Light-Responsive conjugated polymer nanoparticles with Spatial-Controlled camptothecin release via π − π stacking for improved Combinatorial therapy of breast cancer
Zhaokui Zeng, Jingjing Tian, Wenjie Xu, Hailu Liu, Daxiong Xiang, Dehua Liao, Junyong Wu, Chuanpin Chen
Abstract
cRGD-PTer N25/CPT NPs is a new tool for Spatial/Temporal-Controlled drug release via π − π Stacking in tumor sites, and it is also a promising candidate for controllable and accurate combination tumor therapy. The tumor growth inhibition rate of the cRGD-PTer N25/CPT NPs group reached 93.6%. • A novel nano-system combining light-responsive photothermal therapy (PTT) with photothermal-responsive chemotherapy via π − π Stacking. • The cRGD-PTer N25/CPT NPs are designed for targeted PTT/chemotherapy, offering strong near-infrared absorption, 57.4% photothermal efficiency, and laser-triggered drug release. • This work presents a viable strategy for designing novel controlled-release drug systems to improve breast cancer treatment efficiency. The treatment of breast cancer (BC) remains a significant challenge, exemplified by the limitations of chemotherapy due to its high side effects. Light-responsive drug delivery systems (DDS) offer a promising approach to spatially and temporally release drugs, minimizing chemotherapy side effects and enhancing efficacy. However, achieving precise delivery and site-specific drug release poses complex challenges. Here, We present a novel nano-system combining light-responsive photothermal therapy (PTT) with photothermal-responsive chemotherapy via π − π Stacking. Conjugated polymer nanoparticles (cRGD-PTer N25/CPT NPs) is designed for spatiotemporal targeted PTT/chemotherapy. Research shows that the strong near-infrared absorption of PTer N25 endows cRGD-PTer N25/CPT NPs with excellent photothermal capabilities(57.4 %) and near-infrared laser-triggered drug release performance. The cRGD-PTer N25/CPT NPs enhanced BC-specific cellular accumulation, prolonged blood circulation, exhibited good biocompatibility, and improved PTT and chemotherapy efficacy in BC cell lines and mouse models while reducing systemic toxicity. The photothermal effect triggered the on-demand release of camptothecin (CPT), producing therapeutic effects and downregulating heat shock protein 70 (HSP 70), reducing cancer cell thermoresistance, and enhancing combined treatment efficacy. Under spatial and temporal control, the tumor growth inhibition rate of the cRGD-PTer N25/CPT NPs group reached 93.6 %, nearly eradicating tumor presence, whereas the control group exhibited only partial inhibition. Minimal cardiotoxicity and metastatic side effects are not observed. This work presents a viable strategy for designing novel controlled-release drug systems to improve breast cancer treatment efficiency.