Identification of peptide coatings that enhance diffusive transport of nanoparticles through the tumor microenvironment

Rashmi Mohanty; Xinquan Liu; Jae You Kim; Xiujuan Peng; Sahil Bhandari; Jasmim Leal; Dhivya Arasappan; Dennis C. Wylie; Tony Dong; Debadyuti Ghosh

Select peptide-presenting clones exhibit rapid transport, as evidenced by an significant increase in their tumor transport compared to the negative control. Through systematic mutagenesis of the model P4 peptide-presenting phage, we demonstrate that alterations of the physicochemical properties and the configuration of the peptide impacts transport. We hypothesize that the mutations change the binding affinity of the peptide with the ECM, thereby hindering their diffusion. The role of binding interactions and its impact on diffusion has been observed in peptide transport in mucus and cartilage; however, further studies are warranted to confirm this mechanism in the tumor microenvironment. The model peptide-presenting phage exhibited increased uptake in tumor tissue compared to the negative control. Importantly, peptides are promising as surface coatings to improve nanoparticle transport through the tumor microenvironment. Peptide coatings reduce the hindered transport of uncoated nanoparticles through the tumor ECM and demonstrate improved transport compared to gold standard polymeric coatings. Importantly, there is a greater fraction of nanoparticles that achieve rapid transport in tumor tissues with our peptide coating All rights reserved. No reuse allowed without permission.