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Mostafa Abdelhalim

Biochemistry, '21


Targeted Delivery of Liposomes using PARP Inhibitors to Treat Non-Small Cell Lung Cancer

Mentor: Ross I Berbeco, PhD (Dana Farber Cancer Institute)

Annually 221,200 cases of lung cancer are diagnosed and more than 158,040 patients die of Lung Cancer. Non-Small Cell Lung Cancer (NSCLC) accounts for 85% of the diagnosed cases, and is relatively insensitive to chemotherapy and radiation therapy. Novel therapies that are highly tumor specific with minimal systematic toxicity provide the necessary treatments to treat this disease. PARP inhibitor therapy exploits synthetic legality strategy by interfering with the DNA repair processes of the cancer cells in combination with DNA damaging agents like radiation or platinum. However, current oral delivery of PARP inhibitors is highly inefficient. In contrast, Injectable nano-particle formulations will lead to better bioavailability compared to the oral formation, and provide better targeting efficacy when compared to individual monotherapies. Liposome nano platforms carrying the PARP inhibitor drugs are optimized to provide a targeted therapy and have enhanced radiosensitization, enabling lower radiation doses with minimum systematic toxicities. The aim of this project is ensure the clinically relevant doses of PARP inhibitor drugs specific the lung tumor through targeted injectable liposome formulations. These will enable an effective Combination ChemoTherapy and Chemoradiation therapy, combining a DNA damaging agent with DNA repair blocking by a PARP inhibitor drug.

Figure: Schematic of proposed nanoplatforms for liposomes with PARP inhibitor drugs for targeted treatment of NSCLC. Source: