Dendronized Mesoporous Silica Nanoparticles Provide an Internal Endosomal Escape Mechanism for Successful Cytosolic Drug Release

TL;DR

This paper introduces dendronized mesoporous silica nanoparticles that enable efficient cytosolic drug delivery by facilitating endosomal escape through their high buffering capacity, combining targeted delivery, stimuli-responsive release, and low toxicity.

Contribution

The study presents a novel dendron-functionalized MSN platform that combines high drug loading, targeted delivery, stimuli-responsive release, and an internal endosomal escape mechanism.

Findings

High drug loading capacity of dendronized MSNs

Effective endosomal escape via buffering capacity

Low cytotoxicity and targeted cancer cell uptake

Abstract

Mesoporous silica nanoparticles (MSNs) attract increasing interest in the field of gene and drug delivery due to their versatile features as a multifunctional drug delivery platform. Here, we describe poly(amidoamine) (PAMAM) dendron-functionalized MSNs that fulfill key prerequisites for a controllable intracellular drug release. In addition to high loading capacity, they offer 1) low cytotoxicity, showing no impact on the metabolism of endothelial cells, 2) specific cancer cell targeting due to receptor-mediated cell uptake, 3) a redox-driven cleavage of disulfide bridges allowing for stimuli-responsive cargo release, and most importantly, 4) a specific internal trigger based on the high buffering capacity of PAMAM dendrons to provide endosomal escape.