PLGA Nanoparticle in Tumor Immunotherapy: Advances in Research and Application
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PLGA Nanoparticle in Tumor Immunotherapy: Advances in Research and Application

Ziquan Gan 1*
1 Central South University
*Corresponding author: 845080710@qq.com
Published on 26 November 2025
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TNS Vol.152
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-80590-565-3
ISBN (Online): 978-1-80590-566-0
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Abstract

Immunotherapy holds significant promise in the cancer treatment, but its clinical application is hindered by challenges such as systemic toxicity and limited targeting efficiency. In recent years, biodegradable PLGA nanoparticle have emerged as a promising tool to address the safety and efficacy challenges of immunotherapy, owing to their high biocompatibility and capabilities for drug delivery. This article provides a comprehensive review of the research and application of PLGA nanoparticle in tumor immunotherapy, emphasizing their mechanisms and advantages as multifunctional drug carriers for co-delivering antigens and adjuvants, remodeling the tumor microenvironment, and enhancing immune responses. This review offers new insights for the development of low-toxicity, high-efficiency personalized immunotherapy strategies and holds significant potential for future clinical translation through advanced material design and technological integration.

Keywords:

PLGA nanoparticle, Tumor, Immunotherapy, Drug delivery

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Gan,Z. (2025). PLGA Nanoparticle in Tumor Immunotherapy: Advances in Research and Application. Theoretical and Natural Science,152,24-33.

References

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[2]. Wu, Y., Xu, J., Liu, Y., Zeng, Y. & Wu, G. A Review on Anti-Tumor Mechanisms of Coumarins. Front Oncol 10, 592853 (2020).

[3]. Zhang, G. et al. Emodin influences pyroptosis-related Caspase 1-GSDMD axis alleviated cerebral ischemia-reperfusion injury in rats. Sci Rep 15, 19397 (2025).

[4]. Rusch, T., Bayry, J., Werner, J., Shevchenko, I. & Bazhin, A. V. Immunotherapy as an Option for Cancer Treatment. Arch Immunol Ther Exp (Warsz) 66, 89–96 (2018).

[5]. Cheung, P. F., Lutz, M. & Siveke, J. T. Immunotherapy and Combination Strategies in Pancreatic Cancer: Current Status and Emerging Trends. Oncol Res Treat 41, 286–290 (2018).

[6]. Kim, S. M., Patel, M. & Patel, R. PLGA Core-Shell Nano/Microparticle Delivery System for Biomedical Application. Polymers (Basel) 13, 3471 (2021).

[7]. Sheffey, V. V., Siew, E. B., Tanner, E. E. L. & Eniola-Adefeso, O. PLGA’s Plight and the Role of Stealth Surface Modification Strategies in Its Use for Intravenous Particulate Drug Delivery. Adv Healthc Mater 11, e2101536 (2022).

[8]. Gao, L., Li, J. & Song, T. Poly lactic-co-glycolic acid-based nanoparticles as delivery systems for enhanced cancer immunotherapy. Front. Chem. 10, (2022).

[9]. Horvath, D. & Basler, M. PLGA Particles in Immunotherapy. Pharmaceutics 15, 615 (2023).

[10]. Application of PLGA in Tumor Immunotherapy. https: //www.mdpi.com/2073-4360/16/9/1253.

[11]. Xuan, F. et al. Biomimetic Co-delivery of Lenvatinib and FePt Nanoparticles for Enhanced Ferroptosis/Apoptosis Treatment of Hepatocellular Carcinoma. Adv Healthc Mater 14, e2401747 (2025).

[12]. Truchan, K., Zagrajczuk, B., Cholewa-Kowalska, K. & Osyczka, A. M. Rapid osteoinduction of human adipose-derived stem cells grown on bioactive surfaces and stimulated by chemically modified media flow. J Biol Eng 19, 23 (2025).

[13]. Bridgeman, C. J., Shah, S. A., Oakes, R. S. & Jewell, C. M. Dissecting regulatory T cell expansion using polymer microparticles presenting defined ratios of self-antigen and regulatory cues. Front Bioeng Biotechnol 11, 1184938 (2023).

