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

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/659524 doi: bioRxiv preprint indicated by the upward shift in the ensemble-averaged mean squared displacement (MSD) at a time scale of 1 sec (Figure 6a) . Both PEGylation and iRGD-coating improved the MSD of the nanoparticle 10-and 15-fold, respectively (Figure 6b) . This improvement is most likely due to their hydrophilic and less negative surface charge properties. Interestingly, the P4-peptide coating improved the MSD of the nanoparticle 40-fold, exhibiting greater improvement than the other coatings. Examining the individual particle diffusivity binned together as ensemble measurements through the tumor ECM, there is a shift in particle distribution towards higher MSD upon PEG or P4-peptide coating (Figures 6c and 6d) . In particular, there is a larger fraction of peptide-coated nanoparticles that are mobile and demonstrate rapid diffusivity (log MSD is greater than -0.5) compared to PEG-coated nanoparticles (5% to 1%, respectively). Given that the same molar ratio was used to conjugate peptide/PEG onto nanoparticles, this result suggests that the optimal peptide coating improves unhindered particle transport through the tumor ECM.