Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice
نویسندگان
چکیده
Nanoparticle-based delivery systems for cancer immunotherapies aim to improve the safety and efficacy of these treatments through local specialized antigen-presenting cells (APCs). Multifunctional mesoporous silica nanoparticles (MSNs), with their large surface areas, tunable particle pore sizes, spatially controlled functionalization, represent a safe versatile carrier system. In this study, we demonstrate potential MSNs as pH-responsive drug system anticancer immune-stimulant R848 (resiquimod), synthetic Toll-like receptor 7 8 agonist. Equipped biotin–avidin cap, tailor-made showed efficient stimuli-responsive release cargo in an environmental pH 5.5 or below. We that loaded were rapidly taken up by APCs into acidic environment lysosome they potently activated immune cells. Upon subcutaneous injection mice, particles accumulated migratory dendritic (DCs) draining lymph nodes, where strongly enhanced activation DCs. Furthermore, simultaneous model antigen OVA adjuvant resulted augmented antigen-specific T-cell response. The significantly improved pharmacokinetic profile half-life was increased 6-fold, at same time, systemic exposure reduced. summary, promising tool targeted modulator hold considerable vaccines.
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1Department of Chemistry, Nanosystems Initiative Munich (NIM) and Center for Nano Science (CeNS), University of Munich (LMU), Butenandtstr. 11 (E), 81377 Munich, Germany 2Department of Pharmacy, Pharmaceutical Biotechnology, Nanosystems Initiative Munich (NIM) and Center for Nano Science (CeNS), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany # authors contributed equally ...
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ژورنال
عنوان ژورنال: ACS Nano
سال: 2021
ISSN: ['1936-0851', '1936-086X']
DOI: https://doi.org/10.1021/acsnano.0c08384