[14]. Antioxidants: Classification, Natural Sources, Activity/Capacity Measurements, and Usefulness for the Synthesis of Nanoparticles. https: //www.mdpi.com/1996-1944/14/15/4135.

[15]. Nano-Radiopharmaceuticals in Colon Cancer: Current Applications, Challenges, and Future Directions. https: //www.mdpi.com/1424-8247/18/2/257.

[16]. Current Research Trends and Hotspots in Radiotherapy Combined with Nanomaterials for Cancer Treatment: A Bibliometric and Visualization Analysis. https: //www.mdpi.com/2079-4991/15/15/1205.

[17]. Pakulska, M. M. et al. Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles. Sci Adv 2, e1600519 (2016).

[18]. Leelakanok, N., Geary, S. & Salem, A. Fabrication and Use of Poly(d, l-lactide-co-glycolide)-Based Formulations Designed for Modified Release of 5-Fluorouracil. J Pharm Sci 107, 513–528 (2018).

[19]. Comparative Nanofabrication of PLGA-Chitosan-PEG Systems Employing Microfluidics and Emulsification Solvent Evaporation Techniques. https: //www.mdpi.com/2073-4360/12/9/1882.

[20]. Full article: Polymer-based prolonged-release nanoformulation of duloxetine: fabrication, characterization and neuropharmacological assessments. https: //www.tandfonline.com/doi/10.1080/03639045.2020.1851240?url_ver=Z39.88-2003& rfr_id=ori: rid: crossref.org& rfr_dat=cr_pub%20%200pubmed.

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[22]. Nath, S. D., Son, S., Sadiasa, A., Min, Y. K. & Lee, B. T. Preparation and characterization of PLGA microspheres by the electrospraying method for delivering simvastatin for bone regeneration. International Journal of Pharmaceutics 443, 87–94 (2013).

[23]. Yue, J., Liu, Z., Wang, L., Wang, M. & Pan, G. Recent advances in bioactive hydrogel microspheres: Material engineering strategies and biomedical prospects. Materials Today Bio 31, 101614 (2025).

[24]. Research Progress of Protein-Based Bioactive Substance Nanoparticles. https: //www.mdpi.com/2304-8158/12/16/2999.

[25]. Liu, Q. et al. Continuous preparation of long-acting hydromorphone PLGA microspheres using an automatic and scalable microfluidic process system. International Journal of Pharmaceutics 674, 125459 (2025).

[26]. Microfluidic preparation of monodisperse PLGA-PEG/PLGA microspheres with controllable morphology for drug release - Lab on a Chip (RSC Publishing). https: //pubs.rsc.org/en/content/articlelanding/2024/lc/d4lc00486h.

[27]. Xia, Y. et al. Liquid jet breakup: A new method for the preparation of poly lactic-co-glycolic acid microspheres. European Journal of Pharmaceutics and Biopharmaceutics 137, 140–147 (2019).

[28]. Müller-Ruch, U., Skorska, A., Lemcke, H., Steinhoff, G. & David, R. GLP: A requirement in cell therapies - perspectives for the cardiovascular field. Advanced Drug Delivery Reviews 165–166, 96–104 (2020).

[29]. Zhang, G. et al. Recent advances of nanoparticles on bone tissue engineering and bone cells. Nanoscale Adv 6, 1957–1973 (2024).

[30]. Guo, X. et al. Progress on liposome delivery systems in the treatment of bladder cancer. RSC Adv 15, 14315–14336 (2025).

[31]. Junyaprasert, V. B. & Thummarati, P. Innovative Design of Targeted Nanoparticles: Polymer-Drug Conjugates for Enhanced Cancer Therapy. Pharmaceutics 15, 2216 (2023).

[32]. Danhier, F. To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine? Journal of Controlled Release 244, 108–121 (2016).

[33]. Golombek, S. K. et al. Tumor targeting via EPR: Strategies to enhance patient responses. Advanced Drug Delivery Reviews 130, 17–38 (2018).

[34]. Progress and challenges towards targeted delivery of cancer therapeutics - PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC5897557/.

[35]. van der Meel, R. et al. Smart cancer nanomedicine. Nat. Nanotechnol. 14, 1007–1017 (2019).

