Microfluidics assembled cRGD-functionalized liposomes co-delivering glucose oxidase and paclitaxel for αvβ3 integrin targeted melanoma therapy

Malignant melanoma is one of the most lethal and aggressive skin cancers, with treatment options often limited by its intrinsic resistance to conventional chemotherapy. Herein, we assembled cyclic arginine-glycine-aspartate(cRGD)-functionalized liposomes co-loaded with glucose oxidase (GOx) and paclitaxel (PTX) using a polydimethylsiloxane (PDMS) microfluidic chip. The optimized GOx/PTX@cRGD-Lipo system demonstrated monodisperse particle size distribution, high encapsulation efficiency (>80 % for both GOx and PTX), and sustain colloidal stability at 4°C. The cRGD modification enabled the selective targeting of α v β 3 -integrins overexpressed on melanoma cells. In vitro, GOx/PTX@cRGD-Lipo demonstrated enhanced cellular uptake, significantly reduced viability, and induced apoptosis, accompanied by cell cycle arrest in the G2/M and S phases of A375 melanoma cells. These effects were driven by the synergistic interplay of GOx-mediated starvation therapy, oxidative stress, and PTX chemotherapy, with GOx serving as a central therapeutic component. In a xenograft model, the liposomes exhibited potent tumor-targeting efficacy, achieving 68.75 % tumor growth inhibition without systemic toxicity. Our findings highlight that the dual drug-loaded, cRGD-functionalized liposomes could offer a feasible strategy for targeted melanoma therapy through combined tumor-specific delivery and multimodal synergy.