A cell- surface polymer reptation mechanism for tumor transendothelial transport of macromolecules.

Polymer reptation is a process by which flexible linear polymers can migrate around obstacles and through pores and around other polymer molecules. It has successfully described quantitative behavior of polymer melts and has been invoked in explaining DNA separation according to length in sequencing gels. This mechanism may therefore be useful in delivering contrast agents or therapeutic drugs to tumors as these must traverse from the intravascular space through the tumor endothelial junction gaps and into the tumor.

Tumor microvasculature: endothelial leakiness and endothelial pore size distribution in a breast cancer model.

Tumor endothelial leakiness is quantified in a rat mammary adenocarcinoma model using dynamic contrast enhancement MRI and contrast agents of widely varying sizes. The contrast agents were constructed to be of globular configuration and have their uptake rate into tumor interstitium be driven by the same diffusion process and limited only by the availability of endothelial pores of passable size. It was observed that the endothelial pore distribution has a steep power law dependence on size, r(-) (β), with an exponent of -4.

A multimodal contrast agent for preoperative MR Imaging and intraoperative tumor margin delineation.

We have constructed a multimodal contrast agent suitable for near-infrared, NIR, fluorescent imaging as well as magnetic resonance imaging, MRI. This class of agents may be useful for preoperative tumor localization and tumor functional evaluation and for intraoperative delineation of tumor margins. We have covalently attached dyes of the cyanine family to a previously described polymeric contrast agent, Gd-DTPA-polylysine, of an extended, uncoiled conformation.

The role of molecular conformation on tumor uptake of polymeric contrast agents.

Rationale And Objective: We wanted to test the hypothesis that linear extended polymers are able to translocate across compromised endothelia to a much higher degree than polymers that are in a coiled configuration. The basis for this hypothesis is the concept of polymer reptation, a process allowing linear polymers to move around fixed obstacles and through small pores.

Materials And Methods: The conjugation of polylysine with DTPA was varied from 55% to 95% of lysine moieties for a fixed polymer degree of polymerization.

Conformation and structure of polymeric contrast agents for medical imaging.

The structure of Gd-DTPA-polylysine, Gd-DOTA-polylysine, Gd-SCN-Bz-DOTA-polylysine, and Gd-DTPA-poly(glu:lys) was investigated with circular dichroism, gel permeation chromatography, low angle light scattering, and proton longitudinal relaxivity. Molecular modeling calculations were performed and predicted helical secondary structure for charged Gd-chelator residues, i.e.