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

Article Article scientifique Article Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice eng 2021 author Wagner Julia 857712 author Gößl Dorothée author Ustyanovska Natasha author Xiong Mengyao author Hauser Daniel author Zhuzhgova Olga author Hocevar Sandra 864752 author Taskoparan Betul 0000-0003-1890-1547 868268 Betul Taskoparan Yaglikci author Poller Laura author Datz Stefan author Engelke Hanna author Daali Youssef 46042 author Bein Thomas author Bourquin Carole 0000-0003-3862-4583 854541 10.1021/acsnano.0c08384 33648336 1936-086X https://pubs.acs.org/doi/10.1021/acsnano.0c08384 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. Mesoporous silica nanoparticles Drug delivery Immunotherapy Stimuli-responsive capping system Toll-like receptor 7 agonist Dendritic cell activation Nanovaccine Dewey 615 Dewey 617 Swiss National Science Foundation 156372 CH Swiss National Science Foundation 182317 CH 31 Section des sciences pharmaceutiques 17 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 false 1278 Immunopharmacologie du cancer 1280 Pharmaco-omiques et médecine de précision 1003 ACS Nano 47e76411-71fc-4d3a-8853-7d5e2a310053 Article (Published version) Public acsnano.0c08384.pdf 5255374 application/pdf CC BY-NC-ND 3ec148a7-3cb0-4e8d-8360-3329c3de66e4 Appendix Public nn0c08384_si_001.pdf 2129655 application/pdf CC BY-NC-ND openAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences

Title	Published in	Year	Views	Downloads

Role of Intratumoral HMGB1 in the Antitumor Immune Response		2022	737	167
Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice	ACS Nano	2021	394	525

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Taskoparan Yaglikci, Betul

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