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PET and MRI Guided Irradiation of a Glioblastoma Rat Model Using a Micro-irradiator
Published on: December 28, 2017
Image-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment
Oliver K Appelbe1,2, Qingbei Zhang1,2, Charles A Pelizzari3
1Ludwig Center for Metastasis Research, The University of Chicago , 5758 South Maryland Avenue, MC 9006, Chicago, Illinois 60637, United States.
Abstract:
Current strategies to target tumors with nanomedicines rely on passive delivery via the enhanced permeability and retention effect, leveraging the disorganized tumor microvasculature to promote macromolecule extravasation and the reduced lymphatic and venous drainage that favor retention. Nonetheless, FDA approvals and clinical use of nanomedicines have lagged, reflecting failure to display superiority over conventional formulations. Here, we have exploited image-guided X-irradiation to augment nanoparticle accumulation in tumors. A single 5 Gy dose of radiation, below that required to significantly delay tumor growth, can markedly enhance delivery of macromolecules and nanoparticles. The radiation effect was independent of endothelial cell integrity, suggesting a primary role for damage to microvascular pericytes and/or interstitial extracellular matrix. Significantly, radiation-guided delivery potentiated the therapeutic effects of PEGylated liposomal doxorubicin on experimental tumors. Applied to patients, these results suggest repurposing image-guided radiotherapy as a tool to guide cancer nanomedicine delivery, enhancing local control for primary tumors and metastatic disease while limiting systemic toxicity.
Insights
Image-guided X-irradiation enhances nanoparticle delivery to tumors. This novel approach improves nanomedicine efficacy, offering a new strategy for cancer treatment and potentially increasing local tumor control.
Area of Science:
- Biomedical Engineering
- Radiotherapy
- Nanomedicine
Background:
- Current nanomedicine delivery to tumors relies on the passive enhanced permeability and retention (EPR) effect.
- Limitations in nanomedicine efficacy and FDA approvals highlight the need for improved delivery strategies.
Purpose of the Study:
- To investigate the use of image-guided X-irradiation to enhance nanoparticle accumulation in tumors.
- To evaluate the therapeutic potentiation of nanomedicines when combined with radiation-guided delivery.
Main Methods:
- Administered a single 5 Gy dose of X-irradiation to experimental tumors.
- Assessed the impact of irradiation on macromolecule and nanoparticle delivery.
- Evaluated the therapeutic efficacy of PEGylated liposomal doxorubicin in combination with radiation-guided delivery.
Main Results:
- A sub-therapeutic dose of X-irradiation significantly enhanced nanoparticle and macromolecule delivery to tumors.
- The radiation-induced enhancement was independent of endothelial cell integrity, suggesting pericyte or extracellular matrix damage.
- Radiation-guided delivery of PEGylated liposomal doxorubicin potentiated therapeutic effects in experimental tumors.
Conclusions:
- Image-guided radiotherapy can be repurposed to enhance cancer nanomedicine delivery.
- This strategy holds potential for improving local control of primary and metastatic tumors.
- Combining radiotherapy with nanomedicine may improve therapeutic outcomes while limiting systemic toxicity.
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