Systematic Evaluation of Transferrin-Modified Porous Silicon Nanoparticles for Targeted Delivery of Doxorubicin to Glioblastoma
| Autor: | Wing Yin Tong, Chung Hang Jonathan Choi, Nicolas H. Voelcker, Julian Ratcliffe, Guido Lewik, Ermei Mäkilä, Meihua Luo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Silicon
Materials science medicine.medical_treatment 02 engineering and technology Endocytosis Blood–brain barrier Targeted therapy 03 medical and health sciences Cell Line Tumor Glioma medicine Humans General Materials Science Doxorubicin Cytotoxicity 030304 developmental biology chemistry.chemical_classification Drug Carriers 0303 health sciences Transferrin 021001 nanoscience & nanotechnology medicine.disease medicine.anatomical_structure chemistry Delayed-Action Preparations Drug delivery Cancer research Nanoparticles Drug Screening Assays Antitumor Glioblastoma 0210 nano-technology Porosity medicine.drug |
| Zdroj: | ACS Applied Materials & Interfaces. 11:33637-33649 |
| ISSN: | 1944-8252 1944-8244 |
| DOI: | 10.1021/acsami.9b10787 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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