Cell Type Determines the Light-Induced Endosomal Escape Kinetics of Multifunctional Mesoporous Silica Nanoparticles

Abstract

We investigated uptake and individual endosome lysis events in fibroblast, normal, and carcinoma cell lines using a colloidal mesoporous silica (CMS) nanoparticle (NP)-based reporter system with a covalently attached photosensitizer. Endosome lysis was induced through the activation of protoporphyrin IX (PpIX). Surprisingly, this release-on-demand system resulted in more broadly distributed lysis times than expected, particularly for Renca, a renal carcinoma cell line. An analysis of the NP load per endosome, endosome size, and uptake characteristics indicate that Renca cells not only take up a lower amount of NPs in comparison with the fibroblast cells but also have larger endosomes and a lower NP load per endosome. We then created a stochastic model detailing steps downstream of uptake to understand how much factors that cannot be directly measured, such as variations in the PpIX load per NP, affect the lysis time distributions. Model results indicate that the distributions are primarily determined by the endosome properties, rather than variations across NPs.

Intracellular chromobody delivery by mesoporous silica nanoparticles for antigen targeting and visualization in real time

“…For example, positively charged nanoparticles are favored for cellular uptake because the negatively charged cell membrane tends to attract the positively charged particles on its surface; particle sizes below 200 nm are considered the most favorable size for cellular internalization. In addition, the endocytosis behavior for different nanoparticles is also dependent on cell-type 29 30 . In this study, the MSN size used for intracellular chromobody delivery is about 100–200 nm.…”

The Red Color of Life Transformed – Synthetic Advances and Emerging Applications of Protoporphyrin IX in Chemical Biology

“…Alternative strategies for PPIX peptide couplings involve DMT‐MM‐mediated activation of the carboxylic acid moieties,[65g] conversion of the acids to mixed carboxylic anhydrides by the action of ethyl chloroformate and transformation of the ester groups of (protoporphyrinato dimethyl ester)cobalt(II) to acyl azides using hydrazine and nitrous acid. [72a]…”

Recent advances in porous nanoparticles for drug delivery in antitumoral applications: inorganic nanoparticles and nanoscale metal-organic frameworks

“…[19] The group of Thomas Bein has widely studied the attachment of photosensitizers (as protoporphyrin IX) on MSN surface in order to induce endosomal escape of these carriers when exposed to radiation at 405 nm. [20] Nearly all the nanocarriers that are internalized by mammalian cells are uptaken via endocytosis. Therefore, to achieve rapid escape from the endosomes is of paramount importance for intracellular drug delivery in order to avoid the degradation of the transported molecules within late endosomes or lysosomes.…”