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Abstract
Traditional cancer therapies are often limited by nonspecific distribution, leading to systemic toxicity and poor therapeutic outcomes. Targeted drug delivery systems aim to overcome these limitations by directing therapeutic agents specifically to tumor tissues, minimizing off-target effects. Recent advances have introduced sophisticated platforms, including nanoparticles, liposomes, dendrimers, micelles, and antibody-drug conjugates (ADCs). This review explores the design principles of these delivery systems, their mechanisms of targeting (passive via the enhanced permeability and retention effect and active via ligand-receptor interactions), and their clinical applications. Challenges such as drug resistance, immunogenicity, and tumor heterogeneity are also discussed. Future directions include stimuli-responsive systems, personalized nanomedicine, and combination therapies integrating immunotherapy and targeted delivery.
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References
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- Morales-Cruz M, Delgado Y, Castillo B, Figueroa CM, Molina AM, Torres A, Milián M, Griebenow K. Smart targeting to improve cancer therapeutics. Drug design, development and therapy. 2019 Oct 30:3753-72. Doi:https://doi.org/10.2147/DDDT.S219489
- Li J, Wang Q, Xia G, Adilijiang N, Li Y, Hou Z, Fan Z, Li J. Recent advances in targeted drug delivery strategy for enhancing oncotherapy. Pharmaceutics. 2023 Aug 29;15(9):2233. Doi:https://doi.org/10.3390/pharmaceutics15092233
- Kreuzinger C, Geroldinger A, Smeets D, Braicu EI, Sehouli J, Koller J, Wolf A, Darb-Esfahani S, Joehrens K, Vergote I, Vanderstichele A. A complex network of tumor microenvironment in human high-grade serous ovarian cancer. Clinical Cancer Research. 2017 Dec 15;23(24):7621-32. Doi:https://doi.org/10.1158/1078-0432.CCR-17-1159.
- Yu H, Ning N, Meng X, Chittasupho C, Jiang L, Zhao Y. Sequential drug delivery in targeted cancer therapy. Pharmaceutics. 2022 Mar 5;14(3):573. Doi:https://doi.org/10.3390/pharmaceutics14030573
- Sanchez-Moreno P, Ortega-Vinuesa JL, Peula-Garcia JM, Marchal JA, Boulaiz H. Smart drug-delivery systems for cancer nanotherapy. Current drug targets. 2018 Mar 1;19(4):339-59. Doi:https://doi.org/10.2174/1389450117666160527142544
- Park JW. Liposome-based drug delivery in breast cancer treatment. Breast Cancer Research. 2002 Jun;4:1-5. Doi:https://doi.org/10.1186/bcr432
- Allahou LW, Madani SY, Seifalian A. Investigating the application of liposomes as drug delivery systems for the diagnosis and treatment of cancer. International journal of biomaterials. 2021;2021(1):3041969. Doi:https://doi.org/10.1155/2021/3041969
- Kim EG, Kim KM. Strategies and advancement in antibody-drug conjugate optimization for targeted cancer therapeutics. Biomolecules & therapeutics. 2015 Nov 1;23(6):493. Doi:https://doi.org/10.4062/biomolther.2015.116
- Peters C, Brown S. Antibody–drug conjugates as novel anti-cancer chemotherapeutics. Bioscience reports. 2015 Jul 14;35(4):e00225. Doi:https://doi.org/10.1042/BSR20150089
- Hanafy NA, El-Kemary M, Leporatti S. Micelles structure development as a strategy to improve smart cancer therapy. Cancers. 2018 Jul 20;10(7):238. Doi:https://doi.org/10.3390/cancers10070238
- Zhang Y, Sun C. Current status, challenges and prospects of antifouling materials for oncology applications. Frontiers in Oncology. 2024 May 8;14:1391293. Doi:https://doi.org/10.3389/fonc.2024.1391293
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- Yoo J, Park C, Yi G, Lee D, Koo H. Active targeting strategies using biological ligands for nanoparticle drug delivery systems. Cancers. 2019 May 8;11(5):640. Doi:https://10.3390/cancers11050640.
