Drug Delivery Systems
Researchers: Souvik Ghosal
Intracellular Processing of Antibody- and Polymer-drug Conjugates
Cleavable, heteromultifunctional chemical cross-linkers have proven critical in a wide range of biological applications such as protein enrichment, conjugate-based drug delivery, and nanoparticle surface functionalization. However, traditional approaches for synthesizing this class of compounds suffer from various synthetic and functional limitations. Leveraging the oligoTEA synthesis methodology developed in our lab, we have recently addressed many of these limitations. In this research thrust, we utilize oligoTEA synthesis to design novel degradable scaffolds for the delivery of small molecule chemotherapeutics and molecular probes for the quantification of fundamental biological processes.
Cell Penetrating Oligothioetheramides (CPOTs)
Precise control over primary sequence and composition of oligoTEAs allows us to create synthetic alternatives to functional peptides. Compared to native peptides, oligoTEAs are proteolytically stable and yet easy to assemble at scale with structural diversity. In addition, access to direct modification of the oligoTEA backbone enables conformational control for tuning interactions between the binding motifs and the cell membrane. We have discovered a new class of non-charged cell-penetrating oligoTEAs (CPOTs) that undergo rapid cellular entry across a variety of cell lines (see video below). Experiments suggest that they undergo direct translocation across the cell membrane. We are currently focused on using CPOTs to deliver antibiotics against intracellular pathogens.
OligoTEA entry into Hela cells
Intracellular Protein and Peptide Delivery
The extracellular stability and intracellular delivery of proteins and peptides are significant impediments to their development, and effective delivery systems that promote their use are needed for their widespread adoption and clinical potential. Given the advantages of peptide-based ligands over small molecules (they can be designed from protein structural data against any POI, and they possess large protein-protein interaction surfaces for targeting POIs for which no known small molecule ligand exists) and the success of ionizable lipid nanoparticles (iLNPs) in the clinic, this project seeks to improve the stability, targeting and cytosolic transport of proteins , peptides and other biologics via iLNPs. We also investigate the use of polymer conjugates for improving intracellular delivery. Finally, these iLNPs, as well as other nanomaterials are being investigated for use in plant transformation in collaboration with the Van Eck lab.
Researchers: Souvik Ghosal, Azmain Alamgir, Amitava Chandra, Adithya Rangamani, and Allison Chen
Researchers: Souvik Ghosal, Meghna Bajaj