转铁蛋白受体靶向的 PEG-PLA 聚合物胶束用于多形性胶质母细胞瘤的化疗。
Transferrin Receptor-Targeted PEG-PLA Polymeric Micelles for Chemotherapy Against Glioblastoma Multiforme.
机构信息
Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Immunology, Shenzhen University School of Medicine, Shenzhen 518060, People's Republic of China.
Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen 518060, People's Republic of China.
出版信息
Int J Nanomedicine. 2020 Sep 11;15:6673-6688. doi: 10.2147/IJN.S257459. eCollection 2020.
BACKGROUND
The safe and efficient delivery of chemotherapeutic agents is critical to glioma therapy. However, chemotherapy for glioma is extremely challenging because the blood-brain barrier (BBB) rigorously prevents drugs from reaching the tumor region.
MATERIALS AND METHODS
TfR-T12 peptide-modified PEG-PLA polymer was synthesized to deliver paclitaxel (PTX) for glioma therapy. TfR was significantly expressed on brain capillary endothelial cells and glioma cells; therefore, TfR-T12 peptide-modified micelles can cross the BBB system and target glioma cells.
RESULTS
TfR-T12-PEG-PLA/PTX polymeric micelles (TfR-T12-PMs) could be absorbed rapidly by tumor cells, and traversed effectively the BBB monolayers. TfR-T12-PMs can effectively inhibit the proliferation of U87MG cells in vitro, and TfR-T12-PMs loaded with paclitaxel presented better antiglioma effect with prolonged median survival of nude mice-bearing glioma than the unmodified PMs.
CONCLUSION
The TfR-T12-PMs could effectively overcome the BBB barrier and accomplish glioma-targeted drug delivery, thus validating its potential in improving the therapeutic outcome in multiforme.
背景
化疗药物的安全有效递送对神经胶质瘤的治疗至关重要。然而，由于血脑屏障（BBB）严格阻止药物到达肿瘤区域，因此针对神经胶质瘤的化疗极具挑战性。
材料与方法
合成转铁蛋白受体（TfR）-T12 肽修饰的聚乙二醇-聚乳酸（PEG-PLA）聚合物以递送紫杉醇（PTX）用于神经胶质瘤治疗。TfR 在脑毛细血管内皮细胞和神经胶质瘤细胞上均有显著表达；因此，TfR-T12 肽修饰的胶束可以穿过 BBB 系统并靶向神经胶质瘤细胞。
结果
TfR-T12-PEG-PLA/PTX 聚合物胶束（TfR-T12-PMs）可被肿瘤细胞迅速吸收，并有效地穿过 BBB 单层。TfR-T12-PMs 可以有效地抑制 U87MG 细胞在体外的增殖，并且负载紫杉醇的 TfR-T12-PMs 比未修饰的 PMs 具有更长的裸鼠荷瘤中位生存时间，表现出更好的抗神经胶质瘤作用。
结论
TfR-T12-PMs 可以有效地克服 BBB 屏障并实现神经胶质瘤靶向药物递送，从而验证了其在改善多形性胶质母细胞瘤治疗效果方面的潜力。
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