pH/Redox/Lysozyme-Sensitive Hybrid Nanocarriers With Transformable Size for Multistage Drug Delivery

Abstract

The majority of current nanocarriers in cancer treatment fail to deliver encapsulated cargos to their final targets at therapeutic levels, which decreases the ultimate efficacy. In this work, a novel core–shell nanocarrier with a biodegradable property was synthesized for efficient drug release and subcellular organelle delivery. Initially, silver nanoparticles (AgNPs) were grafted with terminal double bonds originating from N, N′-bisacrylamide cystamine (BAC). Then, the outer coatings consisting of chitosan (CTS) and polyvinyl alcohol (PVA) were deposited on the surface of modified AgNPs using an emulsion method. To improve the stability, disulfide-containing BAC was simultaneously reintroduced to cross-link CTS. The as-prepared nanoparticles (CAB) possessed the desired colloidal stability and exhibited a high drug loading efficiency of cationic anticancer agent doxorubicin (DOX). Furthermore, CAB was tailored to transform their size into ultrasmall nanovehicles responding to weak acidity, high glutathione (GSH) levels, and overexpressed enzymes. The process of transformation was accompanied by sufficient DOX release from CAB. Due to the triple sensitivity, CAB enabled DOX to accumulate in the nucleus, leading to a great effect against malignant cells. In vivo assays demonstrated CAB loading DOX held excellent biosafety and superior antitumor capacity. Incorporating all the benefits, this proposed nanoplatform may provide valuable strategies for efficient drug delivery.

Advances in the variations and biomedical applications of stimuli-responsive nanodrug delivery systems

“…After being incubated in PBS (pH 5.0) with GSH (5 mM) and lysozyme (5 μg ml −1 ), the size of the nanoparticles decreased from approximately 175 nm to 10-20 nm. CAB@DOX with this size variable feature facilitates nuclear delivery of DOX [89].…”

Natural Biopolymers as Smart Coating Materials of Mesoporous Silica Nanoparticles for Drug Delivery

“…Enzymatic catalytic activity was indicated as another possible trigger for chitosan-coated smart DDS [ 191 ]. The release of doxorubicin was enhanced, incubating chitosan-coated hollow MSNs with colon enzymes [ 141 ].…”