期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 14, 期 3, 页码 713-723出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2017.12.017
关键词
Redox-response nanomicelles; Active tumor targeting; Hyaluronic acid; Tocopherol succinate; Synergistic effect
资金
- National Natural Science Foundation of China [81501579, 81673364]
- Natural Science Foundation of Jiangsu Province [BK20150702]
- Ministry of Science and Technology of the People's Republic of China [2017ZX09101001]
- Chinese Pharmacopeia Commission [ZG2017-5-01]
- Six Talents Summit Program of Jiangsu Province
- Fundamental Research Funds for the Central Universities [2632018ZD13]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
Nanotechnology-based chemotherapy is efficient in cancer treatment due to the targeted delivery of small molecules via nano-carriers, which are usually regarded as inert. However, nano-materials are more preferred as carriers since many cause synergistic anti-tumor effects along with the drug cargo. In this study, a bioactive tocopherol succinate (TOS) was grafted to hyaluronic acid (HA) via of disulfide bonds to obtain HA-ss-TOS conjugates which can assemble into nano-micelles but dissociate when exposed to reducing environments in vitro and in vivo. Moreover, paclitaxel-loaded HA-ss-TOS micelles (HA-ss-TOS-PTX) can be efficiently taken up by B16F10 cells overexpressing CD 44, thereafter exhibiting enhanced cytotoxicity. The in vivo imaging study here revealed much greater tumor accumulation of Dir-labeled HA-ss-TOS compared to the free Dir group. In vivo antitumor activities further ensured that the PTX-loaded HA-ss-TOS micelles provided superior antineoplastic responses versus PTX-loaded HA-TOS micelles and Taxol. Moreover, the subcellular dissociated TOS from HA-ss-TOS showed synergistic effects with PTX. These experimental results revealed that reduction-responsive PTX-loaded polymeric nanomicelles with multi-functional properties hold great potential for anti-tumor treatment and, thus, should be further studied. (c) 2018 Elsevier Inc. All rights reserved.
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