Image-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment

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.