Han Ling-Na, Wang Kai-Qiang, Ren Zi-Ning, Yang Xue, Duan Xiao, Krishnan Sasirekha, Jaisankar Abinaya, Park Jeong-Hui, Dashnyam Khandmaa, Zhang Wujie, Pedraz José Luis, Ramakrishna Seeram, Kim Hae-Won, Li Chang-Feng, Song Li-Hua, Ramalingam Murugan
Department of Pharmacy, Changzhi Medical College Changzhi 046000 Shanxi People's Republic of China
Department of Physiology, Changzhi Medical College Changzhi 046000 Shanxi People's Republic of China.
RSC Adv. 2022 Sep 30;12(43):27963-27969. doi: 10.1039/d2ra04436f. eCollection 2022 Sep 28.
In this study, we report a one-pot synthesis and enzyme-responsiveness of polyethylene glycol (PEG) and glutamic acid (Glu)-based amphiphilic doxorubicin (DOX) prodrug nanomicelles for cancer therapeutics. The nanomicelles were accomplished by esterification and amidation reactions. The nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) data confirmed the structure of nanomicelles. The DOX-loaded nanomicelles showed a DLS-measured average size of 107 nm and excellent stability in phosphate-buffered saline (PBS) for 7 days. The drug loading and cumulative release rates were measured by ultraviolet-visible (UV-vis) spectrophotometry at 481 nm. The cumulative release rate could reach 100% in an enzyme-rich environment. Further, the therapeutic efficiency of nanomicelles to cancer cells was determined by cell viability and cellular uptake and distribution using HeLa cells. The cell viability study showed that the DOX-loaded nanomicelles could effectively inhibit the HeLa cell proliferation. The cellular uptake study confirmed that the nanomicelles could be effectively ingested by HeLa cells and distributed into cell nuclei. Based on the collective experimental data, this study demonstrated that the synthesized nanomicellar prodrug of DOX is a potential candidate for cancer therapeutics.
在本研究中，我们报道了一种基于聚乙二醇（PEG）和谷氨酸（Glu）的两亲性阿霉素（DOX）前药纳米胶束的一锅法合成及其酶响应性，用于癌症治疗。纳米胶束通过酯化和酰胺化反应制备而成。核磁共振（NMR）和傅里叶变换红外光谱（FTIR）数据证实了纳米胶束的结构。载有DOX的纳米胶束经动态光散射（DLS）测量的平均粒径为107 nm，在磷酸盐缓冲盐水（PBS）中7天内具有优异的稳定性。通过紫外可见（UV-vis）分光光度法在481 nm处测量药物负载量和累积释放率。在富含酶的环境中，累积释放率可达100%。此外，利用HeLa细胞通过细胞活力、细胞摄取和分布来确定纳米胶束对癌细胞的治疗效果。细胞活力研究表明，载有DOX的纳米胶束能够有效抑制HeLa细胞增殖。细胞摄取研究证实，纳米胶束能够被HeLa细胞有效摄取并分布到细胞核中。基于这些综合实验数据，本研究表明合成的DOX纳米胶束前药是癌症治疗的潜在候选药物。
