Multifunctional platinum(IV) nanomicelle composites for chemo-photodynamic therapy and anti-metastasis in cancer treatment

Abstract

Cancer treatment continues to pose significant challenges, necessitating innovative strategies to address limitations such as drug resistance and toxicity. In this study, we present the design of Pt-ATRA-TPP@TPGS nanomicelle as multifunctional composites that integrate platinum-based chemotherapeutic agent with a photosensitizer and the anti-tumor metastasis drug ARTA, thereby facilitating a multifunctional therapeutic approach. In vitro experiments utilizing A549 and A549R cell models demonstrate high cellular uptake, effective generation of reactive oxygen species (ROS) upon activation by red light, and substantial cytotoxicity, particularly against drug-resistant cells. Furthermore, the nanomicelle exhibits superior anti-migratory efficacy in inhibiting B16F10 cell migration. In vivo studies conducted in mouse models reveal enhanced tumor regression and reduced lung metastasis, underscoring the effectiveness of the nanomicelle against both primary tumor and metastatic spread. The safety profile is favorable, exhibiting minimal toxicity compared to conventional platinum-based drugs. The underlying mechanism involves ligand-mediated targeting coupled with ROS-induced cellular damage. Overall, we have successfully developed novel Pt(IV)-based composites that synergistically combine chemotherapy, photodynamic therapy, and anti-metastatic effects to enhance cancer treatment outcomes.