Development of Anti-PD-L1 Immunoliposomes for Antitumor Drug Delivery against skin cancer

Nowadays, Liposomes are considered as essential nanocarriers in drug delivery for various hydrophilic and hydrophobic active molecules due to their significantly higher Biocompatibility, Biodegradability and Lower immunogenicity compared to other delivery systems. Liposome surface modification enhances its ability to increase its circulation half-life and targeting therapy potential. Moreover, such modifications improve the efficacy of treatment by accumulating the liposomes at tumor sites. This Project aimed to develop and optimize immunoliposomes for targeted Drug delivery, Incorporating Vismodegib as the therapeutic agent. Initially, the stealth liposomes were prepared composed of soy phosphatidylcholine (SPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene (DSPE-PEG) to create a stable and stealth nanocarrier system. A wide range of Formulations was evaluated to reach the optimal liposome composition, focusing on enhancing the encapsulation efficiency and stability of the liposome. Once the optimal liposome formulation was obtained, the targeting capacity was improved by conjugating Fab' fragment of the monoclonal antibody, Atezolizumab, on the surface of the liposome to generate Immunoliposomes with specific affinity for cancer cells. Atezolizumab targets the programmed cell death ligand 1 (PD-L1) receptor, which is over expressed in various cancer types. Skin cancer, in both melanoma and non-melanoma forms, plays a critical role in the worldwide mortality rate. These tumors often show overexpression of PD-L1 and display abnormal, continuous activation of the Hedgehog (Hh) signaling pathway. Therefore, the formulated liposome carries Vismodegib, which is a selective (Hh) inhibitor, and is conjugated with Fab' fragments that recognize the PD-L1 receptor. The immunoliposomes were tested in vitro using two human cell lines: SK-MEL-28 (melanoma) and HaCaT (keratinocytes). The SK-MEL-28 line will assess the targeting efficacy of the drug-loaded immunoliposomes against melanoma cells, while the HaCaT line will serve as a control to evaluate the selectivity and safety of the formulation in non-cancerous cells. This study aims to demonstrate the potential of antibody-targeted immunoliposomes as an effective and selective drug delivery system for treating melanoma, providing valuable insights for future clinical applications.