Zwitterion‐Based Hydrogen Sulfide Nanomotors Induce Multiple Acidosis in Tumor Cells by Destroying Tumor Metabolic Symbiosis

Abstract

Destruction of tumor metabolism symbiosis is an attractive cancer treatment method which targets tumor cells with little harm to normal cells. Yet, a single intervention strategy and poor penetration of the drug in tumor tissue result in limited effect. Herein, we propose a zero‐waste zwitterion‐based hydrogen sulfide (H2S)‐driven nanomotor based on the basic principle of reaction in human body. When loaded with monocarboxylic acid transporter inhibitor α‐cyano‐4‐hydroxycinnamic acid (α‐CHCA), the nanomotor can move in tumor microenvironment and induce multiple acidosis of tumor cells and inhibit tumor growth through the synergistic effect of motion effect, driving force H2S and α‐CHCA. Given the good biosafety of the substrate and driving gas of this kind of nanomotor, as well as the limited variety of nanomotors currently available to move in the tumor microenvironment, this kind of nanomotor may provide a competitive candidate for the active drug delivery system of cancer treatment.

Intelligent polymeric hydrogen sulfide delivery systems for therapeutic applications

“…[ 147 ] could be utilized to regulate H 2 S delivery by modulating macromolecular architectures. A TME responsive zwitterionic H 2 S delivery system was recently reported by Wan et al, which was formed through the polymerization of zwitterionic sulfobetaine methacrylate monomer using N,N′ -bis-(acryloyl) cystamine as crosslinker and the subsequent loading of L-cysteine (L-Cys) and α-cyano-4-hydroxycinnamic acid (α-CHCA) [ 65 ]. It could be degraded by high concentration of GSH in TME to release L-Cys and α-CHCA.…”

Artificial nanomotors: Fabrication, locomotion characterization, motion manipulation, and biomedical applications

“…In another example shown in Figure 10D, Mao et al reported that the penetration distance of nanomotors was 150 μm which was longer than that of non‐nanomotors (50 μm), indicating the effective intracellular drug distribution by nanomotors. [ 113 ] They observed good performances of nanomotors by detecting the biological distribution, tumor enrichment effect, as well as the therapeutic effect in vivo. These prior in vivo studies have obviously cleared a path toward direct evaluation of disease‐oriented therapeutic efficacy associated with nanomotor‐enabled active drug delivery.…”

Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review)

“…Another strategy for cancer treatment is destroying the tumor metabolism symbiosis. This method successfully affects cancer cells with minimum impairment to healthy cells by using a zero-waste zwitterion-based H 2 S-driven nanomotor that generates acidosis in cancer cells within the TME, and consequently, the tumor growth will be suppressed ( 115 ).…”