Hierarchical nanoclusters with programmed disassembly for mitochondria-targeted tumor therapy with MR imaging

Abstract

Mitochondria are crucial metabolic organelles involved in tumorigenesis and tumor progression, and the induction of abnormal mitochondria metabolism is recognized as a strategy with strong potential for the exploration of advanced tumor therapeutics. Herein, hierarchical manganese silicate nanoclusters modified with triphenylphosphonium (MSNAs-TPP) were designed and synthesized for mitochondria-targeted tumor theranostics. The as-prepared MSNAs-TPP retains considerable dimensional and structural stability in the neutral physiological environment, favoring its accumulation at the tumor site. More interestingly, MSNAs-TPP may disassemble in a responsive manner to an acidic tumor microenvironment into ultrasmall manganese silicate nanocapsules (∼6 nm), enabling deep tumor penetration and mitochondria targeting. When reaching the mitochondria, the nanocapsules effectively deplete mitochondrial glutathione (GSH), and simultaneously release catalytic Mn2+ ions to induce amplified oxidative stress in the structure with the enriched CO2 and H2O2 from mitochondria metabolism. As a result, MSNAs-TPP presents considerable antitumor effect without a clear side effect, both in vitro and in vivo. The study may provide an alternative concept in the development of intelligent nanotherapeutics for tumor treatment with high efficacy.

Graphical abstract: Hierarchical nanoclusters with programmed disassembly for mitochondria-targeted tumor therapy with MR imaging

Supplementary files

Article information

Article type
Paper
Submitted
11 Sep 2021
Accepted
13 Oct 2021
First published
15 Oct 2021

Biomater. Sci., 2021, Advance Article

Hierarchical nanoclusters with programmed disassembly for mitochondria-targeted tumor therapy with MR imaging

C. Xie, D. Cen, H. Wang, Y. Wang, Y. Wu, G. Han and X. Li, Biomater. Sci., 2021, Advance Article , DOI: 10.1039/D1BM01423D

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