Executive Summary : | Unlike prokaryotes, eukaryotic cells contain many independent intracellular compartments separated from the cytoplasm by membranes called organelles; such as a nucleus, mitochondria, Golgi body, Endoplasmic Reticulum (ER), ribosome, lysosome, etc. Each of these organelles has unique structural characteristics and plays a distinct role in various physiological and biochemical reactions. They can function both independently and cooperatively. Therefore, any dysfunction in even a single organelle may hamper the smooth functional harmony of the whole cell gradually giving rise to various diseases such as metabolic disorders, cancer, neurodegenerative and cardiovascular diseases, etc. For example, the damage in mitochondria results in the apoptosis of cells; genetic disorders may lead to abnormal function of intracellular proteins in lysosome or peroxisome. Thus, the organelle responsible for the dysfunction needs to be treated with the supply of appropriate therapeutic agents like specific protein/non-protein drugs, DNA/RNA sequences. To this end, efficient permeation of the drug to the targeted intracellular organelle is a prerequisite for its pharmacological efficacy and efficiency. subcellularly-acting drugs are characterized by inherent pharmacokinetic limitation which includes high permeability through different biological barriers (capillary walls, cell membranes, and organelle membranes). High permeability could also lead to extensive drug accumulation at the site of the desired action causing some adverse effects on the cell. To circumvent these pharmacokinetic limitations a new idea of drug delivery system (DDs) has been introduced to the biomedical research field. Peptides are among the most extensively used DDss due to their standard synthetic protocol, structural tunability, bio-diversity, and non-toxicity. While one can use their ability to self-assemble into a variety of desired nanostructures, can also improve the ability to encapsulate and release drugs just by the rational design of a peptide sequence. In that regard, cyclic peptides are special as they can stack together by parallel or anti-parallel beta-sheet-like hydrogen bonding to construct a supramolecular cyclic peptide nanotube (sCPNT), that can encapsulate the drug in its core until disrupted. Further, to permeate the cellular barriers and improve the solubility of the sCPNs, a variety of linear peptides are attached covalently without any compromise to the nanostructures. The linear peptides like Nuclear Localization Peptides (NLs) for the nucleus, KDEL receptor targeting peptides for ER, αvβâ receptor for cell membrane, and so on, designed to take care of the biological barriers are well accomplished. Hence, the focus of this project is to make a combination of cyclic and linear peptides having different functionalities to deliver therapeutic agents into targeted sub-cellular organelles. |