Nanostructured Drug Delivery Systems in Immunotherapy: An Updated Overview of Nanotechnology-Based Therapeutic Innovations
Source abstract
Abstract
Using nanostructured drug delivery systems has attracted increasing interest in immunotherapeutic approaches. The intrinsic immunomodulatory properties and versatility of nanoparticles used as carriers were consistently reported to augment treatment efficiency as nanoscaled materials increase drug accumulation at the desired site, enhance cell internalization, and improve therapeutic outcomes. Thus, numerous studies have exploited the potential use of nanostructured drug delivery vehicles in delivering different cargo as a promising alternative for treating conditions like cancer, autoimmune diseases, infectious diseases, and allergic and immune disorders. In this context, this paper presents nanostructured drug delivery systems as a solid basis for immunotherapeutic innovations, highlighting their advantages for improving treatment strategies, reviewing their clinical applications, and discussing existing challenges and ways to overcome them.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Nanoparticle-Based Drug Delivery · Nanoplatforms for cancer theranostics · RNA Interference and Gene Delivery
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania
Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050657 Bucharest, Romania
Faculty of Chemical Engineering and Biotechnology, National University of Science and Technology Politehnica Bucharest, 011061 Bucharest, Romania
References (100+)
Show source-provided references
1. Immune Evasion, Immunopathology and the Regulation of the Immune System10.3390/pathogens2010071 ↗
2. Mitarotonda, R., Giorgi, E., Eufrasio-da-Silva, T., Dolatshahi-Pirouz, A., Mishra, Y.K., Khademhosseini, A., Desimone, M.F., De Marzi, M., and Orive, G. (2022). Immunotherapeutic nanoparticles: From autoimmune disease control to the development of vaccines. Biomater. Adv., 135.10.1016/j.bioadv.2022.212726 ↗
3. Advances in carbon nanomaterials for immunotherapy10.1016/j.apmt.2022.101397 ↗
4. Dysregulation of the adaptive immune system in patients with early-stage Parkinson disease10.1212/NXI.0000000000001036 ↗
5. Immune dysregulation10.1016/j.jaci.2022.11.001 ↗
6. Immune evasion in cancer: Mechanistic basis and therapeutic strategies10.1016/j.semcancer.2015.03.004 ↗
7. Vaillant, A.A.J., and Qurie, A. (2023). Immunodeficiency. StatPearls, StatPearls Publishing.
8. Nanoparticles for Immunotherapy10.1016/B978-0-08-102828-5.00011-5 ↗
9. Engineering nanoparticles to overcome barriers to immunotherapy10.1002/btm2.10005 ↗
10. Employing drug delivery strategies to overcome challenges using TLR7/8 agonists for cancer immunotherapy10.1208/s12248-021-00620-x ↗
11. Primary, adaptive, and acquired resistance to cancer immunotherapy10.1016/j.cell.2017.01.017 ↗
12. Dobosz, P., Stępień, M., Golke, A., and Dzieciątkowski, T. (2022). Challenges of the Immunotherapy: Perspectives and Limitations of the Immune Checkpoint Inhibitor Treatment. Int. J. Mol. Sci., 23.10.3390/ijms23052847 ↗
