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Application of Nano-Delivery System in Tumor Immunotherapy

DOI: 10.12677/NAT.2023.134010, PP. 97-109

Keywords: 肿瘤,纳米递送,免疫治疗,理化性质<>br, Tumour, Nano-Delivery, Immunotherapy, Physico-chemical Properties

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Immunotherapy has become a powerful clinical strategy for the treatment of cancer. The number of approved immunotherapy drugs has been increasing, and many treatments have emerged in clinical and preclinical development. However, a key challenge to the widespread implementation of cancer immunotherapy remains the controlled regulation of the immune system, as these treatments have serious side effects, including autoim-munity and non-specific inflammation. Advanced biomaterials and drug delivery systems, such as nanoparticles and treatment with T cells, can effectively use immunotherapy and improve its effectiveness while reducing side effects. Here, we discuss the research progress, as well as the opportunities, challenges and applications of nano-delivery technology in tumor immunotherapy in order to improve the shortcomings of tumor immunotherapy.


[1]  Riley, R.S., June, C.H., Langer, R. and Mitchell, M.J. (2019) Delivery Technologies for Cancer Immunotherapy. Nature Reviews Drug Discovery, 18, 175-196.
[2]  Pardoll, D.M. (2012) The Blockade of Immune Checkpoints in Cancer Immunotherapy. Nature Reviews Cancer, 12, 252-264.
[3]  Webb, E.S., et al. (2017) Immune Checkpoint Inhibitors in Cancer Therapy. The Journal of Biomedical Research, 32, 317-326.
[4]  Granier, C., et al. (2017) Mechanisms of Action and Rationale for the Use of Checkpoint Inhibitors in Cancer. ESMO Open, 2, e000213.
[5]  Chakraborty, S. and Rahman, T. (2012) The Dif?culties in Cancer Treatment. Cancer Medical Science, 6, ed16.
[6]  Wheler, J., Lee, J.J. and Kurzrock, R. (2014) Unique Molecular Landscapes in Cancer: Implications for Individualized, Curated Drug Combinations. Cancer Research, 74, 7181-7184.
[7]  Song, Q., Zhang, G.F., et al. (2021) Rein-forcing the Combinational Immuno-Oncotherapy of Switching “Cold” Tumor to “Hot” by Responsive Penetrating Nano-gels. ACS Applied Materials & Interfaces, 13, 36824-36838.
[8]  Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A. and Bray, F. (2021) Global Cancer Statistics 2020: GLOBOCA Nestimates Of incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249.
[9]  Arbyn, M., Weiderpass, E., Bruni, L., de Sanjosé, S., Saraiya, M., Ferlay, J., et al. (2020) Estimates of Incidence and Mortality of Cervical Cancer in 2018: A Worldwide Analysis. The Lancet Global Health, 8, E191-E203.
[10]  Esfahani, K., Roudaia, L., Buhlaiga, N., Del Rincon, S.V., Papneja, N. and Miller Jr., W.H. (2020) A Review of Cancer Immunotherapy: From the Past, to the Present, to the Fu-ture. Current Oncology, 27, 87-97.
[11]  Binnewies, M., Roberts, E.W., Kersten, K., Chan, V., Fearon, D.F., Me-rad, M. and Coussens, L.M. (2018) Understanding the Tumor Immune Microenvironment (TIME) for Effective Therapy. Nature Medicine, 24, 541-550.
[12]  Veillette, A. and Davidson, D. (2018) Developing Combination Immunotherapies against Cancer That Make Sense. Science Immunology, 3, eaav1872.
[13]  Schreiber, R.D., Old, L.J. and Smyth, M.J. (2011) Cancer Im-munoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion. Science, 331, 1565-1570.
[14]  Croft, M. (2003) Co-Stimulatory Members of the TNFR Family: Keys to Effective T-Cell Immunity? Nature Reviews Immunology, 3, 609-620.
[15]  Yuan, C.S., Liu, Y., Wang, T., Sun, M.J. and Chen, X.G. (2020) Nanomateri-als as Smart Immunomodulator Delivery System for Enhanced Cancer Therapy. ACS Biomaterials Science & Engineer-ing, 6, 4774-4798.
