Systemic single agent therapies, or neo-adjuvant therapies for shrinking tumors prior to surgery, may indirectly lead to survival and propagation of drug resistant and more malignant cancer cells because of inter and intra-tumoral heterogeneity. Breast and many other cancers are highly heritable, yet most causative variants are unknown. Of the known risk variants, most are considered tumor cell-autonomous, with far less emphasis placed on testing germline variants that impact the tumor microenvironment, that is expected to play a major role both in tumor cell proliferation but also in chemo or radiotherapy delivery and response. A critical need exists for therapies which are impervious to drug resistance mechanisms and effective in heterogeneous tumor environment, with minimal off-target toxicity. Light activated and tumor selective nanoparticle based thermal ablation fulfills the criteria for such a therapy, and its validation and optimization in models with host germline based vascular micro-environment variation can generate novel insights into nano-drug delivery mechanisms and potentially create a major breakthrough in reducing the mortality and morbidity associated with breast cancer treatment. We describe a new generation of sub 100 nm theranostic nanoparticles which combine organic fluorophore free native luminescence in extended near-infrared or short wave IR (SWIR) region (700-1800 nm) enabling low scatter and background free tumor visualization, T1 weighted MRI contrast for cross-sectional imaging and therapy planning, and  X-ray contrast with strong plasmon resonance in near-infrared for interventional radiology guided photothermal ablation. While most nanoparticle therapies rely on testing and validation on human tumor cell line xenografts only in immune-compromised ~20g mouse models leading to poor predictability of eventual clinical success, we demonstrate that germline host microenvironment variation in vascular perfusion, and tumor architecture play a critical role in both nanoparticle uptake and response to nanoparticle mediated photothermal ablation of breast cancer.<br/>

Impact of host germline variation and tumor microenvironment on plasmonic nanoparticle based photo-thermal therapy

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.