A tumor targeted near-infrared light-controlled nanocomposite to combat with multidrug resistance of cancer

Abstract

Stimuli-responsive nanomaterials have emerged as promising drug delivery systems for tumor therapy, as they can specifically respond to tumor-associated stimuli and release the loaded drugs in a controllable manner. However, most currently available stimuli-responsive nanomedicines rely on surrounding extreme stimulus to trigger the activity, which can be inefficient under dynamic and complex living conditions. Herein, we report a near-infrared (NIR) light-responsive nanocomposite, which can generate reactive oxygen species to efficiently trigger the decomposition upon NIR laser irradiation. This nanocomposite is fabricated by conjugating polyamidoamine-pluronic F68 and graphene oxide via diselenide bond, and encapsulating the NIR photosensitizer indocyanine green and chemotherapeutic drug doxorubicin (DOX) as payloads. Under NIR light, the nanocomposite shows lysosomal escape, controlled drug release, and nuclear trafficking of DOX inside multidrug resistant (MDR) MCF-7/ADR cells. Interestingly, this nanocomposite effectively down-regulates ABCB1 gene and P-glycoprotein of MCF-7/ADR cells, exhibiting significant cytotoxicity. In vivo anti-tumor study demonstrates an effective accumulation and superior therapeutic efficacy of this multifunctional nanocomposite in MCF-7/ADR tumors, representing a great potential for clinical treatment of MDR cancer.