Abstract
ABSTRACT Highly heterogeneous cancer cells represent the major challenge in clinical oncology for the treatment of human cancers. Novel therapeutic approaches that enable the application of personalized therapy for cancer patients hold great promise for effective treatment while minimizing systemic toxicity. We have developed an integrated cancer image-therapy protocol that takes advantages of multifunctionality of theranostic nanoparticles and advanced molecular imaging methods for biomarker-targeted tumor imaging and drug delivery, MRI monitoring therapeutic response, and optical image-guided surgery. Multifunctional magnetic iron oxide nanoparticles (IONPs) developed by our group are targeted to epidermal growth factor receptor, Her-2/Neu, and urokinase plasminogen activator receptor, which are biomarkers highly expressed in many types of human cancers. These receptor-targeted IONPs have capacity to carry single or multiple therapeutic agents for drug delivery, near infrared fluorescence and spectroscopic optical imaging, and magnetic resonance imaging (MRI). They are also designed to overcome physical and intrinsic barriers that reduce efficiency of drug delivery and confer drug resistance in human cancers. We have shown specificity and sensitivity of optical and MR imaging using the nanoparticles as targeted molecular contrast agents in orthotopic human breast, pancreatic, and ovarian cancer xenograft models. The development of biomarker targeted MRI nanoparticle probes should allow determining the level of biomarker expression in tumors using a non-invasive imaging approach for selection of the appropriate patients for targeted therapy. Based on the targeted imaging nanoparticles, we further developed methods to encapsulate or conjugate chemotherapy drugs into the nanoparticles. Efficacy of targeted therapy and MRI-monitoring drug delivery and response after systemic delivery of the theranostic nanoparticles has been demonstrated in orthotopic human breast, pancreatic and ovarian cancer xenograft models in nude mice. Since drug resistant residual tumors contain nanoparticles that produce optical signals, we applied hand-held optical imaging devices for detection and removal of drug resistant tumor lesions in the surgical cavity to prevent local recurrence and distant metastasis. The ultimate goal of our research is to translate this biomarker targeted therapy and image-guided treatment and surgery protocol into clinical applications for personalized management of cancer patients. Download : Download full-size image Fig. 1 . An integrated therapy-imaging approach for personalized therapy and effective treatment of drug-resistant cancers
Published Version
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