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Published on: June 13, 2014
Self-assembled nanoplatform for synergistic anti-angiogenic/photothermal therapy against gastric cancer with
Lingling Wang1,2, Yi Zheng2, Kun Ye2
1School of Life Sciences, Anhui Medical University, Hefei, 230032, China.
Abstract:
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.
Insights
This study introduces a novel nanoplatform for gastric cancer (GC) therapy. The nanoparticle combines a Src kinase inhibitor and phototherapeutic agent to induce targeted cell death and inhibit tumor growth.
Area of Science:
- Oncology
- Nanomedicine
- Biotechnology
Background:
- Anti-angiogenesis therapy shows promise for gastric cancer (GC) but faces challenges like resistance and poor drug delivery.
- Current limitations hinder the effectiveness of single-agent therapies for GC.
Purpose of the Study:
- To develop a parallel targeted nanoplatform (Src-I1/CR NPs) to overcome limitations in GC treatment.
- To enhance anti-angiogenesis effects and induce targeted cancer cell death.
Main Methods:
- Self-assembly of Src kinase inhibitor (Src-I1) and a near-infrared (NIR) phototherapeutic agent (CR) into nanoparticles (NPs).
- Utilizing NIR laser irradiation to trigger localized cellular apoptosis and hyperthermia-ablation.
- Investigating the inhibition of key signaling pathways (Src/STAT3/VEGF and Src-mediated PI3K/AKT) by the nanoplatform.
Main Results:
- Src-I1/CR NPs induced localized apoptosis via mitochondrial and lysosomal damage under laser irradiation, leading to effective GC hyperthermia-ablation.
- The nanoplatform effectively blocked the Src/STAT3/VEGF pathway, activating anti-angiogenesis and starving tumors.
- Comprehensive suppression of cancer cell proliferation, invasion, and migration was observed through inhibition of the Src-mediated PI3K/AKT pathway.
Conclusions:
- Multimodal NIR Src-I1/CR NPs offer precise parallel targeting of gastric cancer cells.
- The nanoplatform induces mitochondrial and lysosomal dysfunction, leading to apoptosis and enhanced photo-ablation.
- This approach presents a promising strategy for preclinical investigation in gastric cancer treatment.
