Anti-angiogenesis therapy has offered an innovative strategy to fight gastric cancer (GC) in the clinic. However, the systemic acquired resistance, low drug specificity, as well as diffusional hindrance of agents to the tumor site severely limit this mono-therapeutic method. To overcome the obstacles, we design and prepare a parallel targeted nanoplatform (Src-I1/CR NPs), which is self-assembled by Src kinase inhibitor (Src-I1) and near-infrared (NIR) phototherapeutic agent (CR) to fight GC. Under laser irradiation, the Src-I1/CR NPs can induce localized cellular apoptosis with mitochondrial and lysosomal damage, triggering excellent GC hyperthermia-ablation. Simultaneously, the nano-conjugate blocks the Src/STAT3/VEGF pathway to activate the anti-angiogenesis effect for tumor starving by inhibiting the supply of nutrients and oxygen. More importantly, Src-I1/CR NPs also restrain the Src-mediated PI3K/AKT pathway to comprehensively suppress cancer cell proliferation, invasion, and migration. Overall, multimodal NIR Src-I1/CR NPs initiate precise parallel targeting cancer cells with serious mitochondrial and lysosomal dysfunction as well as desired cellular apoptosis for augmented photo-ablation, which offers a promising avenue in further GC preclinical investigation.
Wang et al. (Mon,) studied this question.