Biodegradable, Hydrogen Peroxide, and Glutathione Dual Responsive Nanoparticles for Potential Programmable Paclitaxel Release

Abstract

Reactive oxygen species (ROS) and glutathione (GSH) dual responsive nanoparticulate drug delivery systems (nano-DDSs) hold great promise to improve the therapeutic efficacy and alleviate the side effects of chemo drugs in cancer theranosis. Herein, hydrogen peroxide (HO) and GSH dual responsive thioketal nanoparticle (TKN) was rationally designed for paclitaxel (PTX) delivery. Compared to other stimuli-sensitive nano-DDSs, this dual responsive DDS is not only sensitive to biologically relevant HO and GSH for on-demand drug release but also biodegradable into biocompatible byproducts after fulfilling its delivering task. Considering the heterogeneous redox potential gradient, the PTX loaded TKNs (PTX-TKNs) might first respond to the extracellular ROS and then to the intracellular GSH, achieving a programmable release of PTX at the tumor site. The selective toxicity of PTX-TKNs to tumor cells with high levels of ROS and GSH was verified both in vitro and in vivo.

Versatile Hyperbranched Poly(β-hydrazide ester) Macromers as Injectable Antioxidative Hydrogels

“…9 Li-Jun Wan et al reported a disulfide containing nanoparticle system for dual responsive to hydrogen peroxide and GSH, which showed a programmable paclitaxel release. 10 Therefore, a biocompatible material containing disulfide moieties would hold great promise to improve the antioxidative therapeutic efficacy.…”

A novel GSH responsive poly(alpha-lipoic acid) nanocarrier bonding with the honokiol-DMXAA conjugate for combination therapy

“…Considering that both cytotoxic drugs and VDAs need to reach the tumor site to produce a marked effect, we can use the tumor-microenvironment-responsive nanocarriers to enhance the selective release of cytotoxic drugs and VDAs at the tumor sites. According to the characteristics of tumor microenvironment, such as enzymes [12] and pH [13][14][15] differences, high reactive oxygen species (ROS) [16][17][18] and L-glutathione (GSH) [19] level, various stimuli-responsive nanocarriers have been designed. Of these aspects, as the GSH concentration of the malignant tissues is at least four-fold higher than that of the normal tissues [20][21][22], and the intracellular concentration of GSH is much higher than that in most extracellular fluids [23,24], many new GSH responsive nanoparticles achieved selective release of drugs at tumors [25].…”

Strategies To Design and Synthesize Polymer‐Based Stimuli‐Responsive Drug‐Delivery Nanosystems

“…It is well known that the extracellular ROS concentration is higher than that of the cytoplasm, but the intracellular GSH concentration is higher than that of the extracellular matrix. Based on this feature, Wan and co‐workers developed dual ROS‐/GSH‐responsive polymeric NPs (PTX‐TKNs; PTX: paclitaxel, TKN: thioketal nanoparticle) for programmable PTX release (Scheme D) . The TKNs were prepared from biocompatible dihydrolipoic acid (DHLA) and 2,2‐dimethoxypropane (DMP; Figure A).…”