A GSH-responsive drug delivery system based on self-assembly of polyoxometalates modified camptothecin for chemotherapy

Amphiphilic self-assembly bridges nanoscale engineering with biological functionality, forming compartmentalized nanocarriers that enable stimuli-responsive drug delivery. We engineered a glutathione (GSH)-responsive amphiphilic conjugate (POMs-SS-CPT) by covalently linking hydrophilic polyoxometalates (POMs) with hydrophobic drug camptothecin (CPT) through disulfide bonds, alongside a non-responsive carbon-bonded control (POMs-CC-CPT). Both compounds spontaneously self-assembled into vesicles in aqueous solution, enhancing cellular internalization. The GSH-responsive POMs-SS-CPT vesicles leveraged amphiphilic nanostructuring to achieve tumor-specific triggered co-release of POMs and CPT. This spatially controlled release minimized off-target toxicity while exerting potent synergistic antitumor activity. Both in vitro and in vivo studies demonstrated that POMs-SS-CPT vesicles exhibited superior antitumor efficacy and markedly inhibited tumor growth. This work establishes a novel GSH-responsive vesicular platform for efficient POM-based combination chemotherapy and elucidates critical design principles for redox-responsive delivery, providing a mechanistic framework for nanomedicine delivery systems.