13. Recent advances in primary resistance mechanisms against immune checkpoint inhibitors10.1097/CCO.0000000000000802 ↗
14. Defining tumor resistance to PD-1 pathway blockade: Recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce10.1136/jitc-2019-000398 ↗
15. Amphiphilic poly (esteracetal) s as dual pH-and enzyme-responsive micellar immunodrug delivery systems10.1039/C9PY01716J ↗
16. Croitoru, G.-A., Pîrvulescu, D.-C., Niculescu, A.-G., Epistatu, D., Rădulescu, M., Grumezescu, A.M., and Nicolae, C.-L. (2024). Nanomaterials in Immunology: Bridging Innovative Approaches in Immune Modulation, Diagnostics, and Therapy. J. Funct. Biomater., 15.10.3390/jfb15080225 ↗
17. Salem, S.S., Hammad, E.N., Mohamed, A.A., and El-Dougdoug, W. (2022). A comprehensive review of nanomaterials: Types, synthesis, characterization, and applications. Biointerface Res. Appl. Chem., 13.10.33263/BRIAC131.041 ↗
18. Intravenously delivered graphene nanosheets and multiwalled carbon nanotubes induce site-specific Th2 inflammatory responses via the IL-33/ST2 axis
19. Explicating the applications of quality by design tools in optimization of microparticles and nanotechnology based drug delivery systems
20. A review on synthesis of silver nanoparticles and their biomedical applications
21. Horwitz, D.A., Bickerton, S., and La Cava, A. (2021). Strategies to use nanoparticles to generate CD4 and CD8 regulatory T cells for the treatment of SLE and other autoimmune diseases. Front. Immunol., 12.10.3389/fimmu.2021.681062 ↗
22. Current Trends and Challenges in Pharmacoeconomic Aspects of Nanocarriers as Drug Delivery Systems for Cancer Treatment10.2147/IJN.S323831 ↗
23. Nanocarriers for targeted drug delivery10.1016/j.jddst.2021.102426 ↗
24. Nano-based drug delivery systems: Conventional drug delivery routes, recent developments and future prospects10.1016/j.medidd.2022.100134 ↗
25. Radzi, M.R.M., Lim, C.K., Sulaiman, N., and Jemon, K. (2023). Nanoparticles-based Chemo-Phototherapy Synergistic Effects for Breast Cancer Treatment: A Systematic Review. Biointerface Res. Appl. Chem., 13.10.33263/BRIAC133.232 ↗
26. Nanoparticles for Cancer Diagnosis, Radionuclide Therapy and Theranostics10.1021/acsnano.1c09139 ↗
27. Liu, J., Liu, Z., Pang, Y., and Zhou, H. (2022). The interaction between nanoparticles and immune system: Application in the treatment of inflammatory diseases. J. Nanobiotechnol., 20.10.1186/s12951-022-01343-7 ↗
28. Nanoparticles design considerations to co-deliver nucleic acids and anti-cancer drugs for chemoresistance reversal
29. Stimuli-Responsive Nanoparticles for Controlled Drug Delivery in Synergistic Cancer Immunotherapy10.1002/advs.202103444 ↗
30. Mechanisms of immune response to inorganic nanoparticles and their degradation products10.1016/j.addr.2021.114022 ↗
31. Immunotoxicity of metal and metal oxide nanoparticles: From toxic mechanisms to metabolism and outcomes10.1039/D3BM00271C ↗
32. Ahamad, N., Kar, A., Mehta, S., Dewani, M., Ravichandran, V., Bhardwaj, P., Sharma, S., and Banerjee, R. (2021). Immunomodulatory nanosystems for treating inflammatory diseases. Biomaterials, 274.10.1016/j.biomaterials.2021.120875 ↗
