| Autor: |
Chen, Zih-An, Wu, Cheng-Hsun, Wu, Si-Han, Huang, Chiung-Yin, Mou, Chung-Yuan, Wei, Kuo-Chen, Yen, Yun, Chien, I-Ting, Runa, Sabiha, Chen, Yi-Ping, Chen, Peilin |
| Zdroj: |
ACS Nano; May 2024, Vol. 18 Issue: 20 p12716-12736, 21p |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
