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An extracellular pH-driven targeted multifunctional manganese arsenite delivery system for tumor imaging and therapy

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Abstract

Expanding the use of arsenic trioxide (ATO, As2O3) in cancer chemotherapy has received extensive attention in recent years owing to its remarkable efficacy in treating acute promyelocytic leukemia (APL). To date, the use of ATO for clinical treatment of solid tumors is still limited by its poor biocompatibility and severe toxic side effects. To address these limitations, here we developed a pH-low insertion peptide (pHLIP) modified ATO-based multifunctional drug-delivery system (DDS), which is termed MnAs@SiO2–pHLIP. With the coating of pHLIP, MnAs@SiO2–pHLIP could efficiently target the acidic tumor microenvironment, resulting in high intracellular accumulation of the DDS. As a “smart” nanoparticle (NP) platform, the DDS could controllably discharge the loaded ATO in response to acidic environments, which promotes the apoptosis of cancer cells. The features of controlled release capacity and the outstanding targeting ability contribute to better anticancer efficacy and less toxicity towards normal tissues compared with free ATO. It is worth noting that the acidic tumor microenvironment would also trigger the release of manganese ions (Mn2+) that brighten the T1 signal, which is exploited for real-time monitoring via contrast-enhanced magnetic resonance imaging (MRI). These multifunctional features, as demonstrated by both in vitro and in vivo experiments, could potentially expand the use of ATO to the treatment of solid tumors. We believe that MnAs@SiO2–pHLIP could serve as an auspicious agent for cancer theranostics and find tremendous applications in cancer management.

Graphical abstract: An extracellular pH-driven targeted multifunctional manganese arsenite delivery system for tumor imaging and therapy

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Publication details

The article was received on 11 Feb 2019, accepted on 25 Mar 2019 and first published on 26 Mar 2019


Article type: Paper
DOI: 10.1039/C9BM00216B
Biomater. Sci., 2019, Advance Article

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    An extracellular pH-driven targeted multifunctional manganese arsenite delivery system for tumor imaging and therapy

    K. Zhang, H. Lin, J. Mao, X. Luo, R. Wei, Z. Su, B. Zhou, D. Li, J. Gao and H. Shan, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C9BM00216B

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