33. Niculescu, A.-G., and Grumezescu, A.M. (2021). Polymer-Based Nanosystems—A Versatile Delivery Approach. Materials, 14.10.3390/ma14226812 ↗
34. Yu, Z., Shen, X., Yu, H., Tu, H., Chittasupho, C., and Zhao, Y. (2023). Smart Polymeric Nanoparticles in Cancer Immunotherapy. Pharmaceutics, 15.10.3390/pharmaceutics15030775 ↗
35. Application of polymeric nanoparticles in immunotherapy10.1097/ACI.0b013e3283588c57 ↗
36. Lipid nanoparticles for nucleic acid delivery: Current perspectives10.1016/j.addr.2020.06.002 ↗
37. Aldosari, B.N., Alfagih, I.M., and Almurshedi, A.S. (2021). Lipid nanoparticles as delivery systems for RNA-based vaccines. Pharmaceutics, 13.10.3390/pharmaceutics13020206 ↗
38. Niculescu, A.-G., Bîrcă, A.C., and Grumezescu, A.M. (2021). New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery. Pharmaceutics, 13.10.3390/pharmaceutics13122053 ↗
39. Lipid nanoparticle-based mRNA delivery systems for cancer immunotherapy10.1186/s40580-023-00385-3 ↗
40. Wang, H.-L., Wang, Z.-G., and Liu, S.-L. (2022). Lipid Nanoparticles for mRNA Delivery to Enhance Cancer Immunotherapy. Molecules, 27.10.3390/molecules27175607 ↗
41. Wu, L., Li, X., Qian, X., Wang, S., Liu, J., and Yan, J. (2024). Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity. Vaccines, 12.10.3390/vaccines12020186 ↗
42. Nanotechnology in the COVID-19 era: Carbon-based nanomaterials as a promising solution10.1016/j.carbon.2023.118058 ↗
43. Recent progress of graphene oxide as a potential vaccine carrier and adjuvant10.1016/j.actbio.2020.06.009 ↗
44. Multifunctional Carbon-Based Nanoparticles: Theranostic Applications in Cancer Therapy and Diagnosis10.1021/acsabm.2c01000 ↗
45. Revolutionizing cancer therapy using tetrahedral DNA nanostructures as intelligent drug delivery systems10.1039/D4NA00145A ↗
46. Durbin, J.K., Miller, D.K., Niekamp, J., and Khisamutdinov, E.F. (2019). Modulating Immune Response with Nucleic Acid Nanoparticles. Molecules, 24.10.3390/molecules24203740 ↗
47. Ponchon, L. (2015). Simple Method for Constructing RNA Triangle, Square, Pentagon by Tuning Interior RNA 3WJ Angle from 60° to 90° or 108°. RNA Scaffolds: Methods and Protocols, Springer New York.
48. Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles10.1093/nar/gku516 ↗
49. In vitro assembly of cubic RNA-based scaffolds designed in silico10.1038/nnano.2010.160 ↗
50. Afonin, K.A., Kasprzak, W., Bindewald, E., Puppala, P.S., Diehl, A.R., Hall, K.T., Kim, T.J., Zimmermann, M.T., Jernigan, R.L., and Jaeger, L. (2021). Computational and Experimental Characterization of RNA Cubic Nanoscaffolds. Therapeutic RNA Nanotechnology, Jenny Stanford Publishing.10.1201/9781003122005 ↗
51. Polyhedra Self-Assembled from DNA Tripods and Characterized with 3D DNA-PAINT10.1126/science.1250944 ↗
52. Fabrication of RNA 3D nanoprism for loading and protection of small RNAs and model drugs10.1002/adma.201603180 ↗
53. Grabow, W.W., Zakrevsky, P., Afonin, K.A., Chworos, A., Shapiro, B.A., and Jaeger, L. (2021). Self-Assembling RNA Nanorings Based on RNAI/II Inverse Kissing Complexes. Therapeutic RNA Nanotechnology, Jenny Stanford Publishing.
