点击次数：

论文类型：期刊论文

发表时间：2019-01-01

发表刊物：ACTA BIOMATERIALIA

收录刊物：SCIE、PubMed

卷号：83

页面范围：359-371

ISSN号：1742-7061

关键字：Biodegradation; Versatility; Optional combination therapy; Layered double hydroxides; Manganese dioxide

摘要：A novel biodegradable versatile nanocarrier (FA-CM) was fabricated based on the self-assembly of delaminated CoAl-layered double hydroxides (LDHs) and manganese dioxide (MnO2) for optional combination cancer therapy. Biodegradation, versatility, targeting, bioimaging, in vitro cytotoxicity and in vivo antitumor efficacy were evaluated. The results showed that FA-CM could not only be effectively degraded into Co2+, Al3+ and Mn2+ to overcome the long-term toxic side effects, but also successfully load any positive charged, negative-charged, hydrophilic, and hydrophobic drug, meeting the critical requirement of versatile nanocarrier. Meanwhile, the presence of FA led to the higher uptake efficiency, cytotoxicity, and excellent fluorescence imaging of FA-CM toward cancerous cells. In particular, FA-CM exhibited glutathione and pH dual-response drug release, avoiding any premature leakage and side effects. The applicability of the FA-CM was determined by co-loading hydrophilic (doxorubicin (DOX)) and hydrophobic drug (paclitaxel (PTX)) for synergistic combination chemotherapy. In vitro cytotoxicity evaluation and a xenograft tumor model of hepatoma showed that this combination exhibited more efficient anticancer effects compared with either free drug alone or the corresponding cocktail solutions. Especially, the ratios of DOX and PTX loaded on FA-CM could be tuned as needed. A powerful approach is provided for the design and preparation of a biodegradable versatile nanocarrier with targeted ability and excellent biocompatibility, which can be potentially applied in clinical practice and medical imaging.
   Statement of Significance
   Drug delivery nanocarriers that can transport an effective dosage of drug molecules to targeted cells and tissues have been extensively designed to overcome the adverse side effects and low effectiveness of conventional chemotherapy. However, lack of biodegradability and versatility existing in majority of nanocarriers limit their further clinical applications. Thus, constructing a novel biodegradable versatile nanocarrier that can carry various types of drugs, is in urgent need and more suitable for commercial production and clinical use. In this study, we developed a novel biodegradable versatile nanocarrier (FA-CM) based on the self-assembly of delaminated CoAl-layered double hydroxides (LDHs) and manganese dioxide (MnO2) for optional combination cancer therapy. This work provides a new strategy for constructing versatile biodegradable platform for targeted drug delivery, which would have broad applications in cancer theranostics. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.