A copper nanocluster-based multifunctional nanoplatform for augmented chemo/chemodynamic/photodynamic combination therapy of breast cancer. (January 2023)

• Record Type: Journal Article
• Authors: Zhang, Jie; Li, Pingfei; Wang, Tianyi; Li, Jiayang; Yun, Kaiqing; Zhang, Xiaoyan; Yang, Xinggang
• Is Part Of: Pharmacological research. Volume 187(2023)
• Publication Date: 2023-01
• Subjects: Copper clusters -- Fenton-like activity -- Glutathione depletion -- Tumor microenvironment response -- Multimodal theranostic strategy; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2022.106632
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: With the development of nano drug delivery system, the treatment mode that can overcome the shortcomings of chemotherapy drugs and integrate combined therapy remains to be explored. Herein, a nano drug system was designed to achieve the combined effect of chemo/chemodynamic/photodynamic therapy on cancer. Specifically, copper clusters (CuNCs) were used as the carrier, hyaluronic acid (HA) and doxorubicin (DOX) were coupled on CuNCs and then and chlorin e6 (Ce6) was introduced to form the self-assembled HA-CuNCs@DC nanoparticles. In this system, the HA-CuNCs@DC was involved in the reaction to the acidic tumor microenvironment (TME)-release of DOX, which could not only inhibit tumor growth through chemotherapy, but enhance the generation of hydrogen peroxide. CuNCs carriers had the properties of Fenton-like activity to realize chemodynamic therapy (CDT) and oxidase-like activity to deplete intracellular glutathione (GSH). Additionally, the chemotherapy drug susceptibility increased owing to the GSH depletion and the outbreak of reactive oxygen species, indicating the enhanced CDT efficacy and amplified chemotherapy efficacy. It was also noteworthy that Ce6 could be activated by 660 nm light to produce abundant singlet oxygen for photodynamic therapy. Overall, our platform demonstrated excellent biosafety and tumor suppression capabilities. This multimodal theranostic strategy provided new insights into cancer therapy. Graphical Abstract: ga1 Highlights: The prepared HA-CuNCs@DC samples were expected to have some advantages as follows. The HA-CuNCs@DC achieved the chemo/chemodynamic/photodynamic combination therapy. HA-CuNCs@DC self-supplied H2O2 and possess drug enhanced·OH generation capability. The CuNCs showed excellent oxidase-like activity and drug loading capability. The experimental results indicated that the combination of CuNCs, DOX, and Ce6 (Chemo/Chemodynamic/Photodynamic) will take on more efficient anti-tumor effect.