Mixed-Valence Pt(0)/Pt2+ Nanoassemblies as High-Z Radiosensitizers and Metallo-Immune Regulators for Potent Radiotherapy of Breast Cancer

Abstract

Platinum (Pt)-based high-Z metallic nanoassemblies are admittedly effective radiosensitizers for radiotherapy. The preparation of metallic nanoassemblies with supramolecular self-assembly approach depends on the use of a metal-organic framework or coordination polymer (CP) as a template, which brings about challenges of removing template, controlling nanoassembly size and sufficiently loading Pt to obtain high catalytic efficiency essential for radiosensitizers. Herein, a novel synthetic strategy for fabricating metallic nanoassemblies was developed by introducing an imine group and reducing moiety into the metal-organic CPs, resulting in a reversible redox property. Owing to the nanoconfinement ability of this redox-labile CP template, a one-step synthetic pathway allows the formation of mixed-valence Pt nanoassemblies (PNAs) [Pt(0)/Pt 2+ ] that spontaneously encapsulate high-density and small-sized Pt nanoparticles in the CP template. The PNAs not only catalyze the hydrogen peroxide into oxygen but also release Pt ions in the tumor environment, thus simultaneously exhibits radiosensitization to improve the radiodynamic therapy and activates an antitumor immune response. Meanwhile, the PNAs bear the potential to act as a computed tomography-imaging agent for tumor diagnosis due to the high density of Pt loaded. Both in vitro and in vivo evaluations manifest the attractive properties of PNAs as a radiation-driven theranostic nanoplatform for tumor treatment.

Note:

Funding Information: This work was supported by National Natural Science Foundation of China (52073313, 51933011, 31971296), Guangdong Basic and Applied Basic Research Foundation (2020A1515110091), Science, Technology & Innovation Commission of Shenzhen Municipality (JCYJ20190807154013295), the Key Areas Research and Development Program of Guangzhou (202007020006), Guangdong Provincial Key Laboratory of Sensing Technology and Biomedical Instrument (Sun Yat-sen University, No.2020B1212060077).

Declaration of Interests: The authors declare no conflict of interest.

Ethics Approval Statement: Ethics approval was obtained by Ruiye model animal (Guangzhou) Biotechnology Co., LtdExperimental Animal Ethics Committee Inspection.

Keywords: Platinum nanoassemblies, coordination polymers, radiosensitizer, radiodynamic therapy, metallo-immune regulator, CT imaging