Wissenschaft Aktuell

Kniep, R�diger; Jaenicke, Lothar; Winter, Roland; Fischer-Henningsen, Doris; Lippert, Bernhard; Gottschild, D.; Umbrecht, Hans; Zahn, Thomas

doi:10.1002/ciuz.19960300109

Cited by 1 publication

(1 citation statement)

References 23 publications

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“…To optimize the process further, the most efficient loading buffer was identified. To enable hydrophobic interaction between R848 and the phenyl moieties inside the pores, a buffer with antichaotropic or rather kosmotropic ions was chosen according to the Hofmeister series. − As can be seen in supplemental Figure S2, SSC20x buffer led to the best loading result of the phenyl-functionalized MSNs.…”

Section: Results and Discussionmentioning

confidence: 99%

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

et al. 2021

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Nanoparticle-based delivery systems for cancer immunotherapies aim to improve the safety and efficacy of these treatments through local delivery to specialized antigenpresenting 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 pHresponsive drug carrier system for the anticancer immunestimulant R848 (resiquimod), a synthetic Toll-like receptor 7 and 8 agonist. Equipped with a biotin−avidin cap, the tailormade 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.

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