[16]  Capretto, L., et al. (2013) Microfluidic and Lab-on-a-Chip Preparation Routes for Organic Nanoparticles and Vesicular Systems for Nanomedicine Applications. Advanced Drug Delivery Reviews, 65, 1496-1532.
[17]  Whitesides, G.M. (2006) The Origins and the Future of Microflu-idics. Nature, 442, 368-373.
[18]  Valencia, P.M., Farokhzad, O.C., Karnik, R. and Langer, R. (2012) Mi-crofluidic Technologies for Accelerating the Clinical Translation of Nanoparticles. Nature Nanotechnology, 7, 623-629.
[19]  Coelho, T., et al. (2013) Safety and Efficacy of RNAi Therapy for Transthyretin Amyloidosis. The New England Journal of Medicine, 369, 819-829.
[20]  曹雪涛. 医学免疫学[M]. 北京: 人民卫生出版社, 2013.
[21]  Fuchs, C.S., Fakih, M., Schwartzberg, L., Cohn, A.L., Yee, L., Dreisbach, L., et al. (2013) TRAIL Receptor Agonist Conatumumab with Modi?ed FOLFOX6 plus Bevacizumab for ?rst-Line Treatment of Metastatic Colorectal Cancer: A Randomized Phase 1b/2 Trial. Cancer, 119, 4290-4298.
[22]  Salgia, R., Patel, P., Bothos, J., Yu, W., Eppler, S., Hegde, P., et al. (2014) Phase I Dose-Escalation Study of Onartuzumab as a Single Agent and in Combination with Bevacizumab in Patients with Advanced Solid Malignancies. Clinical Cancer Re-search, 20, 1666-1675.
[23]  Windbergs, M., Zhao, Y.J., Hey-man, J. and Weitz, D.A. (2013) Biodegradable Core-Shell Carriers for Simultaneous Encapsulation of Synergistic Ac-tives. Journal of the American Chemical Society, 135, 7933-7937.
[24]  Jokerst, J.V., Lobovkina, T., Zare, R.N. and Gambhir, S.S. (2011) Nano-particle PEGylation for Imaging and Therapy. Nanomedicine, 6, 715-728.
[25]  Peracchia, M.T., et al. (1999) Visualization of in vitro Protein-Rejecting Properties of PEGylated Stealth? Polycyanoacrylate Nanoparticles. Biomaterials, 20, 1269-1275.
[26]  Radovic-Moreno, A.F., et al. (2012) Surface Charge-Switching Polymeric Nanoparticles for Bacterial Cell Wall-Targeted Delivery of Antibiotics. ACS Nano, 6, 4279-4287.
[27]  Maleki Vareki, S., Garrigós, C. and Duran, I. (2017) Bi-omarkers of Response to PD-1/PD-L1 Inhibition. Critical Reviews in Oncology/Hematology, 116, 116-124.
[28]  Hay, K.A., et al. (2017) Kinetics and Biomarkers of Severe Cytokine Release Syndrome after CD19 Chimericantigen Receptor—Modified T-Cell Therapy. Blood, 130, 2295-2306.
[29]  Schmidt, C. (2017) The Benefits of Immunotherapy Combina-tions. Nature, 552, S67-S69.
[30]  Riley, R.S. and Day, E.S. (2017) Gold Nanoparticle-Mediated Photothermal Therapy: Applications and Opportunities for Multimodal Cancer Treatment. WIREs Nanomedicine and Nanobiotechnology, 9, e1449.
[31]  Lee, S. and Margolin, K. (2011) Cytokines in Cancer Immunotherapy. Cancers, 3, 3856-3893.
[32]  Milling, L., Zhang, Y. and Irvine, D.J. (2017) Delivering Safer Im-munotherapies for Cancer. Advanced Drug Delivery Reviews, 114, 79-101.
[33]  June, C.H., Warshauer, J.T. and Bluestone, J.A. (2017) Is Auto-immunity the Achilles’ Heel of Cancer Immunotherapy? Nature Medicine, 23, 540-547.
[34]  Zhang, Y., Li, N., Suh, H. and Irvine, D.J. (2018) Nanoparticle Anchoring Targets Immune Agonists to Tumors Enabling Anti-Cancer Immunity without Systemic Toxicity. Nature Communica-tions, 9, Article No. 6.
