Enhanced Targeting of Cellular Delivery through Reactive Oxygen Species (ROS)-Activated Liposomes with Boronate-Caged Arginylglycylaspartic acid (RGD) Lipid

Liposomes are widely recognized for their roles in drug delivery systems due to their ability to encapsulate hydrophilic and hydrophobic drugs. However, their lack of selectivity and limited targeting of diseased cells often result in off-target effects, reducing their overall therapeutic efficacy. Additionally, achieving sufficient liposomal uptake by diseased cells remains a significant challenge. Surface modification is a valuable strategy employed to enhance liposomal drug delivery. This thesis will detail the design and synthesis of a boronate-caged arginyl glycyl aspartic acid (RGD) lipid aimed at improving liposome specificity and uptake through activation by reactive oxygen species (ROS). The RGD peptide was chosen for its high affinity for integrin receptors, which are overexpressed on cancer cells. Once activated by ROS, the uncaged RGD-lipid is expected to enhance receptor-mediated endocytosis, hence promoting the uptake of liposomes into cancer cells. Significant progress has been made in synthesizing key intermediates, providing a solid foundation for completing the final ROS-responsive RGD lipid. Upon completion, the compound will be thoroughly characterized to assess its activity. This research advances the development of more effective liposome-based drug delivery systems. It provides valuable insights into boronate caging chemistry, particularly its application to amino acids like arginine in the design of RGD-lipids.