On 29 January at 15:00 Prakash Lingasamy will defend his doctoral thesis “Development of multitargeted tumor penetrating peptides”.
Professor Tambet Teesalu, University of Tartu
Professor Angelo Corti, Università Vita-Salute San Raffaele (Italy)
Precision targeting of cancer suffers from spatiotemporal heterogeneity, low capacity, and reduced availability of receptors of affinity ligands. We hypothesized that multitargeted peptide ligands could improve affinity tumor targeting for more efficacious cancer therapy.
Various monospecific affinity targeting strategies for cancer delivery have been employed with limited success due to tumor heterogeneity and limited quantities of available receptors. The research work presented in this thesis describes development of multi-targeted tumor penetrating peptides for simultaneous targeting of two or more markers in the tumor microenvironment to overcome the spatiotemporal heterogeneity in the expression of target molecules and to address the issues related to the limited number of systemically available target receptors. The peptides were identified using cell-free biopanning and validated in vivo using a panel of clinically relevant tumor models. Our studies established the preclinical proof of utility for the peptide-guided precision delivery for NPs loaded with anticancer payloads and imaging agents to solid tumors. The current work focused on the development of novel multitargeted tumor penetrating peptides against a stable and abundant component in solid tumors, extracellular matrix (ECM). We have used a panel of strategies and advanced techniques to identify ECM-specific peptidic ligands and to study tumor homing, biodistribution, and therapeutic efficacy of peptide guided nanoparticles on purified recombinant proteins, cultured cells, and in vivo animal models. The homing peptides identified in this work are translationally relevant as they are not species-specific and bind to both mouse and human target proteins.
These results warrant future efforts on development of these novel multitargeted homing peptides towards clinical.
Please note, the defence will be held via video bridge.