Design and Development of Targeted-Liposome for drug delivery to lung cancer by exploiting a vulnerability induced by radiotherapy

Abstract The proposed drug development will result in the design and development of a ligand targeted liposomeLTLthat will aid in the targeted delivery of therapeutics to patients with Non Small Cell Lung CancerNSCLCWe propose an innovative active targeting strategy and our technology exploits the stress response that occurs within the cancer cells following exposure to ionizing radiationThis liposome targets the neoantigen Glucose Regulated ProteinGRPwhich is overexpressed in NSCLC and is further induced when cancer cells are exposed to radiationa standard of care for patients with NSCLSCFor patients with NSCLCtheyear overall survival rate isThe difficulty in treatment is partly due to genetic tumor heterogeneitypatient heterogeneityinduced immunosuppressionand limited drug penetrationThe impact of current cytotoxic chemotherapies on NSCLC is limited by lack of specificity hence the attendant cytotoxicity to normal cellsresistance to therapy and disease recurrenceWe identified GRPthrough the use of bacteriophage displayed peptide libraries and subsequent affinity purification of surface proteins from cancerThe proposed research will advance our lead LTL s towards IND enabling studiesWe will design and optimize a new peptidomimetic based on modeling of our parent peptide to achieve stronger specificity and prolonged circulationWe will synthesize the peptidomimetics and generate the LTL and characterize the sameFurthermorewe will demonstrate cancer specificity and sensitivity of the LTL s using in vitro and in vivo assaysAt the end of the project termwe will have determined and validated the feasibility of our new LTL as an effective payload carrier and hence a therapeutic agent in NSCLCIn line with our long term goal in the next phase of the projectwe study the bio distribution and drug loading capability and efficacy by conducting studies that will determine the therapeutic effects of peptide conjugated cancer pharmaceuticals Narrative We discovered a new inducible molecular target for lung cancerGlucose Regulated ProteinGRPand designed a peptide that can target GRPThe goal of the proposed research is to design and develop a novel peptide from the parent sequence and synthesize a Ligand Targeted Liposome that can carry chemotherapeutic payload for targeted deliveryUsing such targeted delivery we can achieve enhanced safetyefficacyand bioavailability of the drugs