[36]. Engineered Nanoparticles for Cancer Vaccination and Immunotherapy | Accounts of Chemical Research. https: //pubs.acs.org/doi/10.1021/acs.accounts.0c00456.

[37]. Li, Q. et al. Symphony of nanomaterials and immunotherapy based on the cancer–immunity cycle. Acta Pharmaceutica Sinica B 12, 107–134 (2022).

[38]. Nanoparticle-enhanced chemo-immunotherapy to trigger robust antitumor immunity | Science Advances. https: //www.science.org/doi/10.1126/sciadv.abc3646?url_ver=Z39.88-2003& rfr_id=ori: rid: crossref.org& rfr_dat=cr_pub%20%200pubmed.

[39]. Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis. https: //www.mdpi.com/1422-0067/24/14/11367.

[40]. Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies. https: //www.mdpi.com/2072-6694/13/11/2607.

[41]. Nagaraj, H. et al. Breaking the cellular delivery bottleneck: recent developments in direct cytosolic delivery of biologics. RSC Pharm 2, 850–864.

[42]. Cheng, Z. et al. Lipid-based nanosystems: the next generation of cancer immune therapy. J Hematol Oncol 17, 53 (2024).

[43]. Anbazhagan, M. K. & Mahalingam, S. Advancements in nanofibers and nanocomposites: Cutting-edge innovations for tissue engineering and drug delivery—A review. Sci Prog 108, 00368504241300842 (2025).

[44]. da Silva, A. F., Gonçalves, L. M. D., Fernandes, A. & Almeida, A. J. Optimization and evaluation of a chitosan-coated PLGA nanocarrier for mucosal delivery of Porphyromonas gingivalis antigens. European Journal of Pharmaceutical Sciences 202, 106896 (2024).

[45]. Yang, D. et al. Quaternized chitosan-coated PLGA nanoparticles co-deliver resveratrol and all-trans retinoic acid to enhance humoral immunity, cellular immunity and gastrointestinal mucosal immunity. Colloids and Surfaces B: Biointerfaces 256, 114994 (2025).

[46]. Yu, J. et al. Immunocytes in the tumor microenvironment: recent updates and interconnections. Front Immunol 16, 1517959 (2025).

[47]. Liu, X. et al. The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy. Front Oncol 11, 720842 (2021).

[48]. Lee, C. K. et al. Anti-PD-L1 F(ab) Conjugated PEG-PLGA Nanoparticle Enhances Immune Checkpoint Therapy. Nanotheranostics 6, 243–255 (2022).

[49]. Zhang, N. et al. Photothermal therapy mediated by phase-transformation nanoparticles facilitates delivery of anti-PD1 antibody and synergizes with antitumor immunotherapy for melanoma. Journal of Controlled Release 306, 15–28 (2019).

[50]. Immune checkpoint silencing using RNAi-incorporated nanoparticles enhances antitumor immunity and therapeutic efficacy compared with antibody-based approaches | Journal for ImmunoTherapy of Cancer. https: //jitc.bmj.com/content/10/2/e003928.

[51]. Han, Y., Tian, X., Zhai, J. & Zhang, Z. Clinical application of immunogenic cell death inducers in cancer immunotherapy: turning cold tumors hot. Front Cell Dev Biol 12, 1363121 (2024).

[52]. Cheng, C., Wang, Q. & Zhang, S. Synergy of oncolytic adenovirus and immune checkpoint inhibitors: transforming cancer immunotherapy paradigms. Front Immunol 16, 1610858 (2025).

[53]. Development of Toll-like Receptor Agonist-Loaded Nanoparticles as Precision Immunotherapy for Reprogramming Tumor-Associated Macrophages | ACS Applied Materials & Interfaces. https: //pubs.acs.org/doi/10.1021/acsami.1c01453.

[54]. Zhao, X. et al. Inducing enhanced immunogenic cell death with nanocarrier-based drug delivery systems for pancreatic cancer therapy. Biomaterials 102, 187–197 (2016).

[55]. Chen, P.-M. et al. Modulation of tumor microenvironment using a TLR-7/8 agonist-loaded nanoparticle system that exerts low-temperature hyperthermia and immunotherapy for in situ cancer vaccination. Biomaterials 230, 119629 (2020).

