Image-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment

• DOI: 10.1021/acs.molpharmaceut.6b00465
• Publication Date: 2016-08-25T12:41:13Z
• Authors: Oliver K. Appelbe; Qingbei Zhang; Charles A. Pelizzari; Ralph R. Weichsel...; Stephen J. Kron
• Keywords: Extravasation; Molecular Imaging

Current strategies to target tumors with nanomedicines rely on passive delivery via the enhanced permeability and retention effect, leveraging disorganized tumor microvasculature promote macromolecule extravasation reduced lymphatic venous drainage that favor retention. Nonetheless, FDA approvals clinical use of have lagged, reflecting failure display superiority over conventional formulations. Here, we exploited image-guided X-irradiation augment nanoparticle accumulation in tumors. A single 5 Gy dose radiation, below required significantly delay growth, can markedly enhance macromolecules nanoparticles. The radiation effect was independent endothelial cell integrity, suggesting a primary role for damage microvascular pericytes and/or interstitial extracellular matrix. Significantly, radiation-guided potentiated therapeutic effects PEGylated liposomal doxorubicin experimental Applied patients, these results suggest repurposing radiotherapy as tool guide cancer nanomedicine delivery, enhancing local control metastatic disease while limiting systemic toxicity.