pH-Responsive Poly(d,l-lactic-co-glycolic acid) Nanoparticles with Rapid Antigen Release Behavior Promote Immune Response
Open accessAbstract
In the quest to treat intracellular infectious diseases and virus infection, nanoparticles (NPs) have been considered to be efficient tools for inducing potent immune responses, specifically cellular immunity. Antigen processing and presenting by antigen presenting cells (APCs) could influence immune response, especially the priming of T-cell-mediated cellular immunity. Here, we fabricated pH-responsive poly(D,L-lactic-co-glycolic acid) (PLGA) NPs with rapid antigen intracellular release behavior in APCs. The NPs, which had thin shells and large inner space, contain ammonium bicarbonate (NH4HCO3), which could regulate release in endosomes and lysosomes, acting as an antigen release promoter in dendritic cells (DCs), and were coencapsulated with antigen (ovalbumin, OVA). Hydrogen ions (H(+)) in DC endosomes and lysosomes (pH ∼5.0 and 6.5) could react with NH4HCO3 to generate NH3 and CO2, which broke NPs and released antigens. After uptake by DCs, antigens encapsulated in pH-responsive PLGA NPs could escape from lysosomes into the cytoplasm and be cross-presented. Moreover, the NPs induced up-regulation of co-stimulatory molecules and stimulated cytokine production. Mouse immunization with pH-responsive PLGA NPs induced greater lymphocyte activation, more antigen-specific CD8(+) T cells, stronger cytotoxic capacity (IFN-γ and granzyme B), enhanced antigen-specific IgG antibodies, and higher serum IgG2a/IgG1, indicating cellular immunity. The NPs also improved generation of memory T cells to protect against reinfection. Thus, pH-responsive PLGA NPs, which induced strong cellular immune responses and offered antibody protection, could be potentially useful as effective vaccine delivery and adjuvant systems for the therapy of intracellular infectious diseases and virus infection.
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Liu et al. fabricated pH-responsive PLGA nanoparticles encapsulating NH4HCO3 to trigger antigen release from endo-lysosomes; NH4HCO3 interacted with protons, produced CO2 and NH3 to disrupt endo-lysosomes and promote antigen release into cytosol.
“Liu et al. fabricated pH-responsive poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating ammonium bicarbonate (NH4HCO3) to trigger antigen release from endo-lysosomes. NH4HCO3 interacted with protons in endo-lysosomes, then produced CO2 and NH3 to disrupt the endo-lysosomes and promote antigen release into the cytosol [183].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [183]
Cites
Immunobiology of Dendritic Cells
Banchereau, J., Brière, F., Caux, C., Davoust, J. M., Lebecque, S., Liu, Y., Pulendran, B., & Palucka, K. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.767 · Cited by 6,612 · see citing works
Antigen presentation and T cell stimulation by dendritic cells.
Guermonprez, P., Valladeau, J., Zitvogel, L., Théry, C., & Amigorena, S. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.100301.064828 · Cited by 2,106 · see citing works
Effector and memory T-cell differentiation: implications for vaccine development
Kaech, S. M., Wherry, E. J., & Ahmed, R. (2002) · Nature Reviews Immunology · doi:10.1038/nri778 · Cited by 1,865 · see citing works
Joshi, N. S., Cui, W., Chandele, A., Lee, H. K., Urso, D. R., Hagman, J., Gapin, L., & Kaech, S. M. (2007) · Immunity · doi:10.1016/j.immuni.2007.07.010 · Cited by 1,861 · see citing works
Segal, A. W. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115653 · Cited by 1,783 · see citing works
Cross-presentation by dendritic cells
Joffre, O. P., Segura, É., Savina, A., & Amigorena, S. (2012) · Nature reviews. Immunology · doi:10.1038/nri3254 · Cited by 1,646 · see citing works
CELL BIOLOGY OF ANTIGEN PROCESSING IN VITRO AND IN VIVO
Trombetta, E. S., & Mellman, I. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104538 · Cited by 1,173 · see citing works
Vaccine adjuvants: Current state and future trends
Petrovsky, N., & Aguilar, J. C. (2004) · Immunology and Cell Biology · doi:10.1111/j.0818-9641.2004.01272.x · Cited by 1,006 · see citing works
Savina, A., Jancic, C. C., Hugues, S., Guermonprez, P., Vargas, P., Moura, I. C., Lennon‐Duménil, A., Seabra, M. C., Raposo, G., & Amigorena, S. (2006) · Cell · doi:10.1016/j.cell.2006.05.035 · Cited by 896 · see citing works
Sensing and alarm function of resident memory CD8+ T cells
Schenkel, J., Fraser, K. A., Vezys, V., & Masopust, D. (2013) · Nature Immunology · doi:10.1038/ni.2568 · Cited by 648 · see citing works
