期刊
ACS NANO
卷 7, 期 3, 页码 2042-2055出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn304235j
关键词
vaccines; PLGA nanoparticles; dissolvable microneedles; immunotherapy; skin dendritic cells
类别
资金
- Department for Employment and Learning of Northern Ireland
- Wellcome Trust UK [WT008532]
- Biotechnology and Biological Sciences Research Council [BB/E020534/1] Funding Source: researchfish
- BBSRC [BB/E020534/1] Funding Source: UKRI
The efficacious delivery of antigens to antigen-presenting cells (APCs), In particular, to dendritic cells (DCs), and their subsequent activation remains a significant challenge in the development of effective vaccines. This study highlights the potential of dissolving microneedle (MN) arrays laden with nanoencapsulated antigen to increase vaccine immunogenicity by targeting antigen specifically to contiguous DC networks within the skin. Following in situ uptake, skin-resident DCs were able to deliver antigen-encapsulated poly-D,L-lactide-co-glycolide (PGLA) nanoparticles to cutaneous draining lymph nodes where they subsequently induced significant expansion of antigen-specific T cells. Moreover, we show that antigen-encapsulated nanoparticle vaccination via microneedles generated robust antigen-specific cellular immune responses In mice. This approach provided complete protection in vivo against both the development of antigen-expressing B16 melanoma tumors and a murine model of para-influenza, through the activation of antigen-specific cytotoxic CD8(+) T cells that resulted In efficient clearance of tumors and virus, respectively. In addition, we show promising findings that nanoencapsulation facilitates antigen retention into skin layers and provides antigen stability in microneedles. Therefore, the use of biodegradable polymeric nanoparticles for selective targeting of antigen to skin DC subsets through dissolvable MNs provides a promising technology for improved vaccination efficacy, compliance, and coverage.
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