- Lim EK, Jang E, Lee K, Haam S, Huh YM. Delivery of cancer therapeutics using nanotechnology. Pharmaceutics. 2013 May 15;5(2):294-317. Doi:https://10.3390/pharmaceutics5020294
- Rosenblum D, Joshi N, Tao W, Karp JM, Peer D. Progress and challenges towards targeted delivery of cancer therapeutics. Nature communications. 2018 Apr 12;9(1):1410. Doi:https://doi.org/10.1038/s41467-018-03705-y
- Zhang Y, Zheng X, Huang Y, Li S, Li X, Zhu L. EDB-FN-targeted probes for near infrared fluorescent imaging and positron emission tomography imaging of breast cancer in mice. Scientific Reports. 2024 Sep 27;14(1):22056. Doi:https://doi.org/10.1038/s41598-024-73362-3
- Gupta C, Jaipuria A, Gupta N. Inhalable formulations to treat non-small cell lung cancer (NSCLC): Recent therapies and developments. Pharmaceutics. 2022 Dec 31;15(1):139. Doi:https:// doi.org/10.3390/pharmaceutics15010139
- Durfee PN. Synthesis, characterization, and application of monosized mesoporous silica nanoparticle-supported lipid bilayers for targeted therapeutic delivery to individual cells (Doctoral dissertation, The University of New Mexico). Doi:https://doi.org/10.1021/acsnano.6b02819. Epub 2016 Jul 25
- Balzer AH, Whitehurst CB. An analysis of the biotin–(strept) avidin system in immunoassays: Interference and mitigation strategies. Current Issues in Molecular Biology. 2023 Oct 31;45(11):8733-54. Doi:https://doi.org/10.3390/cimb45110549.
- Parveen S, Gupta P, Kumar S, Banerjee M. Lipid polymer hybrid nanoparticles as potent vehicles for drug delivery in cancer therapeutics. Medicine in Drug Discovery. 2023 Dec 1;20:100165. Doi:https://doi.org/10.1016/j.medidd.2023.100165
- Korsmeyer R. Critical questions in development of targeted nanoparticle therapeutics. Regenerative Biomaterials. 2016 Jun 1;3(2):143-7. Doi:https://doi.org/10.1093/rb/rbw011.
- Lang X, Wang X, Han M, Guo Y. Nanoparticle-mediated synergistic chemoimmunotherapy for cancer treatment. International Journal of Nanomedicine. 2024 Dec 31:4533-68. Doi:https://doi.org/10.2147/IJN.S455213
- Huang R, Zhu J, Fan R, Tang Y, Hu L, Lee H, Chen S. Extracellular vesicle-based drug delivery systems in cancer. Extracellular Vesicle. 2024 Dec 1;4:100053. Doi:https://doi.org/10.1016/j.vesic.2024.100053
References
Brown JS, Amend SR, Austin RH, Gatenby RA, Hammarlund EU, Pienta KJ. Updating the definition of cancer. Molecular Cancer Research. 2023 Nov 1;21(11):1142-7. Doi: https://doi.org/10.1158/1541-7786.MCR-23-0411.
Anand U, Dey A, Chandel AK, Sanyal R, Mishra A, Pandey DK, De Falco V, Upadhyay A, Kandimalla R, Chaudhary A, Dhanjal JK. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes & diseases. 2023 Jul 1;10(4):1367-401. 10.1016/j.gendis.2022.02.007
Morales-Cruz M, Delgado Y, Castillo B, Figueroa CM, Molina AM, Torres A, Milián M, Griebenow K. Smart targeting to improve cancer therapeutics. Drug design, development and therapy. 2019 Oct 30:3753-72. Doi:https://doi.org/10.2147/DDDT.S219489
Li J, Wang Q, Xia G, Adilijiang N, Li Y, Hou Z, Fan Z, Li J. Recent advances in targeted drug delivery strategy for enhancing oncotherapy. Pharmaceutics. 2023 Aug 29;15(9):2233. Doi:https://doi.org/10.3390/pharmaceutics15092233
Kreuzinger C, Geroldinger A, Smeets D, Braicu EI, Sehouli J, Koller J, Wolf A, Darb-Esfahani S, Joehrens K, Vergote I, Vanderstichele A. A complex network of tumor microenvironment in human high-grade serous ovarian cancer. Clinical Cancer Research. 2017 Dec 15;23(24):7621-32. Doi:https://doi.org/10.1158/1078-0432.CCR-17-1159.