From Vaccines to Memory and Back
Sallusto, F., Lanzavecchia, A., Araki, K., & Ahmed, R. (2010) · Immunity · doi:10.1016/j.immuni.2010.10.008 · Cited by 631 · see citing works
Aluminum compounds as vaccine adjuvants
Rk, G. (1998) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(98)00008-8 · Cited by 628 · see citing works
Kaech, S. M., & Wherry, E. J. (2007) · Immunity · doi:10.1016/j.immuni.2007.08.007 · Cited by 619 · see citing works
Kalia, V., Sarkar, S., Subramaniam, S., Haining, W. N., Smith, K. A., & Ahmed, R. (2010) · Immunity · doi:10.1016/j.immuni.2009.11.010 · Cited by 590 · see citing works
Nanotechnology in vaccine delivery
Peek, L. J., Middaugh, C. R., & Berkland, C. J. (2008) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.05.017 · Cited by 564 · see citing works
Adjuvants — a balance between toxicity and adjuvanticity
Rk, G., Relyveld, E. H., Lindblad, E. B., Bizzini, B., Ben‐Efraim, S., & Gupta, C. K. (1993) · Vaccine · doi:10.1016/0264-410x(93)90190-9 · Cited by 546 · see citing works
Wykes, M., Pombo, A., Jenkins, C., & MacPherson, G. G. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.3.1313 · Cited by 461 · see citing works
Brewer, J. M., Conacher, M., Hunter, C. A., Mohrs, M., Brombacher, F., & Alexander, J. K. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.12.6448 · Cited by 442 · see citing works
Karttunen, J. T., Sanderson, S., & Shastri, N. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.13.6020 · Cited by 420 · see citing works
Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination
Badovinac, V. P., Messingham, K. N., Jabbari, A., Haring, J. S., & Harty, J. T. (2005) · Nature Medicine · doi:10.1038/nm1257 · Cited by 403 · see citing works
Gherardi, R. K. (2001) · Brain · doi:10.1093/brain/124.9.1821 · Cited by 362 · see citing works
Adjuvant Properties of Aluminum and Calcium Compounds
Rk, G., Rost, B. E., Relyveld, E. H., & Siber, G. R. (1995) · Pharmaceutical biotechnology · doi:10.1007/978-1-4615-1823-5_8 · Cited by 334 · see citing works
Alum adjuvant: some of the tricks of the oldest adjuvant
Kool, M., Fierens, K., & Lambrecht, B. N. (2011) · Journal of Medical Microbiology · doi:10.1099/jmm.0.038943-0 · Cited by 321 · see citing works
Immunity in response to particulate antigen-delivery systems
Storni, T., Kündig, T. M., Senti, G., & Johansen, P. (2004) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2004.09.008 · Cited by 315 · see citing works
Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype
Demento, S. L., Cui, W., Criscione, J., Stern, E., Tulipan, J., Kaech, S., & Fahmy, T. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.03.041 · Cited by 287 · see citing works
Generation of effector CD8 + T cells and their conversion to memory T cells
Cui, W., & Kaech, S. M. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00926.x · Cited by 287 · see citing works
Cruz, L. J., Tacken, P. J., Fokkink, R., Joosten, B., Stuart, M. C., Albericio, F., Torensma, R., & Figdor, C. G. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.02.013 · Cited by 281 · see citing works
Polymeric Materials for Gene Delivery and DNA Vaccination
Nguyen, D. N., Green, J. J., Chan, J. M., Langer, R., & Anderson, D. G. (2008) · Advanced Materials · doi:10.1002/adma.200801478 · Cited by 273 · see citing works
Hirosue, S., Kourtis, I. C., van der Vlies, A. J., Hubbell, J. A., & Swartz, M. A. (2010) · Vaccine · doi:10.1016/j.vaccine.2010.09.077 · Cited by 234 · see citing works
Zhang, Z., Tongchusak, S., Mizukami, Y., Kang, Y., Ioji, T., Touma, M., Reinhold, B. B., Keskin, D. B., Reinherz, E. L., & Sasada, T. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.01.067 · Cited by 227 · see citing works
Proteolysis in MHC Class II Antigen Presentation
Villadangos, J. A., & Ploegh, H. L. (2000) · Immunity · doi:10.1016/s1074-7613(00)80176-4 · Cited by 185 · see citing works
Leleux, J. A., & Roy, K. (2012) · Advanced Healthcare Materials · doi:10.1002/adhm.201200268 · Cited by 184 · see citing works
Competitive adsorption of serum proteins at microparticles affects phagocytosis by dendritic cells
Thiele, L. (2003) · Biomaterials · doi:10.1016/s0142-9612(02)00525-2 · Cited by 151 · see citing works
Swartz, M. A., Hubbell, J. A., & Reddy, S. T. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2007.11.007 · Cited by 148 · see citing works
Polyanhydride microparticles enhance dendritic cell antigen presentation and activation
Torres, M. P., Wilson‐Welder, J. H., Lopac, S. K., et al. (2011) · Acta Biomaterialia · doi:10.1016/j.actbio.2011.03.023 · Cited by 124 · see citing works
