Oxygen plasma-defect engineered WS2 nanosheets for combination therapy: Folate-targeted, photothermal, and electroporation-enhanced chemotherapy

We report the synthesis of a multifunctional drug delivery nanoplatform based on oxygen plasma-treated WS 2 (tungsten disulfide) nanosheets functionalized with folic acid-conjugated polyethylene glycol (PEG-FA). The [WS 2 ] OPT -PEG-FA nanosheets achieve an exceptionally high doxorubicin (DOX) loading of ∼316 % by weight due to the increased negative surface charge and defect states introduced by oxygen plasma treatment, far surpassing previous TMDC nanocarriers. They exhibit excellent stability and strong photothermal conversion under near-infrared (NIR) laser exposure. Drug release studies show pH- and laser-responsive behavior, with minimal DOX release at physiological pH 7.4 and significantly enhanced release under acidic conditions and NIR exposure. Folate functionalization mediates targeted uptake by cancer cells via folate receptor-mediated endocytosis, while electroporation with pulsed electric fields further increases intracellular delivery by transiently permeabilizing cell membranes. Importantly, both photothermal heating and electroporation elevated intracellular reactive oxygen species (ROS) levels, amplifying oxidative stress in cancer cells. In vitro combination therapy using [WS 2 ] OPT -PEG-FA/DOX with NIR photothermal treatment and electroporation yielded synergistic cytotoxicity, resulting in markedly enhanced cancer cell killing compared to individual treatments, while sparing normal cells. This work demonstrates a potent multi-modal cancer therapy platform, highlighting the critical role of oxygen plasma surface engineering in achieving superior drug loading, ROS-mediated stress, and therapeutic efficacy. • Oxygen plasma treatment enhances drug loading on WS 2 nanosheet surfaces. • Folate targeting improves cancer cell uptake of drug-loaded nanoplatforms. • Photothermal heating triggers controlled drug release inside tumor cells. • Electroporation boosts intracellular delivery through temporary pores. • Combined therapy shows strong cancer cell killing with minimal side effects.