[56]. Wang, B. et al. Advances in immunotherapy and targeted therapy for advanced clear-cell renal cell carcinoma: current strategies and future directions. Front Immunol 16, 1582887 (2025).

[57]. Li, X., Song, R., Zhu, J., He, J. & Liu, X. A multidimensional analysis and future perspectives of cellular cancer vaccines. Biochem Biophys Res Commun 780, 152380 (2025).

[58]. Dölen, Y. et al. PLGA Nanoparticles Co-encapsulating NY-ESO-1 Peptides and IMM60 Induce Robust CD8 and CD4 T Cell and B Cell Responses. Front Immunol 12, 641703 (2021).

[59]. Creemers, J. H. A. et al. Assessing the safety, tolerability and efficacy of PLGA-based immunomodulatory nanoparticles in patients with advanced NY-ESO-1-positive cancers: a first-in-human phase I open-label dose-escalation study protocol. BMJ Open 11, e050725 (2021).

[60]. Chen, Q. et al. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat Commun 7, 13193 (2016).

[61]. Hybrid nanovaccine for the co-delivery of the mRNA antigen and adjuvant - Nanoscale (RSC Publishing). https: //pubs.rsc.org/en/content/articlelanding/2019/nr/c9nr05475h.

[62]. Koerner, J., Horvath, D. & Groettrup, M. Harnessing Dendritic Cells for Poly (D, L-lactide-co-glycolide) Microspheres (PLGA MS)—Mediated Anti-tumor Therapy. Front Immunol 10, 707 (2019).

[63]. Koerner, J. et al. PLGA-particle vaccine carrying TLR3/RIG-I ligand Riboxxim synergizes with immune checkpoint blockade for effective anti-cancer immunotherapy. Nat Commun 12, 2935 (2021).

[64]. Suxin, L., Bennett, Z. T., Sumer, B. D. & Gao, J. Nano-Immune-Engineering Approaches to Advance Cancer Immunotherapy: Lessons from Ultra-pH-Sensitive Nanoparticles. Acc Chem Res 53, 2546–2557 (2020).

References

[1]. Wan, W. et al. The optimization and application of photodynamic diagnosis and autofluorescence imaging in tumor diagnosis and guided surgery: current status and future prospects. Front Oncol 14, 1503404 (2024).

[2]. Wu, Y., Xu, J., Liu, Y., Zeng, Y. & Wu, G. A Review on Anti-Tumor Mechanisms of Coumarins. Front Oncol 10, 592853 (2020).

[3]. Zhang, G. et al. Emodin influences pyroptosis-related Caspase 1-GSDMD axis alleviated cerebral ischemia-reperfusion injury in rats. Sci Rep 15, 19397 (2025).

[4]. Rusch, T., Bayry, J., Werner, J., Shevchenko, I. & Bazhin, A. V. Immunotherapy as an Option for Cancer Treatment. Arch Immunol Ther Exp (Warsz) 66, 89–96 (2018).

[5]. Cheung, P. F., Lutz, M. & Siveke, J. T. Immunotherapy and Combination Strategies in Pancreatic Cancer: Current Status and Emerging Trends. Oncol Res Treat 41, 286–290 (2018).

[6]. Kim, S. M., Patel, M. & Patel, R. PLGA Core-Shell Nano/Microparticle Delivery System for Biomedical Application. Polymers (Basel) 13, 3471 (2021).

[7]. Sheffey, V. V., Siew, E. B., Tanner, E. E. L. & Eniola-Adefeso, O. PLGA’s Plight and the Role of Stealth Surface Modification Strategies in Its Use for Intravenous Particulate Drug Delivery. Adv Healthc Mater 11, e2101536 (2022).

[8]. Gao, L., Li, J. & Song, T. Poly lactic-co-glycolic acid-based nanoparticles as delivery systems for enhanced cancer immunotherapy. Front. Chem. 10, (2022).

[9]. Horvath, D. & Basler, M. PLGA Particles in Immunotherapy. Pharmaceutics 15, 615 (2023).

