Photoactivated H₂ Nanogenerator for Enhanced Chemotherapy of Bladder Cancer

Abstract

Hydrogen gas can mitigate oxidative stress in many diseases and is regarded to be safe and free of side effects. Inspired by a metalloenzyme in a variety of microorganisms, here, we propose a photoactivated H 2 nanogenerator that comprises a fluorinated chitosan (FCS), a chemotherapeutic drug (gemcitabine, GEM), and a catalyst of H 2 production ([FeFe]TPP) that can form self-assembled [FeFe]TPP/GEM/ FCS nanoparticles (NPs). The [FeFe]TPP/GEM/FCS NPs exhibit excellent transmucosal and tumor cell penetration capacities after intravesical instillation into the bladder and can efficiently produce H 2 gas in situ upon 660 nm laser irradiation, which significantly enhances the efficacy of hydrogen chemotherapy of cancer in vitro and in vivo. Moreover, we discover that H 2 gas in hydrogen chemotherapy can inhibit mitochondrial function, hinder ATP synthesis, and cause a reduction of the P-gp efflux pump function, which finally attenuates P-gp protein drug transport capacity in cancer cells. This photoactivated H 2 evolution in situ to improve the therapeutic efficacy of chemotherapy of bladder cancer may present an effective hydrogen chemotherapy strategy for cancer treatment.

Fluorinated Chitosan Mediated Synthesis of Copper Selenide Nanoparticles with Enhanced Penetration for Second Near‐Infrared Photothermal Therapy of Bladder Cancer

“…FCS was synthesized by grafting the fluoroalkane chains to CS via amide coupling following our reported protocol. [23,24] CS was used to prepared Cu 2-x Se@CS (CC) NPs as non-fluorinated counterparts as the control. The morphologies and sizes of the as-prepared CC and CF NPs were examined by transmission electron microscopy (TEM).…”

“…[21] Our previous research has demonstrated that fluorinated cationic polymers including polyethylenimine and CS could form selfassembled nanoparticles with polypeptides, photosensitizers, or sonosensitizers for remarkably improving their transmucosal adsorption and tumor permeability in the bladder wall, which can further enhance the intravesical instillation therapy. [22][23][24] More specially, fluorinated CS (FCS) possesses high biocompatibility for intravesical instillation and could reversibly modulate the tight junctions of bladder epithelium for effectively transmucosal delivery of drugs. [23] Therefore, we reason that the binding with FCS would remarkably enhance the penetration of photothermal agents in the bladder to achieve potent PTT for BCa treatment.…”

Novel gas‐based nanomedicines for cancer therapy

“…have synthesized a photoactivated H 2 nanogenerator comprising [FeFe]‐hydrogenase, fluorinated chitosan (FCS), and gemcitabine (GEM). FCS was used to improve the transmembrane and transmucosal delivery of the nanogenerator 132 . Meanwhile, GEM together with [FeFe]TPP realizes controlled H 2 release within tumors under laser (660 nm) irradiation, thus significantly enhancing the efficacy of intravesical instillation chemotherapy.…”

“…(D) A photo‐activated H 2 nanogenerator capable of enhancing chemotherapy for bladder cancer. Reproduced with permission 132 . Copyright 2020, American Chemical Society.…”

Recent advances in upconversion nanoparticle-based nanocomposites for gas therapy

“…88 Since then, H 2 therapy has received much attention for the treatment of cancer and other inflammatory diseases. [89][90][91] The use of H 2 -rich water and saline has been tested in more than 50 clinical trials on several oxidative stressrelated/inflammatory diseases, including type II diabetes mellitus, stroke, Parkinson's disease, and cancer. [92][93][94] However, it is inconvenient to accurately control gas delivery to the diseased areas with macroscopic administration.…”