Receptor Ligand-Free Mesoporous Silica Nanoparticles: A Streamlined Strategy for Targeted Drug Delivery across the Blood–Brain Barrier
Journal
ACS Nano
Journal Volume
18
Journal Issue
20
Start Page
12716
End Page
12736
ISSN
1936-0851
1936-086X
Date Issued
2024-05-08
Author(s)
Zih-An Chen
Cheng-Hsun Wu
Si-Han Wu
Chiung-Yin Huang
Kuo-Chen Wei
Yun Yen
I-Ting Chien
Sabiha Runa
Yi-Ping Chen
Peilin Chen
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.
Subjects
mesoporous silica nanoparticles
brain tumor
blood−brain barrier
the enhanced permeability and retention effect
doxorubicin
protein corona
Publisher
American Chemical Society (ACS)
Type
journal article