[10]. Application of PLGA in Tumor Immunotherapy. https: //www.mdpi.com/2073-4360/16/9/1253.

[11]. Xuan, F. et al. Biomimetic Co-delivery of Lenvatinib and FePt Nanoparticles for Enhanced Ferroptosis/Apoptosis Treatment of Hepatocellular Carcinoma. Adv Healthc Mater 14, e2401747 (2025).

[12]. Truchan, K., Zagrajczuk, B., Cholewa-Kowalska, K. & Osyczka, A. M. Rapid osteoinduction of human adipose-derived stem cells grown on bioactive surfaces and stimulated by chemically modified media flow. J Biol Eng 19, 23 (2025).

[13]. Bridgeman, C. J., Shah, S. A., Oakes, R. S. & Jewell, C. M. Dissecting regulatory T cell expansion using polymer microparticles presenting defined ratios of self-antigen and regulatory cues. Front Bioeng Biotechnol 11, 1184938 (2023).

[14]. Antioxidants: Classification, Natural Sources, Activity/Capacity Measurements, and Usefulness for the Synthesis of Nanoparticles. https: //www.mdpi.com/1996-1944/14/15/4135.

[15]. Nano-Radiopharmaceuticals in Colon Cancer: Current Applications, Challenges, and Future Directions. https: //www.mdpi.com/1424-8247/18/2/257.

[16]. Current Research Trends and Hotspots in Radiotherapy Combined with Nanomaterials for Cancer Treatment: A Bibliometric and Visualization Analysis. https: //www.mdpi.com/2079-4991/15/15/1205.

[17]. Pakulska, M. M. et al. Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles. Sci Adv 2, e1600519 (2016).

[18]. Leelakanok, N., Geary, S. & Salem, A. Fabrication and Use of Poly(d, l-lactide-co-glycolide)-Based Formulations Designed for Modified Release of 5-Fluorouracil. J Pharm Sci 107, 513–528 (2018).

[19]. Comparative Nanofabrication of PLGA-Chitosan-PEG Systems Employing Microfluidics and Emulsification Solvent Evaporation Techniques. https: //www.mdpi.com/2073-4360/12/9/1882.

[20]. Full article: Polymer-based prolonged-release nanoformulation of duloxetine: fabrication, characterization and neuropharmacological assessments. https: //www.tandfonline.com/doi/10.1080/03639045.2020.1851240?url_ver=Z39.88-2003& rfr_id=ori: rid: crossref.org& rfr_dat=cr_pub%20%200pubmed.

[21]. Tinsley-Bown, A. M., Fretwell, R., Dowsett, A. B., Davis, S. L., & G.H. Farrar. Formulation of poly(d, l-lactic-co-glycolic acid) microparticles for rapid plasmid DNA delivery. Journal of Controlled Release 66, 229–241 (2000).

[22]. Nath, S. D., Son, S., Sadiasa, A., Min, Y. K. & Lee, B. T. Preparation and characterization of PLGA microspheres by the electrospraying method for delivering simvastatin for bone regeneration. International Journal of Pharmaceutics 443, 87–94 (2013).

[23]. Yue, J., Liu, Z., Wang, L., Wang, M. & Pan, G. Recent advances in bioactive hydrogel microspheres: Material engineering strategies and biomedical prospects. Materials Today Bio 31, 101614 (2025).

[24]. Research Progress of Protein-Based Bioactive Substance Nanoparticles. https: //www.mdpi.com/2304-8158/12/16/2999.

[25]. Liu, Q. et al. Continuous preparation of long-acting hydromorphone PLGA microspheres using an automatic and scalable microfluidic process system. International Journal of Pharmaceutics 674, 125459 (2025).

[26]. Microfluidic preparation of monodisperse PLGA-PEG/PLGA microspheres with controllable morphology for drug release - Lab on a Chip (RSC Publishing). https: //pubs.rsc.org/en/content/articlelanding/2024/lc/d4lc00486h.

[27]. Xia, Y. et al. Liquid jet breakup: A new method for the preparation of poly lactic-co-glycolic acid microspheres. European Journal of Pharmaceutics and Biopharmaceutics 137, 140–147 (2019).

