Feng Shini, Ren Yajing, Li Hui, Tang Yunfei, Yan Jinyu, Shen Zeyuan, Zhang Huijie, Chen Fuxue
School of Life Sciences, Shanghai University, Shanghai, 200444, People's Republic of China.
School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, People's Republic of China.
Int J Nanomedicine. 2021 Mar 11;16:2123-2136. doi: 10.2147/IJN.S266948. eCollection 2021.
Nanomaterial-based drug-delivery systems allowing for effective targeted delivery of smallmolecule chemodrugs to tumors have revolutionized cancer therapy. Recently, as novel nanomaterials with outstanding physicochemical properties, boron nitride nanospheres (BNs) have emerged as a promising candidate for drug delivery. However, poor dispersity and lack of tumor targeting severely limit further applications. In this study, cancer cell-membrane biomimetic BNs were designed for targeted anticancer drug delivery.
Cell membrane extracted from HeLa cells (HM) was used to encapsulate BNs by physical extrusion. Doxorubicin (Dox) was loaded onto HM-BNs as a model drug.
The cell-membrane coating endowed the BNs with excellent dispersibility and cytocompatibility. The drug-release profile showed that the Dox@HM-BNs responded to acid pH, resulting in rapid Dox release. Enhanced cellular uptake of Dox@HM-BNs by HeLa cells was revealed because of the homologous targeting of cancer-cell membranes. CCK8 and live/dead assays showed that Dox@HM-BNs had stronger cytotoxicity against HeLa cells, due to self-selective cellular uptake. Finally, antitumor investigation using the HeLa tumor model demonstrated that Dox@HM-BNs possessed much more efficient tumor inhibition than free Dox or Dox@BNs.
These findings indicate that the newly developed HM-BNs are promising as an efficient tumor-selective drug-delivery vehicle for tumor therapy.
基于纳米材料的药物递送系统能够实现小分子化学药物向肿瘤的有效靶向递送，彻底改变了癌症治疗方式。近来，作为具有卓越理化性质的新型纳米材料，氮化硼纳米球（BNs）已成为一种很有前景的药物递送候选材料。然而，其较差的分散性和缺乏肿瘤靶向性严重限制了其进一步应用。在本研究中，设计了癌细胞膜仿生氮化硼纳米球用于靶向抗癌药物递送。
从人宫颈癌细胞（HeLa）中提取的细胞膜（HM）通过物理挤压法用于包裹氮化硼纳米球。将阿霉素（Dox）作为模型药物负载到细胞膜包裹的氮化硼纳米球上。
细胞膜包被赋予了氮化硼纳米球优异的分散性和细胞相容性。药物释放曲线表明阿霉素负载的细胞膜包裹氮化硼纳米球（Dox@HM-BNs）对酸性pH有响应，导致阿霉素快速释放。由于癌细胞膜的同源靶向性，HeLa细胞对Dox@HM-BNs的细胞摄取增强。CCK8和活/死检测表明，由于自选择性细胞摄取，Dox@HM-BNs对HeLa细胞具有更强的细胞毒性。最后，使用HeLa肿瘤模型进行的抗肿瘤研究表明，Dox@HM-BNs比游离阿霉素或阿霉素负载的氮化硼纳米球（Dox@BNs）具有更高效的肿瘤抑制作用。
这些发现表明，新开发的细胞膜包裹氮化硼纳米球作为一种高效的肿瘤选择性药物递送载体用于肿瘤治疗具有广阔前景。
