Carrier‐Free H2O2 Self‐Supplier for Amplified Synergistic Tumor Therapy. Issue 7 (9th December 2022)

• Record Type: Journal Article
• Authors: Yang, Tianhao; Zhou, Man; Gao, Min; Qin, Weiji; Wang, Qian; Peng, Hui; Yao, Wanqing; Qiao, Lei; He, Xiaoyan
• Is Part Of: Small. Volume 19:Issue 7(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-09
• Subjects: carrier‐free -- chemodynamic therapies -- chemotherapies -- GSH depletion -- H 2O 2 self‐sufficiency -- photothermal therapies; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202205692
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Chemodynamic therapy (CDT) utilizes Fenton or Fenton‐like reactions to convert hydrogen peroxide (H2 O2 ) into cytotoxic hydroxyl radicals (OH) and draws extensive interest in tumor therapy. Nevertheless, high concentrations of glutathione (GSH) and insufficient endogenous H2 O2 often cause unsatisfactory therapeutic efficacy. Herein, a GSH‐depleting and H2 O2 self‐providing carrier‐free nanomedicine that can efficiently load indocyanine green (ICG), β‐lapachone (LAP), and copper ion (Cu 2+ ) (ICG‐Cu 2+ ‐LAP, LICN) to mediate synergetic photothermal and chemotherapy in enhanced chemodynamic therapy is designed. The results show that LICNs successfully enter tumors owing to the enhanced permeability and retention effect. Through the reductive intracellular environment, Cu 2+ in LICN can react with intracellular GSH, alleviate the antioxidant capacity of tumor tissues, and trigger the release of drugs. When LICN is subjected to near‐infrared (NIR) irradiation, enhanced photothermal effect and upregulated expression of NAD(P)H quinone oxidoreductase‐1 (NQO1) are observed. Meanwhile, the released LAP not only supports chemotherapy but also catalyzes NQO1 and produces sufficient endogenous H2 O2, thereby increasing the efficiency of Cu + ‐based Fenton‐like reaction. Notably, GSH depletion and H2 O2 self‐sufficiency generate sufficient OH and kill tumor cells with high specificity. Overall, the study provides an innovative strategy to self‐regulate GSH and H2 O2 levels for effective anticancer therapy. Abstract : A GSH‐depleting, H2 O2 self‐providing carrier‐free nanomedicine that can efficiently load the photosensitizer indocyanine green (ICG), chemotherapeutic drug β‐lapachone (LAP), and Cu 2+ (ICG‐Cu 2+ ‐LAP, LICN) to mediate synergetic photothermal and chemotherapy in enhanced chemodynamic therapy is discussed. The results show that LICNs can deplete GSH, supply H2 O2, and generate sufficient·OH to kill tumor cells with high specificity in vitro and in vivo.