Systematic Evaluation of Transferrin-Modified Porous Silicon Nanoparticles for Targeted Delivery of Doxorubicin to Glioblastoma
Publication in refereed journal

香港中文大學研究人員
替代計量分析
.

其它資訊
摘要There is a dire need to develop more effective therapeutics to combat brain cancer such as glioblastoma multiforme (GBM). An ideal treatment is expected to target deliver chemotherapeutics to glioma cells across the blood-brain barrier (BBB). The overexpression of transferrin (Tf) receptor (TfR) on the BBB and the GBM cell surfaces but not on the surrounding cells renders TfR a promising target. While porous silicon nanoparticles (pSiNPs) have been intensely studied as a delivery vehicle due to their high biocompatibility, degradability, and drug-loading capacity, the potential to target deliver drugs with transferrin (Tf)-functionalized pSiNPs remains unaddressed. Here, we developed and systematically evaluated Tf-functionalized pSiNPs (Tf@pSiNPs) as a glioma-targeted drug delivery system. These nanoparticles showed excellent colloidal stability and had a low toxicity profile. As compared with nontargeted pSiNPs, Tf@pSiNPs were selective to BBB-forming cells and GBM cells and were efficiently internalized through clathrin receptor-mediated endocytosis. The anticancer drug doxorubicin (Dox) was effectively loaded (8.8 wt %) and released from Tf@pSiNPs in a pH-responsive manner over 24 h. Furthermore, the results demonstrate that Dox delivered by Tf@pSiNPs induced significantly enhanced cytotoxicity to GBM cells across an in vitro BBB monolayer compared with free Dox. Overall, Tf@pSiNPs offer a potential toolbox for enabling targeted therapy to treat GBM.
出版社接受日期22.08.2019
著者Meihua Luo, Guido Lewik, Julian Charles Ratcliffe, Chung Hang Jonathan Choi, Ermei Mäkilä, Wing Yin Tong, Nicolas H. Voelcker
期刊名稱ACS Applied Materials and Interfaces
出版年份2019
月份9
日期18
卷號11
期次37
出版社American Chemical Society
頁次33637 - 33649
國際標準期刊號1944-8244
語言美式英語

上次更新時間 2021-10-05 於 23:58