Boosting photo-induced cancer therapies through real-time image guidance Summary The goal of this project is to significantly improve the efficacy, safety, and efficiency o photo-induced cancer therapies using a novel real-time image-guided therapeutic device. The photo-induced therapy is a promising cancer treatment method that uses heat or toxic chemicals released from functional nanoparticles (NPs) induced by near-infrared (NIR) light to selectively destroy cancer cells with minimal invasiveness. Although multifunctional NPs, such as copper sulfide (CuS) with radioisotope 64Cu, are able to serve both imaging and therapeutic purposes, the lack of a multifunctional device results in separation of tumor imaging and therapeutic NIR light delivery. This separation can lead to a less efficient therapy, unnecessary destruction of normal tissues, or a more severe consequence of incomplete destruction of the tumor. To tackle these challenging problems, we propose to develop the Beta Image Guided Light-Induced Therapeutic devicE (BIGLITE), a superb multi-functional device that integrates beta imaging and therapeutic NIR laser delivery capabilities to enable simultaneous imaging and photo-induced therapy. The key idea of BIGLITE is to adaptively lock the NIR laser delivery site onto the desired location inside the tumor (target) using real-time images and to deliver NIR laser only when the target is locked on. The precision delivery of laser enabled by BIGLITE can boost photo-induced therapies on three aspects: i) more complete cancerous cell destruction while sparing healthy ones largely; ii) significantly increased laser power for much faster treatment; and iii) lowered NP dose for increased safety. The goal of this project will be achieved by the following specific aims: 1) development of BIGLITE hardware and software. The hardware is composed of a position-sensitive gas electron multiplier (GEM) detector and a digital camera as an imaging component of the BIGLITE for functional beta images and surface structural imaging, respectively, and an embedded NIR fiber as a therapeutic component. The software includes advanced imaging modeling and spatiotemporal processing algorithms utilizing functional and structural images to enable precise real-time image guided delivery of NIR light; and 2) determination of the optimal treatment conditions and in vitro and in vivo assessment of the photothermal therapy performance of BIGLITE using PEG-CuS nanoparticles. Founded on the research team's experience on GEM detector development, advanced imaging processing and nanoparticle-based photo-induced therapies, it is envisioned that BIGLITE will succeed and become a preclinical evaluation tool for the novel theranostic NPs development and a clinical tool for the treatment of subcutaneous tumors, the cleanup of tumor boundaries in surgical resection of major tumors in critical organs, or the destruction of small occult and unrespectable tumors in locally advanced cancers along with the clinical translation of multifunctional NPs. A significant involvement of undergraduate/graduate students in this research will be fostered.
The proposed research is highly relevant to public health because the development of a Beta Image Guided Light-Induced Therapeutic devicE (BIGLITE) can significantly improve the efficacy and safety of photo-induced therapy of cancer. BIGLITE can utilize the imaging reporters carried by multifunctional nanoparticles to guide the delivery of near-infrared (NIR) light to the tumor with high precision. This high precision will allow a high laser power and lead to unprecedentedly effective, fast and safe photo-induced therapies of cancer.
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