[35]  Wilson, J.T., Keller, S., Manganiello, M.J., Cheng, C., Lee, C.C., Opara, C., Convertine, A. and Stayton, P.S. (2013) pH-Responsive Nanoparticle Vaccines for Dual-Delivery of Antigens and Immunostimulatory Oligonucleotides. ACS Nano, 7, 3912-3925.
[36]  Maeda, H., Nakamura, H. and Fang, J. (2013) The EPR Effect for Mac-romolecular Drug Delivery to Solid Tumors: Improvement of Tumor uptake, Lowering of Systemic Toxicity, and Distinct Tumor Imaging in vivo. Advanced Drug Delivery Reviews, 65, 71-79.
[37]  Shukla, S. and Steinmetz, N.F. (2016) Emerging Nanotechnologies for Cancer Immunotherapy. Experimental Biology and Medicine, 241, 1116-1126.
[38]  Zang, X., Zhao, X., Hu, H., Qiao, M., Deng, Y. and Chen, D. (2017) Nanoparticles for Tumor Immunotherapy. European Journal of Pharmaceutics and Biopharmaceutics, 115, 243-256.
[39]  Hu, Q., Sun, W., Wang, C. and Gu, Z. (2016) Recent Advances of Cocktail Chemotherapy by Combination Drug Delivery Systems. Advanced Drug Delivery Reviews, 98, 19-34.
[40]  Pacardo, D.B., Ligler, F.S. and Gu, Z. (2015) Programma-ble Nanomedicine: Synergistic and Sequential Drug Delivery Systems. Nanoscale, 7, 3381-3391.
[41]  Langer, R. and Peppas, N.A. (2003) Advances in Biomaterials, Drug Delivery, and Bionanotechnology. AIChE Journal, 49, 2990-3006.
[42]  Xie, Z., Su, Y., Kim, G.B., Selvi, E., Ma, C., Aragon-San-abria, V., Hsieh, J.T., Dong, C. and Yang, J. (2017) Immune Cell-Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery. Small, 13, Article ID: 1603121.
[43]  Kamaly, N., et al. (2012) Targeted Polymeric Therapeu-tic Nanoparticles: Design, Development and Clinical Translation. Chemical Society Reviews, 41, 2971-3010.
[44]  Acharya, S. and Sahoo, S.K. (2011) PLGA Nanoparticles Containing Various Anticancer Agents and Tumour Delivery by EPR Effect. Advanced Drug Delivery Reviews, 63, 170-183.
[45]  Bertrand, N., et al. (2014) Cancer Nanotechnology: The Impact of Passive and Active Targeting in the Era of Modern Cancer Biology. Advanced Drug Delivery Reviews, 66, 2-25.
[46]  Chauhan, V.P., et al. (2012) Normalization of Tumour Blood Ves-sels Improves the Delivery of Nanomedicines in a Size-Dependent Manner. Nature Nanotechnology, 7, 383-388.
[47]  Monsky, W.L., et al. (1999) Augmentation of Transvascular Transport of Macromolecules and Nanoparticlesin Tumors Using Vascular Endothelial Growth Factor. Cancer Research, 59, 4129-4135.
[48]  Danquah, M.K., Zhang, X.A. and Mahato, R.I. (2011) Extravasation of Polymeric Nanomedicines across Tumor Vasculature. Advanced Drug Delivery Reviews, 63, 623-639.
[49]  Zhang, X.Q., et al. (2012) Interactions of Nanomaterials and Bio-logical Systems: Implications to Personalized Nanomedicine. Advanced Drug Delivery Reviews, 64, 1363-1384.
[50]  Peer, D., et al. (2007) Nanocarriers as an Emerging Platform for Cancer Therapy. Nature Nanotechnology, 2, 751-760.
[51]  Ge, Z. and Liu, S. (2013) Functional Block Copolymer Assemblies Responsive to Tumor and Intracellular Microenvironments for Site-Specific Drug Delivery and Enhanced Imaging Per-formance. Chemical Society Reviews, 42, 7289- 7325.
[52]  Valencia, P.M., et al. (2011) Effects of Ligands with Different Water Solubilities on Self-Assembly and Properties of Targeted Nanoparti-cles. Biomaterials, 32, 6226-6233.
