Systematic Evaluation of Transferrin-Modified Porous Silicon Nanoparticles for Targeted Delivery of Doxorubicin to Glioblastoma

Meihua Luo, Guido Lewik, Julian Charles Ratcliffe, Chung Hang Jonathan Choi, Ermei Mäkilä, Wing Yin Tong, Nicolas H. Voelcker

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)33637−33649
Number of pages13
JournalACS Applied Materials and Interfaces
Volume11
Issue number37
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • blood-brain barrier
  • glioblastoma
  • porous silicon particles
  • targeted delivery
  • transferrin

Cite this

Luo, Meihua ; Lewik, Guido ; Ratcliffe, Julian Charles ; Choi, Chung Hang Jonathan ; Mäkilä, Ermei ; Tong, Wing Yin ; Voelcker, Nicolas H. / Systematic Evaluation of Transferrin-Modified Porous Silicon Nanoparticles for Targeted Delivery of Doxorubicin to Glioblastoma. In: ACS Applied Materials and Interfaces. 2019 ; Vol. 11, No. 37. pp. 33637−33649.
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Systematic Evaluation of Transferrin-Modified Porous Silicon Nanoparticles for Targeted Delivery of Doxorubicin to Glioblastoma. / Luo, Meihua; Lewik, Guido; Ratcliffe, Julian Charles; Choi, Chung Hang Jonathan; Mäkilä, Ermei; Tong, Wing Yin; Voelcker, Nicolas H.

In: ACS Applied Materials and Interfaces, Vol. 11, No. 37, 01.01.2019, p. 33637−33649.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Systematic Evaluation of Transferrin-Modified Porous Silicon Nanoparticles for Targeted Delivery of Doxorubicin to Glioblastoma

AU - Luo, Meihua

AU - Lewik, Guido

AU - Ratcliffe, Julian Charles

AU - Choi, Chung Hang Jonathan

AU - Mäkilä, Ermei

AU - Tong, Wing Yin

AU - Voelcker, Nicolas H.

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