Development of cancer imaging and therapeutic nanoparticles has to address several major challenges in cancer therapy. Highly heterogeneous human cancers require integration of imaging-therapy approaches for personalized cancer treatment to maximize intratumoral drug delivery, and timely assessing delivery efficiency and tumor response.  Magnetic iron oxide nanoparticles (IONPs) are promising biodegradable and MRI capable nanoparticles for the development of theranostic nanoparticles for clinical applications.  We have developed NIR-dye labeled and uPAR or IGF1R targeted IONPs that are able to target cancer cells and tumor stromal fibroblasts and macrophages. Efficiency of targeted delivery, intratumoral distribution and therapeutic efficacy were examined in human pancreatic or triple negative breast cancer (TNBC) patient tissue derived xenograft (PDX) models as well as transgenic mouse tumor models. We found that this targeting strategy led to an increased retention of the nanoparticles in tumor tissues by active vessel targeting (uPAR) and passive targeting (uPAR and IGF1R). A high level of targeted nanoparticles accumulated in the peripheral tumor areas and a low level in the tumor center following repeated systemic administration.  Furthermore, repeated injections of receptor-targeted theranostic nanoparticles carrying chemotherapy drugs resulted in induction of cell death in cancer cells and tumor stromal cells. Breaking stromal cellular barriers by theranostic nanoparticles led to improved intratumoral distribution and tumor cell delivery of the nanoparticles in the tumor center. In pancreatic and TNBC PDX tumor models, uPAR and IGF1R targeted delivery of theranostic nanoparticles enabled NIR optical and MR imaging of targeted drug delivery and monitoring tumor responses to therapy. Significant tumor growth inhibition and induction of tumor cell death were also found in those tumor models. Therefore, those receptor targeted theranostic nanoparticles have the potential for translation of image-guided and targeted cancer therapy of stroma rich human tumors.   <br/>

Rationally designed theranostic nanoparticles for applications of precision oncology for image-guided cancer treatment

251st National Meeting (2016)

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