Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, China.
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Acta Biomater. 2019 Jan 1;83:359-371. doi: 10.1016/j.actbio.2018.11.009. Epub 2018 Nov 7.
A novel biodegradable versatile nanocarrier (FA-CM) was fabricated based on the self-assembly of delaminated CoAl-layered double hydroxides (LDHs) and manganese dioxide (MnO) 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 Co, Al and Mn 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 (MnO) 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.
一种新型可生物降解的多功能纳米载体（FA-CM）是基于剥离的 CoAl 层状双氢氧化物（LDHs）和二氧化锰（MnO）的自组装构建的，用于可选的联合癌症治疗。评估了生物降解性、多功能性、靶向性、生物成像、体外细胞毒性和体内抗肿瘤疗效。结果表明，FA-CM 不仅可以有效地降解为 Co、Al 和 Mn，以克服长期的毒性副作用，而且还可以成功地装载任何带正电荷、带负电荷、亲水性和疏水性药物，满足多功能纳米载体的关键要求。同时，FA 的存在导致 FA-CM 对癌细胞的摄取效率更高、细胞毒性更强、荧光成像效果更好。特别是，FA-CM 表现出谷胱甘肽和 pH 双重响应的药物释放，避免了任何过早的泄漏和副作用。通过共装载亲水性（阿霉素（DOX））和疏水性药物（紫杉醇（PTX））进行协同组合化疗，确定了 FA-CM 的适用性。体外细胞毒性评价和肝癌异种移植肿瘤模型表明，与游离药物或相应的鸡尾酒溶液相比，这种组合表现出更有效的抗癌效果。特别是，FA-CM 上加载的 DOX 和 PTX 的比例可以根据需要进行调整。为设计和制备具有靶向能力和优异生物相容性的可生物降解的多功能纳米载体提供了一种强大的方法，该载体可潜在地应用于临床实践和医学成像。
设计和制备能够将有效剂量的药物分子输送到靶向细胞和组织的药物输送纳米载体已被广泛研究，以克服传统化疗的不良反应和低疗效。然而，大多数纳米载体中缺乏生物降解性和多功能性限制了它们的进一步临床应用。因此，构建一种新型的可生物降解的多功能纳米载体，能够携带各种类型的药物，是非常迫切的，更适合商业生产和临床使用。在本研究中，我们基于剥离的 CoAl 层状双氢氧化物（LDHs）和二氧化锰（MnO）的自组装，开发了一种新型的可生物降解的多功能纳米载体（FA-CM），用于可选的联合癌症治疗。这项工作为构建用于靶向药物输送的多功能可生物降解平台提供了一种新策略，该策略在癌症治疗学中有广泛的应用。
