Receptor Ligand-Free Mesoporous Silica Nanoparticles: A Streamlined Strategy for Targeted Drug Delivery across the Blood-Brain Barrier

Zih An Chen, Cheng Hsun Wu, Si-Han Wu, Chiung Yin Huang, Chung Yuan Mou, Kuo Chen Wei, Yun Yen, I. Ting Chien, Sabiha Runa, Yi-Ping Chen, Peilin Chen

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Mesoporous silica nanoparticles (MSNs) represent a promising avenue for targeted brain tumor therapy. However, the blood-brain barrier (BBB) often presents a formidable obstacle to efficient drug delivery. This study introduces a ligand-free PEGylated MSN variant (RMSN25-PEG-TA) with a 25 nm size and a slight positive charge, which exhibits superior BBB penetration. Utilizing two-photon imaging, RMSN25-PEG-TA particles remained in circulation for over 24 h, indicating significant traversal beyond the cerebrovascular realm. Importantly, DOX@RMSN25-PEG-TA, our MSN loaded with doxorubicin (DOX), harnessed the enhanced permeability and retention (EPR) effect to achieve a 6-fold increase in brain accumulation compared to free DOX. In vivo evaluations confirmed the potent inhibition of orthotopic glioma growth by DOX@RMSN25-PEG-TA, extending survival rates in spontaneous brain tumor models by over 28% and offering an improved biosafety profile. Advanced LC-MS/MS investigations unveiled a distinctive protein corona surrounding RMSN25-PEG-TA, suggesting proteins such as apolipoprotein E and albumin could play pivotal roles in enabling its BBB penetration. Our results underscore the potential of ligand-free MSNs in treating brain tumors, which supports the development of future drug-nanoparticle design paradigms.

Original languageEnglish
Pages (from-to)12716-12736
Number of pages21
JournalACS Nano
Volume18
Issue number20
DOIs
Publication statusPublished - May 21 2024

Keywords

  • blood−brain barrier
  • brain tumor
  • doxorubicin
  • mesoporous silica nanoparticles
  • protein corona
  • the enhanced permeability and retention effect

ASJC Scopus subject areas

  • General Materials Science
  • General Engineering
  • General Physics and Astronomy

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