[53]  Decuzzi, P., Lee, S., Bhushan, B. and Ferrari, M. (2005) A Theoretical Model for the Margination of Particles within Blood Vessels. Annals of Biomedical Engineering, 33, 179-190.
[54]  Guo, Y.F., Zhao, S., Qiu, H.H., Wang, T., Zhao, Y.N., Han, M.H., Dong, Z.Q. and Wang, X.T. (2018) Shape of Nanoparticles as a Design Parameter to Improve Docetaxel Antitumor Efficacy. Bioconjugate Chemistry, 29, 1302-1311.
[55]  He, C.B., Hu, Y.P., Yin, L.C., Tang, C. and Yin, C.H. (2010) Effects of Particle Size and Surface Charge on Cellular uptake and Biodistribution of Polymeric Nanoparticles. Biomaterials, 31, 3657-3666.
[56]  Chen, X.J., Zhang, X.Q., Tang, M.X., Liu, Q. and Zhou, G. (2020) Anti-PD-L1-Modified and ATRA-Loaded Nanoparticles for Immuno-Treatment of Oral Dysplasia and Oral Squamous Cell Carcinoma. Nanomedicine, 15, 951-968.
[57]  Liu, Y., Chen, X.G., Yang, P.P., Qiao, Z.Y. and Wang, H. (2019) Tumor Microenvironmental pH and Enzyme Dual Responsive Polymer-Liposomes for Synergistic Treatment of Cancer Immuno-Chemotherapy. Biomacromolecules, 20, 882-892.
[58]  Leamon, C.P., Cooper, S.R. and Hardee, G.E. (2003) Fo-late-Liposome-Mediated Antisense Oligodeoxynucleotide Targeting to Cancer Cells: Evaluation in Vitro and in Vivo. Bi-oconjugate Chemistry, 14, 738-747.
[59]  Lu, W., Xiong, C.Y., Zhang, R., Shi, L.F., Huang, M., Zhang, G.D., Song, S.L., Huang, Q., Liu, G.Y. and Li, C. (2012) Receptor-Mediated Transcytosis: A Mechanism for Active Extravascular Transport of Nanoparticles in Solid Tumors. Journal of Controlled Release, 161, 959-966.
[60]  Zhang, L., Hao, P.Y., Yang, D.J., Feng, S., Peng, B., et al. (2019) Designing Nanoparticles with Improved Tumor Penetration: Surface Properties from the Molecular Architecture Viewpoint. Journal of Materials Chemistry B, 7, 953- 964.
[61]  Saha, K., Rahimi, M., Yazdani, M., Kim, S.T., Moyano, D.F., Hou, S., Das, R., Mout, R., Rezaee, F., Mahmoudi, M. and Rotello, V.M. (2016) Regulation of Macrophage Recognition through the Interplay of Nanoparticle Surface Functionality and Protein Corona. ACS Nano, 10, 4421-4430.
[62]  Yan, Y., Gause, K.T., Kamphuis, M.M.J., Ang, C.S., O’brien-Simpson, N.M., Lenzo, J.C., Reynolds, E.C., Nice, E.C. and Caruso, F. (2013) Differential Roles of the Proteincorona in the Cellular Uptake of Nanoporous Polymerparticles by Monocyte and Macro-phage Cell Lines. ACS Nano, 7, 10960-10970.
[63]  Yang, M.Y., Yu, L.X., Guo, R.W., Dong, A.J., Lin, C.G. and Zhang, J.H. (2018) A Modular Coassembly Approach to All-In-One Multifunc-tional Nanoplatform for Synergistic Codelivery of Doxorubicin and Curcumin. Nanomaterials, 8, Article 167.
[64]  Zhang, M.K., Wang, X.G., Zhu, J.Y., Liu, M.D., Li, C.X., Feng, J. and Zhang, X.Z. (2018) Double-Targeting Explosible Nanofirework for Tumor Ignition to Guide Tumor-Depth Photothermal Therapy. Small, 14, Article ID: 1800292.
[65]  Wang, J. (2017) Spatial Targeting of Tumor-Associated Macrophage and Tumor Cells with a Designer Nanocarrier for Cancer Chemo-Immunotherapy. 2017 39th Annual International Con-ference of the IEEE Engineering in Medicine and Biology Society (EMBC), Jeju, 11-15 July 2017, 291.
