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Title

Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice

Authors
Gößl, Dorothée
Ustyanovska, Natasha
Xiong, Mengyao
Hauser, Daniel
Zhuzhgova, Olga
Taskoparan, Betul
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Published in ACS Nano. 2021
Abstract Nanoparticle-based delivery systems for cancer immunotherapies aim to improve the safety and efficacy of these treatments through local delivery to specialized antigen-presenting cells (APCs). Multifunctional mesoporous silica nanoparticles (MSNs), with their large surface areas, their tunable particle and pore sizes and their spatially controlled functionalization, represent a safe and versatile carrier system. In this study, we demonstrate the potential of MSNs as a pH-responsive drug carrier system for the anticancer immune-stimulant R848 (resiquimod), a synthetic Toll-like receptor 7 and 8 agonist. Equipped with a biotin-avidin-cap, the tailor-made nanoparticles showed efficient stimuli-responsive release of their R848 cargo in an environmental pH of 5.5 or below. We showed that the MSNs loaded with R848 were rapidly taken up by APCs into the acidic environment of the lysosome and that they potently activated the immune cells. Upon subcutaneous injection into mice, the particles accumulated in migratory dendritic cells (DCs) in the draining lymph nodes, where they strongly enhanced the activation of the DCs. Furthermore, simultaneous delivery of the model antigen OVA and the adjuvant R848 by MSNs resulted in an augmented antigen-specific T-cell response. The MSNs significantly improved the pharmacokinetic profile of R848 in mice, as the half-life of the drug was increased 6-fold, and at the same time, the systemic exposure was reduced. In summary, we demonstrate that MSNs represent a promising tool for targeted delivery of the immune-modulator R848 to APCs and hold considerable potential as a carrier for cancer vaccines.
Keywords Mesoporous silica nanoparticlesDrug deliveryImmunotherapyStimuli-responsive capping systemToll-like receptor 7 agonistDendritic cell activationNanovaccine
Identifiers
PMID: 33648336
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Article (Published version) (5 MB) - public document Free access
Appendix (2 MB) - public document Free access
Other version: https://pubs.acs.org/doi/10.1021/acsnano.0c08384
Structures
Research groups Immunopharmacologie du cancer
Pharmaco-omiques et médecine de précision (1003)
Projects
Swiss National Science Foundation: 156372
Swiss National Science Foundation: 182317
Citation
(ISO format)
WAGNER, Julia et al. Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice. In: ACS Nano, 2021. doi: 10.1021/acsnano.0c08384 https://archive-ouverte.unige.ch/unige:150115

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Deposited on : 2021-03-05

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