Yu H, Ning N, Meng X, Chittasupho C, Jiang L, Zhao Y. Sequential drug delivery in targeted cancer therapy. Pharmaceutics. 2022 Mar 5;14(3):573. Doi:https://doi.org/10.3390/pharmaceutics14030573
Sanchez-Moreno P, Ortega-Vinuesa JL, Peula-Garcia JM, Marchal JA, Boulaiz H. Smart drug-delivery systems for cancer nanotherapy. Current drug targets. 2018 Mar 1;19(4):339-59. Doi:https://doi.org/10.2174/1389450117666160527142544
Park JW. Liposome-based drug delivery in breast cancer treatment. Breast Cancer Research. 2002 Jun;4:1-5. Doi:https://doi.org/10.1186/bcr432
Allahou LW, Madani SY, Seifalian A. Investigating the application of liposomes as drug delivery systems for the diagnosis and treatment of cancer. International journal of biomaterials. 2021;2021(1):3041969. Doi:https://doi.org/10.1155/2021/3041969
Kim EG, Kim KM. Strategies and advancement in antibody-drug conjugate optimization for targeted cancer therapeutics. Biomolecules & therapeutics. 2015 Nov 1;23(6):493. Doi:https://doi.org/10.4062/biomolther.2015.116
Peters C, Brown S. Antibody–drug conjugates as novel anti-cancer chemotherapeutics. Bioscience reports. 2015 Jul 14;35(4):e00225. Doi:https://doi.org/10.1042/BSR20150089
Hanafy NA, El-Kemary M, Leporatti S. Micelles structure development as a strategy to improve smart cancer therapy. Cancers. 2018 Jul 20;10(7):238. Doi:https://doi.org/10.3390/cancers10070238
Zhang Y, Sun C. Current status, challenges and prospects of antifouling materials for oncology applications. Frontiers in Oncology. 2024 May 8;14:1391293. Doi:https://doi.org/10.3389/fonc.2024.1391293
Yoon DJ, Liu CT, Quinlan DS, Nafisi PM, Kamei DT. Intracellular trafficking considerations in the development of natural ligand-drug molecular conjugates for cancer. Annals of biomedical engineering. 2011 Apr;39:1235-51. Doi:https://10.1007/s10439-011-0280-y
Yoo J, Park C, Yi G, Lee D, Koo H. Active targeting strategies using biological ligands for nanoparticle drug delivery systems. Cancers. 2019 May 8;11(5):640. Doi:https://10.3390/cancers11050640.
Lim EK, Jang E, Lee K, Haam S, Huh YM. Delivery of cancer therapeutics using nanotechnology. Pharmaceutics. 2013 May 15;5(2):294-317. Doi:https://10.3390/pharmaceutics5020294
Rosenblum D, Joshi N, Tao W, Karp JM, Peer D. Progress and challenges towards targeted delivery of cancer therapeutics. Nature communications. 2018 Apr 12;9(1):1410. Doi:https://doi.org/10.1038/s41467-018-03705-y
Zhang Y, Zheng X, Huang Y, Li S, Li X, Zhu L. EDB-FN-targeted probes for near infrared fluorescent imaging and positron emission tomography imaging of breast cancer in mice. Scientific Reports. 2024 Sep 27;14(1):22056. Doi:https://doi.org/10.1038/s41598-024-73362-3
Gupta C, Jaipuria A, Gupta N. Inhalable formulations to treat non-small cell lung cancer (NSCLC): Recent therapies and developments. Pharmaceutics. 2022 Dec 31;15(1):139. Doi:https:// doi.org/10.3390/pharmaceutics15010139
Durfee PN. Synthesis, characterization, and application of monosized mesoporous silica nanoparticle-supported lipid bilayers for targeted therapeutic delivery to individual cells (Doctoral dissertation, The University of New Mexico). Doi:https://doi.org/10.1021/acsnano.6b02819. Epub 2016 Jul 25
Balzer AH, Whitehurst CB. An analysis of the biotin–(strept) avidin system in immunoassays: Interference and mitigation strategies. Current Issues in Molecular Biology. 2023 Oct 31;45(11):8733-54. Doi:https://doi.org/10.3390/cimb45110549.
Parveen S, Gupta P, Kumar S, Banerjee M. Lipid polymer hybrid nanoparticles as potent vehicles for drug delivery in cancer therapeutics. Medicine in Drug Discovery. 2023 Dec 1;20:100165. Doi:https://doi.org/10.1016/j.medidd.2023.100165
Korsmeyer R. Critical questions in development of targeted nanoparticle therapeutics. Regenerative Biomaterials. 2016 Jun 1;3(2):143-7. Doi:https://doi.org/10.1093/rb/rbw011.
Lang X, Wang X, Han M, Guo Y. Nanoparticle-mediated synergistic chemoimmunotherapy for cancer treatment. International Journal of Nanomedicine. 2024 Dec 31:4533-68. Doi:https://doi.org/10.2147/IJN.S455213
Huang R, Zhu J, Fan R, Tang Y, Hu L, Lee H, Chen S. Extracellular vesicle-based drug delivery systems in cancer. Extracellular Vesicle. 2024 Dec 1;4:100053. Doi:https://doi.org/10.1016/j.vesic.2024.100053