Mixed-charge pseudo-zwitterionic mesoporous silica nanoparticles with lowfouling and reduced cell uptake properties

TL;DR

This study develops mixed-charge pseudo-zwitterionic mesoporous silica nanoparticles that exhibit low-fouling and reduced cell uptake, enhancing drug delivery potential and antimicrobial efficacy for bacterial infection treatments.

Contribution

The paper introduces a novel pseudo-zwitterionic surface modification for MSNs that significantly reduces protein adhesion and macrophage uptake, improving biocompatibility and targeting in drug delivery.

Findings

70-90% reduction in serum protein adsorption

60% decrease in macrophage cellular uptake

Potential for effective bacterial infection treatment

Abstract

The design of drug delivery systems needs to consider biocompatibility and host body recognition for an adequate actuation. In this work, mesoporous silica nanoparticles (MSNs) surfaces were successfully modified with two silane molecules to provide mixed-charge brushes (-NH3/-PO3) and well evaluated in terms of surface properties, low-fouling capability and cell uptake in comparison to PEGylated MSNs. The modification process consists in the simultaneous direct-grafting of hydrolysable short chain amino (aminopropyl silanetriol, APST) and phosphonate-based (trihydroxy-silyl-propyl-methyl-phosphonate, THSPMP) silane molecules able to provide a pseudo-zwitterionic nature under physiological pH conditions. Results confirmed that both mixed-charged pseudo-zwitterionic MSNs (ZMSN) and PEG-MSN display a significant reduction of serum protein adhesion and macrophages uptake with respect to pristine MSNs. In the case of ZMSNs, his reduction is up to a 70-90% for protein adsorption and c.a. 60% for cellular uptake. This pseudo-zwitterionic modification has been focused on the aim of local treatment of bacterial infections through the synergistic effect between the capability of the nanocarriers to transport and deliver specific drugs and the electrostatic interactions between the mixed-charge systems and bacteria. These findings open promising future expectations for the effective treatment of bacterial infections through the use mixed-charge pseudo-zwitterionic MSNs furtive to macrophages and with antimicrobial properties.