Tumor Microenvironment‐Responsive Cu/CaCO3‐Based Nanoregulator for Mitochondrial Homeostasis Disruption‐Enhanced Chemodynamic/Sonodynamic Therapy. Issue 38 (23rd August 2022)

• Record Type: Journal Article
• Authors: Zhao, Yajie; Bian, Yulong; Xiao, Xiao; Liu, Bin; Ding, Binbin; Cheng, Ziyong; Ma, Ping'an; Lin, Jun
• Is Part Of: Small. Volume 18:Issue 38(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-23
• Subjects: CaCO 3 biominerals -- calcium overload -- mitochondrial disruption -- synergistic therapy -- tumor microenvironment‐responsive (TME‐responsive); Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202204047
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: The efficiency of reactive oxygen species (ROS)‐mediated cancer therapy is restrained by intrinsic characteristics in the tumor microenvironment (TME), such as overexpressed glutathione (GSH), hypoxia and limited efficiency of H2 O2 . In this work, intelligent copper‐dropped calcium carbonate loading sonosensitizer Ce6 nanoparticles (Cu/CaCO3 @Ce6, CCC NPs) are established to realize TME‐responsive self‐supply of oxygen and successively Ca 2+ ‐overloading‐strengthened chemodynamic therapy/sonodynamic therapy (CDT/SDT). CCC NPs release Ca 2+, Cu 2+, and Ce6 in weakly acid and GSH‐excessive TME. Released Cu 2+ can not only consume GSH and turn into Cu + via a redox reaction, but also provide CDT‐creating hydroxyl radicals through the Fenton‐like reaction. Under ultrasound irradiation, the intracellular oxidative stress is amplified profoundly relying on singlet oxygen outburst from SDT. Moreover, Ca 2+ influx aggravates the mitochondrial disruption, which further accelerates the oxidation level. The facile and feasible design of the Cu‐dropped CaCO3 ‐based nanoregulators will be further developed as a paradigm in ROS‐contributed cancer therapy. Abstract : Cu/CaCO3 @Ce6 nanoparticles (CCC NPs) with almost spherical morphology are constructed by directly doping Cu 2+ during the facile one‐pot synthetic process of CaCO3 and loading sonosensitizer Ce6. Through tumor microenvironment‐response, the CCC NPs present US/H2 O2 ‐activated reactive oxygen species production, pH/glutathione‐sensitized double ions (Ca 2+ /Cu 2+ ) release, and Ca 2+ ‐overloading‐enhanced multimodal synergistic therapy than only for cargo delivery.