[66]  Christina, V., Gabriel, H., Bruce, G. and Francesco, P. (2015) A Mechanistic Tumor Penetration Model to Guide Antibody Drug Conjugate Design. PLOS ONE, 10, e0118977.
[67]  Ozcelikkale, A., Moon, H.R., Linnes, M. and Han, B. (2017) In Vitro Microfluidic Models of Tumor Microenvironment to Screen Transport of Drugs and Nanoparticles. WIREs Nano-medicine and Nanobiotechnology, 9, e1460.
[68]  Li, H.J., Du, J.Z., Liu, J., Du, X.J., Shen, S., et al. (2016) Smart Su-per-Structures with Ultrahigh pH-Sensitivity for Targeting Acidic Tumor Microenvironment: Instantaneous Size Switch-ing and Improved Tumor Penetration. ACS Nano, 10, 6753-6761.
[69]  Jiang, T., Sun, W., Zhu, Q., Burns, N.A., Khan, S.A., Mo, R. and Gu, Z. (2015) Furin-Mediated Sequential Delivery of Anticancer Cytokine and Small-Molecule Drug Shuttled by Gra-phene. Advanced Materials, 27, 1021-1028.
[70]  Hu, X.X., Wang, Y. and Peng, B. (2014) Chitosan-Capped Meso-porous Silica Nanoparticles as pH-Responsive Nanocarriers for Controlled Drug Release. Chemistry—An Asian Journal, 9, 319-327.
[71]  Slowing, I.I., Vivero-Escoto, J.L., Wu, C.W. and Lin, V.S.Y. (2008) Mesoporous Silica Nanoparticles as Controlled Release Drug Delivery and Gene Transfection Carriers. Advanced Drug Delivery Reviews, 60, 1278-1288.
[72]  Ou, W., Byeon, J.H., Thapa, R.K., Ku, S.K., Yong, C.S. and Kim, J.O. (2018) Plug-and-Play Nanorization of Coarse Black Phosphorus for Targeted Chemo-Photoimmunotherapy of Col-orectal Cancer. ACS Nano, 12, 10061-10074.
[73]  Bobo, D., Robinson, K.J., Islam, J., Thurecht, K.J. and Corrie, S.R. (2016) Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date. Pharmaceu-tical Research, 33, 2373-2387.
[74]  Shao, J., Xie, H., Huang, H., Li, Z., Sun, Z., et al. (2016) Biode-gradable Black Phosphorus-Based Nanospheres for in vivo Photothermal Cancer Therapy. Nature Communications, 7, Article No. 12967.
[75]  Chen, W., Ouyang, J., Liu, H., Chen, M., et al. (2017) Black Phos-phorus Nanosheet-Based Drug Delivery System for Synergistic Photodynamic/Photothermal/Chemotherapy of Cancer. Advanced Materials, 29, Article ID: 1603864.
[76]  Wu, X., Wu, Y., Ye, H., Yu, S., He, C. and Chen, X. (2017) Inter-leukin-15 and Cisplatin Co-Encapsulated Thermosensitive Polypeptide Hydrogels for Combined Immuno-Chemotherapy. Journal of Controlled Release, 255, 81-93.
[77]  Lee, S. and Margolin, K. (2011) Cytokines in Cancer Immuno-therapy. Cancers, 3, 3856-3893.
[78]  Dudley, M.E. and Rosenberg, S.A. (2007) Adoptive Cell Transfer Therapy. Seminars in Oncology, 34, 524-531.
[79]  Dehaini, D., Fang, R.H. and Zhang, L. (2016) Biomimetic Strategies for Targeted Nanoparticle Delivery. Bioengineering & Translational Medicine, 1, 30-46.
[80]  Eralp, Y., Wang, X., Wang, J.P., Maughan, M.F. and Polo, J.M. (2004) Doxorubicin and Paclitaxel Enhance the Antitumor Efficacy of Vaccines Directed against HER2/Neu in a Murine Mam-mary Carcinoma Model. Breast Cancer Research, 6, Article No. R275.