54. Triggered contraction of self-assembled micron-scale DNA nanotube rings10.1038/s41467-024-46339-z ↗
55. Developmental Self-Assembly of a DNA Ring with Stimulus-Responsive Size and Growth Direction10.1021/jacs.2c03853 ↗
56. DNA-Assembled Nanoparticle Rings Exhibit Electric and Magnetic Resonances at Visible Frequencies10.1021/nl5046473 ↗
57. Methods for construction and characterization of simple or special multifunctional RNA nanoparticles based on the 3WJ of phi29 DNA packaging motor10.1016/j.ymeth.2018.02.025 ↗
58. Covalent Hyperbranched Polymer Self-Assemblies of Three-Way Junction DNA for Single-Molecule Devices10.1021/acs.langmuir.0c01621 ↗
59. Nanosheets and 2D-nanonetworks by mutually assisted self-assembly of fullerene clusters and DNA three-way junctions10.1039/C9NA00485H ↗
60. Takezawa, Y., and Shionoya, M. (2020). Supramolecular DNA three-way junction motifs with a bridging metal center. Front. Chem., 7.10.3389/fchem.2019.00925 ↗
61. Ultrastable synergistic tetravalent RNA nanoparticles for targeting to cancers10.1016/j.nantod.2012.06.010 ↗
62. Target-Catalyzed DNA Four-Way Junctions for CRET Imaging of MicroRNA, Concatenated Logic Operations, and Self-Assembly of DNA Nanohydrogels for Targeted Drug Delivery10.1021/acsami.5b07827 ↗
63. Hybrid Nanomaterials for Cancer Immunotherapy10.1002/advs.202204932 ↗
64. Gautam, A., Beiss, V., Wang, C., Wang, L., and Steinmetz, N.F. (2021). Plant Viral Nanoparticle Conjugated with Anti-PD-1 Peptide for Ovarian Cancer Immunotherapy. Int. J. Mol. Sci., 22.10.3390/ijms22189733 ↗
65. Pruteanu, L.-L., Braicu, C., Módos, D., Jurj, M.-A., Raduly, L.-Z., Zănoagă, O., Magdo, L., Cojocneanu, R., Paşca, S., and Moldovan, C. (2022). Targeting Cell Death Mechanism Specifically in Triple Negative Breast Cancer Cell Lines. Int. J. Mol. Sci., 23.10.3390/ijms23094784 ↗
66. Yahya, S., Abdelmenym Mohamed, S.I., and Yahya, S. (2023). Gene Editing: A Powerful Tool for Cancer Immunotherapy. Biointerface Res. Appl. Chem., 13.10.33263/BRIAC131.098 ↗
67. Chen, C., Wang, Z., Ding, Y., and Qin, Y. (2023). Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma. Front. Immunol., 14.10.3389/fimmu.2023.1133308 ↗
68. Native Mitochondria-Targeting polymeric nanoparticles for mild photothermal therapy rationally potentiated with immune checkpoints blockade to inhibit tumor recurrence and metastasis10.1016/j.cej.2021.130171 ↗
69. Anti-PD-L1 F(ab) Conjugated PEG-PLGA Nanoparticle Enhances Immune Checkpoint Therapy10.7150/ntno.65544 ↗
70. Souza, A.O.D. (2023). Overview of nanomaterials and cellular interactions. Biointerface Res. Appl. Chem., 13.10.33263/BRIAC134.367 ↗
71. Effects of P-MAPA immunotherapy associated with gemcitabine on chemically-induced pancreatic cancer in animal model: New therapeutic perspectives
72. Development of thermosensitive resiquimod-loaded liposomes for enhanced cancer immunotherapy10.1016/j.jconrel.2020.11.013 ↗
73. Park, W., Heo, Y.-J., and Han, D.K. (2018). New opportunities for nanoparticles in cancer immunotherapy. Biomater. Res., 22.10.1186/s40824-018-0133-y ↗
74. Green solvents tailored nanostructures of block copolymers and their potential applications in drug delivery10.1016/j.molliq.2024.125642 ↗
75. In vivo evaluation of antitumoral and antiangiogenic effect of imiquimod-loaded polymeric nanoparticles10.1016/j.biopha.2018.04.079 ↗
76. New pectin-based hydrogel containing imiquimod-loaded polymeric nanocapsules for melanoma treatment10.1007/s13346-020-00805-5 ↗
77. Anti-HPV Nanoemulsified-Imiquimod: A New and Potent Formulation to Treat Cervical Cancer10.1208/s12249-019-1558-x ↗
78. TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy10.1038/s41551-018-0236-8 ↗