Cui, W., Joshi, N. S., Jiang, A., & Kaech, S. M. (2009) · Vaccine · doi:10.1016/j.vaccine.2009.01.088 · Cited by 121 · see citing works
Activation of Antigen-Specific T Cell-Responses by Mannan-Decorated PLGA Nanoparticles
Hamdy, S. I., Haddadi, A., Shayeganpour, A., Samuel, J., & Lavasanifar, A. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0459-9 · Cited by 113 · see citing works
Chen, X., Liu, Y., Wang, L., Liu, Y., Zhang, W., Fan, B., Ma, X., Yuan, Q., Ma, G., & Su, Z. G. (2014) · Molecular Pharmaceutics · doi:10.1021/mp400597z · Cited by 103 · see citing works
Self-citationA two‐signal model for regulation of immunoglobulin isotype switching
Purkerson, J. M., & Isakson, P. C. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.14.1385241 · Cited by 93 · see citing works
The Cross‐priming Pathway: A Portrait of an Intricate Immune System
Basta, S., & Alatery, A. (2007) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2007.01909.x · Cited by 81 · see citing works
Wang, Y., Wu, J., Fan, Q., et al. (2013) · Advanced Healthcare Materials · doi:10.1002/adhm.201300335 · Cited by 49 · see citing works
Scott, C. J., Marouf, W. M., Quinn, D. J., Buick, R. J., Orr, S. J., Donnelly, R. F., & McCarron, P. A. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9400-7 · Cited by 43 · see citing works
Relationship between functional properties and structure of ovalbumin
Zemser, M., Friedman, M., Katzhendler, J., et al. (1994) · Journal of Protein Chemistry · doi:10.1007/bf01891984 · Cited by 39 · see citing works
Yue, H., Wei, W., Fan, B., et al. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2011.09.008 · Cited by 38 · see citing works
Tipping the Scales Toward More Effective Antibodies
Woof, J. M. (2005) · Science · doi:10.1126/science.1122009 · Cited by 31 · see citing works
Ruff, L. E., Mahmoud, E., Sankaranarayanan, J., Morachis, J. M., Katayama, C. D., Corr, M., Hedrick, S. Μ., & Almutairi, A. (2012) · Integrative Biology · doi:10.1039/c2ib20109g · Cited by 26 · see citing works
Mahmoud, A. A. F. (1995) · Infectious Disease Clinics of North America · doi:10.1016/s0891-5520(20)30658-9 · Cited by 3 · see citing works
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Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities
Li, L., Hu, S., & Chen, X. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.04.031 · Cited by 415 · see citing works
Self-citationLi, M., Zhao, M., Fu, Y., Li, Y., Gong, T., Zhang, Z., & Sun, X. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.02.043 · Cited by 201 · see citing works
Hu, J., Jiang, W., Yuan, L., Duan, C., Yuan, Q., Long, Z., Lou, X., & Xia, F. (2021) · Aggregate · doi:10.1002/agt2.10 · Cited by 172 · see citing works
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- Authors
- Liu, Q., Chen, X., Jia, J., Zhang, W., Yang, T., Wang, L., & Ma, G.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Wang, Lianyan
- Ma, Guanghui
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-04-24
- Volume
- 9
- Issue
- 5
- Pages
- 4925-4938
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W2025990308
- Cited by
- 233
- References
- 47
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 18 · 2023: 25 · 2022: 22 · 2021: 36 · 2020: 28 · 2019: 26 · 2018: 33 · 2017: 18 · 2016: 17 · 2015: 1
- FWCI
- 11.31
- Type
- journal article
- Language
- en
- Open access
- green
- ir.ipe.ac.cn
- Licence
- cc-by-nc-sa
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Institute of Process Engineering, CAS Institutional Repository (submittedVersion, cc-by-nc-sa)
- Funders
- Ministry of Science and Technology of the People's Republic of China (2012AA02A406, 2013CB531500)
- National Natural Science Foundation of China (21476243)
- Chinese Academy of Sciences (KSCX2-EW-R-19)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- pH-responsive nanoparticles, PLGA nanoparticles, antigen release, ammonium bicarbonate, dendritic cells, cross-presentation, cell-mediated immunity, ovalbumin, vaccine adjuvants, T cell immunity, memory T cells, intracellular infection, viral infection
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Adjuvants, Immunologic, Animals, Antigens, Dendritic Cells, Drug Carriers, Hydrogen-Ion Concentration, Immunity, Cellular, Lymphocyte Activation, Ovalbumin, Polyglycolic Acid, T-Lymphocytes, Time Factors, Vaccines, Antigen Presentation, Lactic Acid, Intracellular Space, Mice, Nanoparticles, Drug Liberation
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