[28]. Müller-Ruch, U., Skorska, A., Lemcke, H., Steinhoff, G. & David, R. GLP: A requirement in cell therapies - perspectives for the cardiovascular field. Advanced Drug Delivery Reviews 165–166, 96–104 (2020).

[29]. Zhang, G. et al. Recent advances of nanoparticles on bone tissue engineering and bone cells. Nanoscale Adv 6, 1957–1973 (2024).

[30]. Guo, X. et al. Progress on liposome delivery systems in the treatment of bladder cancer. RSC Adv 15, 14315–14336 (2025).

[31]. Junyaprasert, V. B. & Thummarati, P. Innovative Design of Targeted Nanoparticles: Polymer-Drug Conjugates for Enhanced Cancer Therapy. Pharmaceutics 15, 2216 (2023).

[32]. Danhier, F. To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine? Journal of Controlled Release 244, 108–121 (2016).

[33]. Golombek, S. K. et al. Tumor targeting via EPR: Strategies to enhance patient responses. Advanced Drug Delivery Reviews 130, 17–38 (2018).

[34]. Progress and challenges towards targeted delivery of cancer therapeutics - PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC5897557/.

[35]. van der Meel, R. et al. Smart cancer nanomedicine. Nat. Nanotechnol. 14, 1007–1017 (2019).

[36]. Engineered Nanoparticles for Cancer Vaccination and Immunotherapy | Accounts of Chemical Research. https: //pubs.acs.org/doi/10.1021/acs.accounts.0c00456.

[37]. Li, Q. et al. Symphony of nanomaterials and immunotherapy based on the cancer–immunity cycle. Acta Pharmaceutica Sinica B 12, 107–134 (2022).

[38]. Nanoparticle-enhanced chemo-immunotherapy to trigger robust antitumor immunity | Science Advances. https: //www.science.org/doi/10.1126/sciadv.abc3646?url_ver=Z39.88-2003& rfr_id=ori: rid: crossref.org& rfr_dat=cr_pub%20%200pubmed.

[39]. Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis. https: //www.mdpi.com/1422-0067/24/14/11367.

[40]. Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies. https: //www.mdpi.com/2072-6694/13/11/2607.

[41]. Nagaraj, H. et al. Breaking the cellular delivery bottleneck: recent developments in direct cytosolic delivery of biologics. RSC Pharm 2, 850–864.

[42]. Cheng, Z. et al. Lipid-based nanosystems: the next generation of cancer immune therapy. J Hematol Oncol 17, 53 (2024).

[43]. Anbazhagan, M. K. & Mahalingam, S. Advancements in nanofibers and nanocomposites: Cutting-edge innovations for tissue engineering and drug delivery—A review. Sci Prog 108, 00368504241300842 (2025).

[44]. da Silva, A. F., Gonçalves, L. M. D., Fernandes, A. & Almeida, A. J. Optimization and evaluation of a chitosan-coated PLGA nanocarrier for mucosal delivery of Porphyromonas gingivalis antigens. European Journal of Pharmaceutical Sciences 202, 106896 (2024).

[45]. Yang, D. et al. Quaternized chitosan-coated PLGA nanoparticles co-deliver resveratrol and all-trans retinoic acid to enhance humoral immunity, cellular immunity and gastrointestinal mucosal immunity. Colloids and Surfaces B: Biointerfaces 256, 114994 (2025).

[46]. Yu, J. et al. Immunocytes in the tumor microenvironment: recent updates and interconnections. Front Immunol 16, 1517959 (2025).

[47]. Liu, X. et al. The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy. Front Oncol 11, 720842 (2021).

[48]. Lee, C. K. et al. Anti-PD-L1 F(ab) Conjugated PEG-PLGA Nanoparticle Enhances Immune Checkpoint Therapy. Nanotheranostics 6, 243–255 (2022).

[49]. Zhang, N. et al. Photothermal therapy mediated by phase-transformation nanoparticles facilitates delivery of anti-PD1 antibody and synergizes with antitumor immunotherapy for melanoma. Journal of Controlled Release 306, 15–28 (2019).