79. Polymer-based nanoparticles loaded with a TLR7 ligand to target the lymph node for immunostimulation10.1016/j.ijpharm.2017.11.031 ↗
80. Komura, F., Okuzumi, K., Takahashi, Y., Takakura, Y., and Nishikawa, M. (2020). Development of RNA/DNA Hydrogel Targeting Toll-Like Receptor 7/8 for Sustained RNA Release and Potent Immune Activation. Molecules, 25.10.3390/molecules25030728 ↗
81. Niculescu, A.-G., and Grumezescu, A.M. (2022). Novel Tumor-Targeting Nanoparticles for Cancer Treatment—A Review. Int. J. Mol. Sci., 23.10.3390/ijms23095253 ↗
82. Tampucci, S., Guazzelli, L., Burgalassi, S., Carpi, S., Chetoni, P., Mezzetta, A., Nieri, P., Polini, B., Pomelli, C.S., and Terreni, E. (2020). pH-Responsive Nanostructures Based on Surface Active Fatty Acid-Protic Ionic Liquids for Imiquimod Delivery in Skin Cancer Topical Therapy. Pharmaceutics, 12.10.3390/pharmaceutics12111078 ↗
83. TLR7/8 Agonist-Loaded Nanoparticles Augment NK Cell-Mediated Antibody-Based Cancer Immunotherapy10.1021/acs.molpharmaceut.0c00271 ↗
84. Photothermally activatable PDA immune nanomedicine combined with PD-L1 checkpoint blockade for antimetastatic cancer photoimmunotherapy10.1039/C9TB00089E ↗
85. Multifunctional Nanoparticle Loaded Injectable Thermoresponsive Hydrogel as NIR Controlled Release Platform for Local Photothermal Immunotherapy to Prevent Breast Cancer Postoperative Recurrence and Metastases10.1002/adfm.202001059 ↗
86. Bacterial Vesicle-Cancer Cell Hybrid Membrane-Coated Nanoparticles for Tumor Specific Immune Activation and Photothermal Therapy10.1021/acsami.0c13169 ↗
87. Cancer-Erythrocyte Hybrid Membrane-Camouflaged Magnetic Nanoparticles with Enhanced Photothermal-Immunotherapy for Ovarian Cancer10.1021/acsnano.1c07180 ↗
88. Tumor-Associated-Macrophage-Membrane-Coated Nanoparticles for Improved Photodynamic Immunotherapy10.1021/acs.nanolett.1c00818 ↗
89. An Antigen-Delivery Protein Nanoparticle Combined with Anti-PD-1 Checkpoint Inhibitor Has Curative Efficacy in an Aggressive Melanoma Model10.1002/adtp.202000122 ↗
90. Mechanisms of immune evasion in bladder cancer10.1007/s00262-019-02443-4 ↗
91. A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer10.1126/sciadv.aaw6071 ↗
92. Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy10.1038/s41467-021-27434-x ↗
93. Polydopamine as the Antigen Delivery Nanocarrier for Enhanced Immune Response in Tumor Immunotherapy10.1021/acsbiomaterials.9b00359 ↗
94. Sordo-Bahamonde, C., Lorenzo-Herrero, S., Gonzalez-Rodriguez, A.P., Martínez-Pérez, A., Rodrigo, J.P., García-Pedrero, J.M., and Gonzalez, S. (2023). Chemo-Immunotherapy: A New Trend in Cancer Treatment. Cancers, 15.10.3390/cancers15112912 ↗
95. Chemotherapeutic drug-induced immunogenic cell death for nanomedicine-based cancer chemo–immunotherapy10.1039/D1NR05512G ↗
96. A Review on Nano-Based Drug Delivery System for Cancer Chemoimmunotherapy10.1007/s40820-020-00482-6 ↗
97. pH/Redox Dual-Responsive Polyplex with Effective Endosomal Escape for Codelivery of siRNA and Doxorubicin against Drug-Resistant Cancer Cells10.1021/acsami.9b02016 ↗
98. A different approach to immunochemotherapy for colon Cancer: Development of nanoplexes of cyclodextrins and Interleukin-2 loaded with 5-FU10.1016/j.ijpharm.2022.121940 ↗
99. NLG919/cyclodextrin complexation and anti-cancer therapeutic benefit as a potential immunotherapy in combination with paclitaxel10.1016/j.ejps.2019.105034 ↗
100. Zhou, W., Zhou, Y., Chen, X., Ning, T., Chen, H., Guo, Q., Zhang, Y., Liu, P., Zhang, Y., and Li, C. (2021). Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment. Biomaterials, 268.10.1016/j.biomaterials.2020.120546 ↗