Theranostic Combination of Targeted Fluorescence Imaging and Photodynamic Therapy
Dr D O’Shea
Dr B Murphy
Monday, December 02, 2019
Competition Funded PhD Project (Students Worldwide)
Research Project Description: Photodynamic therapy (PDT) is a modern treatment that uses light to locally photosensitize tissues, resulting in the selective killing of targeted cells. Following administration of a photosensitizer, the cancerous lesion is irradiated with low energy light, promoting a set of photochemical reactions to damage the irradiated cell population, resulting in tumor ablation. Although PDT is an effective means of killing cancer cells, photosensitizers generally have little intrinsic selectivity for tumors. Increasing tumor selective accumulation could improve the efficacy of PDT and reduce any risk of side effects caused by photosensitizer accumulation in non-target tissue.
The various types of cells that comprise a tumor mass express many molecular receptors on their surface that distinguish them from normal cells. Nanobodies (smallest active targeting component of an antibody) can selectively recognize and target such surface receptors leading to delivery of a therapeutic payload exclusively at the desired site of disease. This research project will focus on exploring a less harmful approach to cancer therapy through nanobody derivatization to facilitate a controlled and definable conjugation to the highly efficient photosensitizing agents dibromo-BF2-chelatedazadipyrromethenes (ADPMs). The ADPM photosensitizer class has been developed within the O'Shea research team and their covalent combination with nanobody targeting agents would yield a drug-light combination that lends itself to two layers of selectivity. The inherent fluorescence of the ADPM class allows them to be readily visualized in vitro and in vivo thereby allowing for a theranostic approach as imaging of the diseased tissue during treatment.
Such an approach will increase treatment efficiency while reducing the undesirable side effects associated with traditional chemotherapies. This truly multidisciplinary project will advance knowledge in the fields of bio-conjugation chemistry, chemical biology and efficacy assessment of targeted PDT.