[81]  Song, Q., Yin, Y., Shang, L., Wu, T., Zhang, D., et al. (2017) Tumor Microenvironment Responsive Nanogel for the Combi-natorial Antitumor Effect of Chemotherapy and Immunotherapy. Nano Letters, 17, 6366-6375.
[82]  Kuai, R., Yuan, W.M., Son, S., Nam, J., Xu, J., Fan, Y.C., Schwendeman, A. and Moon, J.J. (2018) Elimination of Established Tumors with Nanodisc-Based Combination Chemoimmunotherapy. Science Advances, 4, eaao1736.
[83]  Kemp, J.A., Shim, M.S., Heo, C.Y. and Kwon, Y.J. (2016) “Combo” Nanomedicine: Co-Delivery of Multi-Modal Therapeutics for Efficient, Targeted, and Safe Cancer Therapy. Advanced Drug Delivery Reviews, 98, 3-18.
[84]  Guo, C.L., Chen, Y.A., Gao, W.J., Chang, A.T., Ye, Y.J., et al. (2017) Liposomal Nanoparticles Carrying Anti-IL6R Antibody to the Tumour Microenvironment Inhibit Metastasis in Two Molecular Subtypes of Breast Cancer Mouse Models. Theranostics, 7, 775-788.
[85]  Zhang, B., Wang, T., Yang, S., Xiao, Y., Song, Y., Zhang, N. and Garg, S. (2016) Development and Evaluation of Oxaliplatin Andirinotecan Co-Loaded Liposomes for Enhanced Colorectal Cancer Therapy. Journal of Controlled Release, 238, 10-21.
[86]  Wei, J., Long, Y., Guo, R., Liu, X.L., Tang, X., et al. (2019) Multifunctional Polymeric Micelle-Based Chemo-Immu- no-therapy with Immune Checkpoint Blockade for Efficient Treatment of Orthotopic and Metastatic Breast Cancer. Acta Pharmaceutica Sinica B, 9, 819-831.
[87]  Gu, Z., Wang, Q., Shi, Y., Huang, Y., Zhang, J., Zhang, X. and Lin, G. (2018) Nanotechnology-Mediated Immunochemotherapy Combined with Docetaxel and PD-L1 Antibody Increase Therapeutic Effects and Decrease Systemic Toxicity. Journal of Controlled Re-lease, 286, 369-380.
[88]  Hernandez-Gil, J., Cobaleda-Siles, M., Za-baleta, A., Salassa, L., Calvo, J. and Mareque-Rivas, J.C. (2015) An Iron Oxide Nanocarrier Loaded with a Pt (IV) Pro-drug and Immunostimulatory dsRNA for Combining Complementary Cancer Killing Effects. Advanced Healthcare Ma-terials, 4, 1034-1042.
[89]  Lee, I.H., An, S., Yu, M.K., Kwon, H.K., Im, S.H. and Jon, S. (2011) Targeted Chemoimmunotherapy Using Drug- Loaded Aptamer-Dendrimer Bioconjugates. Journal of Controlled Release, 155, 435-441.
[90]  Chen, L., Zhou, L.L., Wang, C.H., Han, Y., Lu, Y.L., et al. (2019) Tumor-Targeted Drug and CpG Delivery System for Phototherapy and Docetaxel-Enhanced Immunotherapy with Polarization toward M1-Type Macrophages on Triple Negative Breast Cancers. Advanced Materials, 31, Article ID: 1904997.
[91]  Kadiyala, P., Li, D., Nunez, F.M., Altshuler, D., Doherty, R., et al. (2019) High-Density Lipoprotein-Mimicking Nanodiscs for Chemo-Immunotherapy against Glioblastoma Mul-tiforme. ACS Nano, 13, 1365-1384.
[92]  Kataoka, K., Harada, A. and Nagasaki, Y. (2001) Block Copolymer Micelles for Drug Delivery: Design, Characterization and Biological Significance. Advanced Drug Delivery Reviews, 47, 113-131.
[93]  Makadia, H.K. and Siegel, S.J. (2011) Poly Lac-tic-Co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers, 3, 1377-1397.
[94]  Gref, R., Minamitake, Y., Peracchia, M.T., Trubetskoy, V., Torchilin, V. and Langer, R. (1994) Biodegradable Long- Circulating Polymeric Nanospheres. Science, 263, 1600-1603.


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