David H Thompson
Purdue University, USA
Title: Peptide-targeted immunotherapeutic nanoparticles for intravesical treatment of bladder cancer
Biography
Biography: David H Thompson
Abstract
Bladder carcinoma is the most expensive tumor type to treat on a cost per patient basis from diagnosis to death. Intravesical bacillus Calmette Guerin (BCG) instillation is the only approved immunotherapy for treatment of superficial bladder carcinoma. Unfortunately, frequent relapses, high local morbidity and the risk of systemic mycobacterial infection are significant limitations of this therapeutic approach. BCG utilizes an adhesin protein known as fibronectin attachment protein that contains a critical peptide sequence for binding to bladder tumor cells. Previously, we have shown that multivalent peptide targeted liposomes promote fibronectin-integrin microaggregation and internalization via a caveolae dependent mechanism with a strict ï‚£70 nm size cutoff. Microfluidics offers the potential of formulating scale size controlled nanoparticles in a reproducible manner. Using a chemtrix flow reactor system, we have developed pH sensitive CpG lipid nanoparticles and organic solvent purified elastin like peptide complexes for targeted delivery of these oligonucleotides to activate cells expressing toll like receptor 9 (TLR)9 to mount an innate immune response characterized by the production of Th1 and proinflammatory cytokines. Since (TLR)9 receptors are located within intracellular acidic compartments, such as endosomes and lysosomes, these vehicles have been designed to release their CpG cargo after internalization. Data showing that these peptide targeted nanoparticles specifically bind to and are internalized by bladder tumor cells will be presented. Confocal studies have also been performed to track the cellular fate of these targeted carrier systems. Our findings show that only the pH-sensitive formulations are capable of releasing their payload after 12 h and stimulating a cytokine response. Collectively, our findings suggest that these peptide targeted immunostimulatory complexes may be at low-risk, highly efficient alternative to BCG immunotherapy.