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ACS Appl Mater Interfaces. 2018 Jan 31;10(4):4271-4284. doi: 10.1021/acsami.7b17506. Epub 2018 Jan 22.

Intelligent MoS2 Nanotheranostic for Targeted and Enzyme-/pH-/NIR-Responsive Drug Delivery To Overcome Cancer Chemotherapy Resistance Guided by PET Imaging.

Dong X1,2, Yin W1, Zhang X1, Zhu S1, He X1, Yu J1, Xie J1, Guo Z1, Yan L1, Liu X2, Wang Q3, Gu Z1,2, Zhao Y1,2,4.

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CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences , Beijing 100049, China.
College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences , Beijing 100049, China.
School of Material Science and Engineering, Institute of Nano Engineering, Shandong University of Science and Technology , Qingdao 266590, China.
CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Chinese Academy of Sciences , Beijing 100190, China.


Chemotherapy resistance remains a major hurdle for cancer therapy in clinic because of the poor cellular uptake and insufficient intracellular release of drugs. Herein, an intelligent, multifunctional MoS2 nanotheranostic (MoS2-PEI-HA) ingeniously decorated with biodegradable hyaluronic acid (HA) assisted by polyethyleneimine (PEI) is reported to combat drug-resistant breast cancer (MCF-7-ADR) after loading with the chemotherapy drug doxorubicin (DOX). HA can not only target CD44-overexpressing MCF-7-ADR but also be degraded by hyaluronidase (HAase) that is concentrated in the tumor microenvironment, thus accelerating DOX release. Furthermore, MoS2 with strong near-infrared (NIR) photothermal conversion ability can also promote the release of DOX in the acidic tumor environment at a mild 808 nm laser irradiation, achieving a superior antitumor activity based on the programmed response to HAase and NIR laser actuator. Most importantly, HA targeting combined with mild NIR laser stimuli, rather than using hyperthermia, can potently downregulate the expression of drug-resistance-related P-glycoprotein (P-gp), resulting in greatly enhanced intracellular drug accumulation, thus achieving drug resistance reversal. After labeled with 64Cu by a simple chelation strategy, MoS2 was employed for real-time positron emission tomography (PET) imaging of MCF-7-ADR tumor in vivo. This multifunctional nanoplatform paves a new avenue for PET imaging-guided spatial-temporal-controlled accurate therapy of drug-resistant cancer.


MoS2 nanosheets; controlled therapy; surface modification; targeting and P-gp inhibition; theranostics

[Indexed for MEDLINE]

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