[50]. Immune checkpoint silencing using RNAi-incorporated nanoparticles enhances antitumor immunity and therapeutic efficacy compared with antibody-based approaches | Journal for ImmunoTherapy of Cancer. https: //jitc.bmj.com/content/10/2/e003928.

[51]. Han, Y., Tian, X., Zhai, J. & Zhang, Z. Clinical application of immunogenic cell death inducers in cancer immunotherapy: turning cold tumors hot. Front Cell Dev Biol 12, 1363121 (2024).

[52]. Cheng, C., Wang, Q. & Zhang, S. Synergy of oncolytic adenovirus and immune checkpoint inhibitors: transforming cancer immunotherapy paradigms. Front Immunol 16, 1610858 (2025).

[53]. Development of Toll-like Receptor Agonist-Loaded Nanoparticles as Precision Immunotherapy for Reprogramming Tumor-Associated Macrophages | ACS Applied Materials & Interfaces. https: //pubs.acs.org/doi/10.1021/acsami.1c01453.

[54]. Zhao, X. et al. Inducing enhanced immunogenic cell death with nanocarrier-based drug delivery systems for pancreatic cancer therapy. Biomaterials 102, 187–197 (2016).

[55]. Chen, P.-M. et al. Modulation of tumor microenvironment using a TLR-7/8 agonist-loaded nanoparticle system that exerts low-temperature hyperthermia and immunotherapy for in situ cancer vaccination. Biomaterials 230, 119629 (2020).

[56]. Wang, B. et al. Advances in immunotherapy and targeted therapy for advanced clear-cell renal cell carcinoma: current strategies and future directions. Front Immunol 16, 1582887 (2025).

[57]. Li, X., Song, R., Zhu, J., He, J. & Liu, X. A multidimensional analysis and future perspectives of cellular cancer vaccines. Biochem Biophys Res Commun 780, 152380 (2025).

[58]. Dölen, Y. et al. PLGA Nanoparticles Co-encapsulating NY-ESO-1 Peptides and IMM60 Induce Robust CD8 and CD4 T Cell and B Cell Responses. Front Immunol 12, 641703 (2021).

[59]. Creemers, J. H. A. et al. Assessing the safety, tolerability and efficacy of PLGA-based immunomodulatory nanoparticles in patients with advanced NY-ESO-1-positive cancers: a first-in-human phase I open-label dose-escalation study protocol. BMJ Open 11, e050725 (2021).

[60]. Chen, Q. et al. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat Commun 7, 13193 (2016).

[61]. Hybrid nanovaccine for the co-delivery of the mRNA antigen and adjuvant - Nanoscale (RSC Publishing). https: //pubs.rsc.org/en/content/articlelanding/2019/nr/c9nr05475h.

[62]. Koerner, J., Horvath, D. & Groettrup, M. Harnessing Dendritic Cells for Poly (D, L-lactide-co-glycolide) Microspheres (PLGA MS)—Mediated Anti-tumor Therapy. Front Immunol 10, 707 (2019).

[63]. Koerner, J. et al. PLGA-particle vaccine carrying TLR3/RIG-I ligand Riboxxim synergizes with immune checkpoint blockade for effective anti-cancer immunotherapy. Nat Commun 12, 2935 (2021).

[64]. Suxin, L., Bennett, Z. T., Sumer, B. D. & Gao, J. Nano-Immune-Engineering Approaches to Advance Cancer Immunotherapy: Lessons from Ultra-pH-Sensitive Nanoparticles. Acc Chem Res 53, 2546–2557 (2020).

Cite this article

Gan,Z. (2025). PLGA Nanoparticle in Tumor Immunotherapy: Advances in Research and Application. Theoretical and Natural Science,152,24-33.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

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Volume title: Proceedings of ICMMGH 2026 Symposium: Biomedical Imaging and AI Applications in Neurorehabilitation

ISBN: 978-1-80590-565-3(Print) / 978-1-80590-566-0(Online)
Editor: Sheiladevi Sukumaran, Alan Wang
Conference website: https://www.icmmgh.org/auckland.html
Conference date: 14 November 2025
Series: Theoretical and Natural Science
Volume number: Vol.152
ISSN: 2753-8818(Print) / 2753-8826(Online)

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