Self-activated arsenic manganite nanohybrids for visible and synergistic thermo/immuno-arsenotherapy.

Autor: Zhai Y; Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China., Liu M; Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China., Yang T; Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China., Luo J; Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China., Wei C; Department of Radiology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China. Electronic address: 20214133003@stu.suda.edu.cn., Shen J; Department of Radiology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China. Electronic address: shenjunkang@suda.edu.cn., Song X; Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China., Ke H; Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China., Sun P; Department of Otolaryngology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China., Guo M; Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China., Deng Y; Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. Electronic address: ybyi@suda.edu.cn., Chen H; Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China. Electronic address: chenhb@suda.edu.cn.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2022 Oct; Vol. 350, pp. 761-776. Date of Electronic Publication: 2022 Sep 08.
DOI: 10.1016/j.jconrel.2022.08.054
Abstrakt: Arsenotherapy has been clinically exploited to treat a few types of solid tumors despite of acute promyelocytic leukemia using arsenic trioxide (ATO), however, its efficacy is hampered by inadequate delivery of ATO into solid tumors owing to the absence of efficient and biodegradable vehicles. Precise spatiotemporal control of subcellular ATO delivery for potent arsenotherapy thus remains challengeable. Herein, we report the self-activated arsenic manganite nanohybrids for high-contrast magnetic resonance imaging (MRI) and arsenotherapeutic synergy on triple-negative breast cancer (TNBC). The nanohybrids, composed of arsenic‑manganese-co-biomineralized nanoparticles inside albumin nanocages (As/Mn-NHs), switch signal-silent background to high proton relaxivity, and simultaneously afford remarkable subcellular ATO level in acidic and glutathione environments, together with reduced ATO resistance against tumor cells. Then, the nanohybrids enable in vivo high-contrast T 1 -weighted MRI signals in various tumor models for delineating tumor boundary, and simultaneously yield efficient arsenotherapeutic efficacy through multiple apoptotic pathways for potently suppressing subcutaneous and orthotopic breast models. As/Mn-NHs exhibited the maximum tumor-to-normal tissue (T/N) contrast ratio of 205% and tumor growth inhibition rate of 88% at subcutaneous 4T1 tumors. These nanohybrids further yield preferable synergistic antitumor efficacy against both primary and metastatic breast tumors upon combination with concurrent thermotherapy. More importantly, As/Mn-NHs considerably induce immunogenic cell death (ICD) effect to activate the immunogenically "cold" tumor microenvironment into "hot" one, thus synergizing with immune checkpoint blockade to yield the strongest tumor inhibition and negligible metastatic foci in the lung. Our study offers the insight into clinically potential arsenotherapeutic nanomedicine for potent therapy against solid tumors.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
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