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Published on: October 27, 2014
Optical blood-brain-tumor barrier modulation expands therapeutic options for glioblastoma treatment
Qi Cai1, Xiaoqing Li2, Hejian Xiong1
1Department of Mechanical Engineering, the University of Texas at Dallas, Richardson, TX, 75080, USA.
Abstract:
The treatment of glioblastoma has limited clinical progress over the past decade, partly due to the lack of effective drug delivery strategies across the blood-brain-tumor barrier. Moreover, discrepancies between preclinical and clinical outcomes demand a reliable translational platform that can precisely recapitulate the characteristics of human glioblastoma. Here we analyze the intratumoral blood-brain-tumor barrier heterogeneity in human glioblastoma and characterize two genetically engineered models in female mice that recapitulate two important glioma phenotypes, including the diffusely infiltrative tumor margin and angiogenic core. We show that pulsed laser excitation of vascular-targeted gold nanoparticles non-invasively and reversibly modulates the blood-brain-tumor barrier permeability (optoBBTB) and enhances the delivery of paclitaxel in these two models. The treatment reduces the tumor volume by 6 and 2.4-fold and prolongs the survival by 50% and 33%, respectively. Since paclitaxel does not penetrate the blood-brain-tumor barrier and is abandoned for glioblastoma treatment following its failure in early-phase clinical trials, our results raise the possibility of reevaluating a number of potent anticancer drugs by combining them with strategies to increase blood-brain-tumor barrier permeability. Our study reveals that optoBBTB significantly improves therapeutic delivery and has the potential to facilitate future drug evaluation for cancers in the central nervous system.
Insights
Researchers developed a novel optoBBTB method using gold nanoparticles and lasers to enhance drug delivery for glioblastoma. This approach improves paclitaxel delivery, reducing tumor volume and extending survival in preclinical models.
Area of Science:
- Neuro-oncology
- Nanomedicine
- Biomedical Engineering
Background:
- Glioblastoma treatment faces challenges due to the blood-brain-tumor barrier (BBTB) limiting drug efficacy.
- Preclinical models often fail to accurately represent human glioblastoma, hindering therapeutic development.
Purpose of the Study:
- To analyze BBTB heterogeneity in human glioblastoma.
- To develop and validate genetically engineered mouse models for glioblastoma research.
- To investigate a non-invasive method for modulating BBTB permeability and enhancing drug delivery.
Main Methods:
- Characterization of intratumoral BBTB heterogeneity in human glioblastoma.
- Development of two genetically engineered mouse models mimicking glioma phenotypes.
- Application of pulsed laser excitation with vascular-targeted gold nanoparticles to modulate BBTB (optoBBTB).
- Assessment of paclitaxel delivery and therapeutic efficacy in preclinical models.
Main Results:
- The optoBBTB method non-invasively and reversibly modulated BBTB permeability.
- Paclitaxel delivery was significantly enhanced in both glioblastoma models.
- Tumor volume was reduced by 6-fold and 2.4-fold, with survival prolonged by 50% and 33% respectively.
- The approach demonstrated potential for re-evaluating existing drugs for glioblastoma treatment.
Conclusions:
- OptoBBTB is a promising strategy for overcoming the BBTB and improving therapeutic delivery in glioblastoma.
- This technology facilitates future drug evaluation for central nervous system cancers.
- The developed mouse models offer a reliable platform for translational glioblastoma research.
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