NIR-triggered and Thermoresponsive Core-shell nanoparticles for synergistic anticancer therapy

• Published in: Journal of controlled release 2024-10, Vol.374, p.194-204
• Main Authors: Zhang, Hong, Wang, Xiao, Yang, Xiaorong, Wu, Zehua, Chen, Qin, Wei, Qiaolin, Guo, Yong, Hu, Quan, Shen, Jia-Wei
• Format: Article
• Language: English
• Subjects: Chemotherapy; Drug delivery; Mesoporous silica; Photothermal therapy; Thermoresponsive; Tumor
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2024.08.014

Recent advancements in cancer treatment have underscored the inadequacy of conventional monotherapies in addressing complex malignant tumors. Consequently, there is a growing interest in synergistic therapies capable of overcoming the limitations of monotherapies, leading to more personalized and effective approaches. Among these, the combination of photothermal therapy (PTT) and chemotherapy has emerged as a promising avenue for tumor management. In this study, we present a novel approach utilizing thermoresponsive mesoporous silica nanoparticles (MSN) as a delivery system for the chemotherapeutic drug doxorubicin. By incorporating photothermal agent copper sulfide (CuS) nanoparticles into the MSN, the resulting composite material exhibits potent photothermal properties. Furthermore, the integration of an upper critical solution temperature (UCST) polymer within the silica outer layer serves as a “gatekeeper”, enabling precise control over drug release kinetics. This innovative nanomaterial effectively merges thermoresponsive behavior with PTT, thereby minimizing the collateral damage associated with traditional chemotherapy on healthy tissues. Moreover, in both in vitro studies using mouse breast carcinoma cells (4 T1) and in vivo experiments utilizing a 4 T1 tumor-bearing mouse model, our nanomaterials demonstrated synergistic effects, enhancing the anti-tumor efficacy of combined PTT and chemotherapy. With its remarkable photothermal conversion efficiency, robust stability, and biocompatibility, the UCST-responsive nanoplatform holds immense potential for clinical applications. Upon exposure to NIR laser irradiation, CuS nanoparticles induce photothermal conversion, elevating the temperature to the UCST and triggering the phase transition of the external polymer from hydrophobic to hydrophilic states. This controlled response facilitates the release of Dox from the pores of MSN. The resulting nanocarrier, featuring a synergistic combination of PTT and chemotherapy, demonstrated exceptional anti-tumor efficacy at both cellular and animal levels. [Display omitted] •A cascade response mechanism utilizing photothermal and temperature-responsive nanoplatform has been achieved.•The outer layer of UCST-type polymer on C@M@P acts as a “gatekeeper” to enable precise control over drug release kinetics.•Upon NIR laser irradiation, CuS induce photothermal conversion, triggering the phase transition of the external polymer.