Surface-grafted polyethylene glycol conformation impacts the transport of PEG-functionalized liposomes through a tumour extracellular matrix model

Abstract

The effect of surface PEGylation on nanoparticle transport through an extracellular matrix (ECM) is an important determinant for tumor targeting success. Fluorescent stealth liposomes (base lipid DOPC) were prepared incorporating different proportions of PEG-grafted lipids (2.5, 5 and 10% of the total lipid content) for a series of PEG molecular weights (1000, 2000 and 5000 Da). The ECM was modelled using a collagen matrix. The kinetics of PEGylated liposome adhesion to and transport in collagen matrices were tracked using fluorescence correlation spectroscopy (FCS) and confocal microscopy, respectively.Generalized least square regressions were used to determine the temporal correlations between PEG molecular weight, surface density and conformation, and the liposome transport in a collagen hydrogel over 15 hours. PEG conformation determined the interaction of liposomes with the collagen hydrogel and their transport behaviour. Interestingly, liposomes with mushroom PEG conformation accumulated on the interface of the collagen hydrogel, creating a dense liposomal front with short diffusion distances into the hydrogels. On the other hand, liposomes with dense brush PEG conformation interacted to a lesser extent with the collagen hydrogel and diffused to longer distances. In conclusion, a better understanding of PEG surface coating as a modifier of transport in a model ECM matrix has resulted. This knowledge will improve design of future liposomal drug carrier systems.

Synthesis and modification of uniform PEG-neridronate-modified magnetic nanoparticles determines prolonged blood circulation and biodistribution in a mouse preclinical model

“…The highest PEG grafting density was found on the 20 nm particles (1.02 PEG/nm 2 ), while the lowest density was found on the 31 nm particles (0.76 PEG/nm 2 ; Table 1). In theory, if the molecular weight and surface density of PEG are known, it is possible to predict its conformation 38 . The grafting density controls the conformation of PEG chains on the surface, which can be brush-like or mushroom-like.…”

Optimizing PEGylation of TiO2 Nanocrystals through a Combined Experimental and Computational Study

“…This kind of simplified model has been used for years to define polymer shell structures. 37−41 More recently, it has been further refined by Labouta et al 42 according to the following scheme: for R F / D m < 1, PEG chains assume a mushroom conformation; for 1 < R F / D m < 2, a brush one; and for R F / D m > 2, the conformation is of a dense brush.…”

Bi-Ligand Modification of Nanoparticles: An Effective Tool for Surface-Enhanced Raman Spectrometry in Salinated Environments

“…The conformation of PEG is influenced by its surface density. While at a high level of surface saturation this polymer creates a so-called brush , the desired mushroom-like areas, which do not block the surface of NPs, are formed only at the low saturation [16]. Using dynamic light scattering we investigated the nanoparticle size of three colloids treated by various modification protocols.…”