Peptides are being increasingly applied across clinical medicine, including applications in cancer, cardiovascular diseases, or metabolic disorders. Importantly, short peptides that include phenylalanine residue were found to have self-assembling properties that could be used to stabilize nanostructures. The goal of this study is to develop a peptide-stabilized nanoparticle (NP)–based system for delivery of anticancer agents at high dosages. This work explores self-assembling tri- and hexapeptides as coating materials for polymeric and oil-based nanoparticles (NPs) and their delivery of cytotoxic platinum-based drugs as well as antiangiogenic combretastatin A4 (CA4).<br/><br/>The average diameter of the NPs was 75 nm with a low polydispersity index (PDI) of 0.115. The Zeta potential of the NPs was -35.8 mV indicating good colloidal stability of the NP system. The NPs were stable in serum for 72 hours, demonstrating suitability for biological applications. The RGD motif of the peptide, known to preferentially bind to αvβ3 integrin implicated in tumor angiogenesis, was exploited as the NP’s targeting component. The NPs were tested <i>in vitro</i>with model human umbilical cord vascular endothelial cells (HUVEC), as well as with ovarian cancer (OC) cells. Imaging studies confirmed NP cellular uptake and an equal distribution throughout the cytosolic compartment. Viability studies demonstrated high biological activity of the NPs towards HUVEC and moderate activity in OC cells. Uniquely, the NPs were tested with patient-derived OC cells that we established from patients with highly aggressive, platinum-resistant disease. Preliminary findings indicate that the NPs entered all tested cells. In addition, we evaluated the potential of the NPs (no drugs) to target solid tumors in a subcutaneous model of OC. The NPs were shown to be effectively accumulated at the tumor site, with sustained retention even up to four days post injection. These results suggest that peptide-coated NPs can potentially find applications in OC therapy.

Engineering and validation of peptide-stabilized nanomaterials for drug delivery and cancer therapy

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.