Transferrin-Conjugated Red Blood Cell Membrane-Coated Poly(lactic-co-glycolic acid) Nanoparticles for the Delivery of Doxorubicin and Methylene Blue
Transferrin-Conjugated Red Blood Cell Membrane-Coated Poly(lactic-co-glycolic acid) Nanoparticles for the Delivery of Doxorubicin and Methylene Blue
复制标题
DOI：
10.1021/acsanm.0c00502
复制
发表时间：
2020-04-24
影响因子：
5.9
通讯作者：
Ghosh, Siddhartha Sankar
中科院分区：
文献类型：
--
作者：
Bidkar, Anil Parsram;Sanpui, Pallab;Ghosh, Siddhartha Sankar
在这里，我们展示了以转铁蛋白(Tf)受体为靶点的红细胞膜包裹纳米颗粒(NPs)的制备，以实现化疗和光动力效应。采用挤出法制备了多柔比星(Dox)和亚甲基蓝(MB)负载PLGA纳米粒，制备了Tf-DoxMB纳米粒。表征结果表明，所制备的纳米粒子为球形(106+/-23 nm)，Zeta电位为-12.6 mV。将转铁蛋白偶联膜包覆于纳米粒表面，可将药物定向输送至表达转铁蛋白受体的癌细胞。随后，用红色激光照射处理过的细胞，产生光敏剂MB中的活性氧。靶向递送Dox和MB，并在随后的激光照射下选择性地消灭癌细胞。活性分析和组合指数(CI)分析显示，化疗和光动力疗法具有协同作用。有趣的是，由于光敏化产生的Dox和ROS的抗增殖作用导致了DNA损伤介导的HeLa和MCF-7细胞的凋亡。由于Dox和MB的协同作用，Tf-DoxMB纳米粒在肿瘤球体中的靶向效率非常有趣。
Herein, we demonstrate the preparation of transferrin (TF) receptor-targeted RBC membrane coated nanoparticles (NPs) to achieve chemotherapeutic and photodynamic effects. The TF conjugated RBC membranes were developed to incorporate doxorubicin (Dox) and methylene blue (MB) loaded PLGA NPs by the extrusion method to produce TF-DoxMB NPs. Characterizations revealed that the NPs were spherical in size (106 +/- 23 nm) with a zeta potential (zeta) of -12.6 mV. Coating of the TF conjugated membrane on the NP surface resulted in targeted delivery of the drugs to the TF receptor expressing cancer cells. Following this, exposure of the treated cells with red laser generated reactive oxygen species from photosensitizer MB. Targeted delivery of Dox and MB with subsequent laser irradiation selectively annihilated cancer cells. Viability assays and combination index (CI) analysis revealed synergistic action of the chemo- and photodynamic therapy. Interestingly, the antiproliferative effect of Dox and ROS produced due to photosensitization led to DNA damage mediated apoptosis in HeLa and MCF-7 cells. Targeting efficiency of the TF-DoxMB NPs was quite intriguing in tumor spheroids due to the synergistic action of Dox and MB.