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J Control Release. 2018 Oct 28;288:34-44. doi: 10.1016/j.jconrel.2018.08.037. Epub 2018 Aug 29.

A tumor targeted near-infrared light-controlled nanocomposite to combat with multidrug resistance of cancer.

Author information

1
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.; Institute of Biomedical Research, Shandong University of Technology, Zibo 255000, PR China.
2
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
3
Department of Clinical Pharmacy, Hangzhou First People's Hospital, The Affiliated Hospital of Nanjing Medical University, Hangzhou 310006, PR China.
4
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.. Electronic address: lingds@zju.edu.cn.
5
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.. Electronic address: gaojianqing@zju.edu.cn.

Abstract

Stimuli-responsive nanomaterials have emerged as promising drug delivery systems for tumor therapy, as they can specifically respond to tumor-associated stimuli and release the loaded drugs in a controllable manner. However, most currently available stimuli-responsive nanomedicines rely on surrounding extreme stimulus to trigger the activity, which can be inefficient under dynamic and complex living conditions. Herein, we report a near-infrared (NIR) light-responsive nanocomposite, which can generate reactive oxygen species to efficiently trigger the decomposition upon NIR laser irradiation. This nanocomposite is fabricated by conjugating polyamidoamine-pluronic F68 and graphene oxide via diselenide bond, and encapsulating the NIR photosensitizer indocyanine green and chemotherapeutic drug doxorubicin (DOX) as payloads. Under NIR light, the nanocomposite shows lysosomal escape, controlled drug release, and nuclear trafficking of DOX inside multidrug resistant (MDR) MCF-7/ADR cells. Interestingly, this nanocomposite effectively down-regulates ABCB1 gene and P-glycoprotein of MCF-7/ADR cells, exhibiting significant cytotoxicity. In vivo anti-tumor study demonstrates an effective accumulation and superior therapeutic efficacy of this multifunctional nanocomposite in MCF-7/ADR tumors, representing a great potential for clinical treatment of MDR cancer.

KEYWORDS:

Diselenide bond; Graphene oxide; Indocyanine green; Multidrug resistance; Near-infrared light-responsive

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