale drug delivery systems for cancer therapy. J. Drug Target. 2019, 27, 423–433.
  133. Ge, K.; Ren, Y.; Hong, Z.; et al. Microchip Based Isolation and Drug Delivery of Patient-Derived Extracellular Vesicles Against Their Homologous Tumor. Adv. Healthc. Mater. 2024, 13, 2401990.
  134. Garbuzenko, O.B.; Sapiezynski, J.; Girda, E.; et al. Personalized Versus Precision Nanomedicine for Treatment of Ovarian Cancer. Small 2024, 20, 2307462. https://doi.org/10.1002/smll.202307462.
  135. Aundhia, C.; Parmar, G.; Talele, C.; et al. Impact of artificial intelligence on drug development and delivery. Curr. Top. Med. Chem. 2024, 24, e15680266324522. https://doi.org/10.2174/0115680266324522240725053634.
  136. Elbadawi, M.; McCoubrey, L.E.; Gavins, F.K.; et al. Harnessing artificial intelligence for the next generation of 3D printed medicines. Adv. Drug Deliv. Rev. 2021, 175, 113805.
  137. Ahmed, M. Modulation of the Tumor Microenvironment to Overcome Glioblastoma Treatment Resistance. Ph.D. Thesis, Université Paris-Saclay, Orsay, France, 2021.
  138. Blanco, E.; Shen, H.; Ferrari, M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 2015, 33, 941–951.
  139. Karlsson, J.; Vaughan, H.J.; Green, J.J. Biodegradable polymeric nanoparticles for therapeutic cancer treatments. Annu. Rev. Chem. Biomol. Eng. 2018, 9, 105–127.