Wu Mi, Yang Wenhua, Chen Sheng, Yao Jinrong, Shao Zhengzhong, Chen Xin
State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, China.
J Mater Chem B. 2018 Feb 28;6(8):1179-1186. doi: 10.1039/c7tb03113k. Epub 2018 Feb 7.
The continual generation of drug resistance is a major challenge in clinical cancer chemotherapy. Combination drug therapy may overcome such limitations by minimizing the required dosage of each drug whilst achieving an enhancement of therapeutic efficacy. Regenerated silk fibroin (RSF) is a commonly used drug delivery platform due to its suitable biocompatibility, controllable biodegradability, and diverse material formats. Herein, dual drug-loaded RSF nanospheres were prepared using a facile and green method to deliver two anti-cancer drugs with distinct physical properties, namely hydrophobic paclitaxel (PTX) and hydrophilic doxorubicin (DOX). The particle size of the PTX/DOX-loaded RSF nanospheres was easily regulated, by varying the RSF and ethanol concentrations during the formation process, from approximately 100 to 600 nm, with subsequent applications in both intravenous and lymphatic chemotherapy. The drug release profile of both PTX and DOX in the PTX/DOX-loaded RSF nanospheres was found to be well controlled and sustained for over 7 days. Further, the dual drug-loaded RSF nanospheres exhibited a high cellular uptake via endocytosis. Importantly, the dual drug-loaded RSF nanospheres showed more efficient suppression of cancer cell growth than the single drug-loaded RSF nanospheres with either drug or the free drugs at the same concentration, particularly at a DOX/PTX ratio of 1 : 1. Thus, the prepared dual drug nanocarrier with a controllable particle size may have important clinical implications for combination chemotherapy.
耐药性的不断产生是临床癌症化疗中的一项重大挑战。联合药物疗法可以通过最小化每种药物的所需剂量，同时提高治疗效果来克服这些局限性。再生丝素蛋白（RSF）因其合适的生物相容性、可控的生物降解性和多样的材料形式，是一种常用的药物递送平台。在此，采用简便绿色的方法制备了负载两种药物的RSF纳米球，用于递送两种具有不同物理性质的抗癌药物，即疏水性的紫杉醇（PTX）和亲水性的阿霉素（DOX）。通过在形成过程中改变RSF和乙醇浓度，负载PTX/DOX的RSF纳米球的粒径可轻松调控，范围约为100至600nm，随后可应用于静脉化疗和淋巴化疗。发现负载PTX/DOX的RSF纳米球中PTX和DOX的药物释放曲线均得到良好控制，并可持续7天以上。此外，负载两种药物的RSF纳米球通过内吞作用表现出较高的细胞摄取率。重要的是，与相同浓度下负载单一药物的RSF纳米球或游离药物相比，负载两种药物的RSF纳米球对癌细胞生长的抑制作用更有效，尤其是在DOX/PTX比例为1∶1时。因此，制备的粒径可控的双药纳米载体可能对联合化疗具有重要的临床意义。
