Co-delivery of Curcumin and Doxorubicin Using a pH-photothermal Dual-responsive and CD44-targeted Nanocarrier for Enhanced Chemo-photothermal Synergistic Tumor Treatment

In this study, we have developed a novel approach for synergistic tumor treatment by utilizing degradable dendritic mesoporous silica nanoparticles loaded with doxorubicin and curcumin (Cur). These nanoparticles are equipped with polydopamine (PDA) for photothermal therapy and hyaluronic acid (HA) as a targeting ligand. The incorporation of PDA not only ensures the controlled release of therapeutic agents but also confers pH and photothermal responsiveness to the nanocarriers. Cur, a natural compound, serves as an antitumor sensitizer, elevating intracellular ROS levels to promote apoptosis. In addition, the excellent biocompatibility and targeting property of nanocarriers were enhanced by the HA-modification, improving the effective accumulation in tumor cells. Comprehensive research including MTT assay, live/dead staining and ROS generation proved that the excellent antitumor capability of dual-drug loaded nanocarriers was a result of chemo-photothermal synergistic therapy and Cur-induced cellular amplified ROS generation. The cellular uptake assays further demonstrated the efficiency of HA-mediated intracellular accumulation, accelerated uptake driven by photothermal-induced and a precise internalization pathway of nanocarriers. Furthermore, the results of in vivo biocompatibility revealed no significant blood and organ toxicity associated to the prepared nanocarriers. Our findings underscore the substantial potential of the proposed dual-drug loaded nanocarriers for chemo-photothermal synergistic therapy, offering a safe and promising strategy for effective tumor treatment. In this work, a pH-photothermal responsive doxorubicin/curcumin-loaded degradable dendritic mesoporous silica nanoparticles (DNCPDH) was successfully fabricated, in which curcumin could amplified the intracellular ROS level for promotion of tumor killing capability as an antitumor sensitizer. In addition, the DNCPDH nanocarriers exhibited enhanced chemo-photothermal synergistic tumor treatment, efficient intracellular uptake and high cellular accumulation.+image