Chemodynamic therapy (CDT) has emerged as a promising strategy for cancer treatment. However, its effectiveness has been hindered by insufficient hydrogen peroxide (H 2 O 2 ) and high reductive glutathione (GSH) within tumors, which are the two main reasons for the inefficiency of Fenton/Fenton-like reaction-based CDT. Herein, we present a H 2 O 2 boost-GSH depletion strategy for enhanced CDT to fight against melanoma through a microneedle (MN)-based transcutaneous delivery method. The MN system is composed of dissolvable polyvinylpyrrolidone integrated with stimuli-responsive prodrugs. Under an intracellular acidic environment, the smart release of H 2 O 2 boosting components is triggered, subsequently initiating nitric oxide (NO) release and enhancing the Fenton-like reaction in a cascade manner. The generation of hydroxyl radicals ( • OH), along with the depletion of GSH by NO, amplifies the oxidative stress within tumor cells, promoting apoptosis and ferroptosis. The antitumor efficacy of the MN patch is validated in an A375 mouse melanoma model. This "H 2 O 2 boost-GSH depletion-Fenton killing" strategy expands the options for superficial tumor treatment through MN-mediated enhanced CDT.
Keyphrases
- hydrogen peroxide
- nitric oxide
- oxidative stress
- wastewater treatment
- nitric oxide synthase
- fluorescent probe
- randomized controlled trial
- room temperature
- cell death
- systematic review
- skin cancer
- stem cells
- metal organic framework
- endoplasmic reticulum stress
- drug delivery
- bone marrow
- cell proliferation
- ischemia reperfusion injury
- reactive oxygen species
- diabetic rats
- heat stress
- cell cycle arrest
- heat shock