期刊
JOURNAL OF CONTROLLED RELEASE
卷 351, 期 -, 页码 970-988出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2022.10.002
关键词
cancer immunotherapy; PLGA nanoparticles; SIINFEKL; CpG ODN; Glycosylation
资金
- Ministry of Science and Technology, Taiwan [108-2320-B038-039-MY3, 110-2320-B-038-026]
- Jin-lung-yuan Foundation
In this study, glycosylated poly(lactic-co-glycolic acid) nanoparticles (NPs) loaded with tumor-specific antigens and adjuvants were developed for targeted delivery to dendritic cells (DCs). The results showed that the glycosylated NPs effectively enhanced antigen uptake and DC maturation, and promoted cellular immunity and T-cell recruitment into tumor sites in vivo.
Cancer vaccines have recently garnered tremendous interest. However, the targeted delivery of antigens and adjuvants to dendritic cells (DCs) still remains challenging. In this study, we developed glycosylated poly(lactic-co-glycolic acid) nanoparticles (NPs) loaded with the SIINFEKL peptide (OVA) as a tumor-specific antigen and CpG oligodeoxynucleotide (CpG) as an adjuvant for an effective DC-targeted cancer vaccine. Surface modification of NPs with galactose (Gal) or mannose (Man) was carried out by a double-emulsion solvent evaporation method, and the products were respectively named OVA-CpG Gal-NPs and OVA-CpG Man-NPs. They exhibited a uniform particle size, high loading capacity, robust stability, and extended release. The OVA-CpG Gal-NPs were found to rapidly enhance antigen uptake and DC maturation. In the in vivo study, OVA-CpG Gal-NPs via intravenous (i.v.), intranasal (i.n.) and subcutaneous (s.c.) routes had rapidly accumulated in the spleen. Moreover, the non-glycosylated OVA-CpG NPs after s.c. immunization could rapidly be trafficked to distal lymph nodes and sustained higher levels. All of these formulations increased the level of cluster of differentiation 4 -positive (CD4(+)) T cells and interferon (IFN)-gamma in the spleen, then promoted the cytotoxic CD8(+) tumor-infiltrating lymphocytes against E.G7-OVA lymphomas. In conclusion, galactosylated NPs provided an effective platform to enhance the DC targeting to induce cellular immunity and T-cell recruitment into tumor sites in vivo, thus showing great potential to be developed as a prophylactic vaccine for cancer immunotherapy.
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