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

in ACS nano by 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

TLDR

  • The study used tiny particles called mesoporous silica nanoparticles (MSNs) to deliver drugs to the brain. The blood-brain barrier (BBB) can be hard to get through, so the researchers made a special type of MSN that could better get through the BBB. They loaded the MSNs with a drug called doxorubicin (DOX) and found that the MSNs helped the drug get into the brain and kill brain tumors. The study also found that the MSNs had a special protein corona that helped them get through the BBB. This study supports the idea that MSNs could be used to treat brain tumors in the future.

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 (RMSN-PEG-TA) with a 25 nm size and a slight positive charge, which exhibits superior BBB penetration. Utilizing two-photon imaging, RMSN-PEG-TA particles remained in circulation for over 24 h, indicating significant traversal beyond the cerebrovascular realm. Importantly, DOX@RMSN-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@RMSN-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 RMSN-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.

Overview

  • The study focuses on the use of mesoporous silica nanoparticles (MSNs) for targeted brain tumor therapy and the challenges posed by the blood-brain barrier (BBB).
  • The methodology used includes the synthesis and characterization of a ligand-free PEGylated MSN variant (RMSN-PEG-TA) with a 25 nm size and a slight positive charge, as well as in vivo evaluations of its BBB penetration and brain accumulation of doxorubicin (DOX).
  • The primary objective of the study is to investigate the potential of ligand-free MSNs in treating brain tumors and to identify potential drug-nanoparticle design paradigms.

Comparative Analysis & Findings

  • RMSN-PEG-TA particles exhibited superior BBB penetration compared to other MSNs, with significant traversal beyond the cerebrovascular realm as observed through two-photon imaging. DOX@RMSN-PEG-TA achieved a 6-fold increase in brain accumulation compared to free DOX, harnessing the enhanced permeability and retention (EPR) effect. In vivo evaluations confirmed the potent inhibition of orthotopic glioma growth by DOX@RMSN-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 RMSN-PEG-TA, suggesting proteins such as apolipoprotein E and albumin could play pivotal roles in enabling its BBB penetration.

Implications and Future Directions

  • The study's findings highlight the potential of ligand-free MSNs in treating brain tumors and support the development of future drug-nanoparticle design paradigms. Limitations of the study include the need for further investigation into the long-term effects of RMSN-PEG-TA and its potential for use in other brain tumor models. Future research directions could explore the use of RMSN-PEG-TA in combination with other therapies or the development of new MSN variants with different properties for targeted brain tumor therapy.
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