Carrier-free nano-integrated strategy of phototherapy and chemotherapy for synergetic AKT targeted therapy to inhibit cancer metastasis and recurrence.

A key challenge in clinical anticancer treatments is metastasis and recurrence, to address this challenge, it is crucial to develop combination treatment strategies that target different molecular pathways, considering the high complexity of tumors, as well as to create efficient drug delivery systems that enhance therapeutic efficacy and minimize systemic toxicity. Herein, two clinical small molecular drugs indocyanine green (ICG) and paclitaxel (PTX) were self-assembled into relatively stable, carrier-free nanoparticles (IP NPs) through a simple one-step nanoprecipitation method. The spherical IP NPs demonstrate excellent aqueous stability, tumor-targeted accumulation, and potent apoptosis induction. Combined with AKT inhibitor MK-2206, they effectively modulate survival pathways, suppress metastasis, and prevent tumor recurrence in rechallenge models. This synergistic approach achieves equivalent therapeutic efficacy at reduced doses, enhancing treatment safety. Encouraged by its effective therapy and sensitivity-enhancing properties, this study might show significant potential for malignant tumor synergistic therapy.