Improving interstitial transport of macromolecules through reduction in cell volume fraction in tumor tissues

Interstitial transport of large molecules and nanoparticles is an important concern in nanomedicine-mediated cancer treatment. To that end, the current study was proposed to improve the transport through enlargement of extracellular space by treating tumors with hypertonic solution of mannitol and cytotoxic agents (e.g., ethacrynic acid [ECA]), which could effectively shrink and kill cells, respectively. In the study, the improvement in interstitial penetration of dextran was investigated ex vivo using rat fibrosarcoma tissues sectioned into 600 μm slices. Experimental data showed that the hypertonic solution was more effective than ECA for improving interstitial penetration of dextran with molecular weights ranging from 4000 to 2,000,000. The extent of improvement depended on the size of dextran molecules and the time when the treatment was applied. Results from the study suggested that increases in both size and connectedness of interstitial pathways were important for improvement of interstitial transport of large molecules and nanoparticles.From the Clinical EditorThis study reports on the optimization of interstitial transport both for large molecules and nanoparticles in nanomedicine-mediated cancer treatment. The study demonstrates that hypertonic solutions could efficiently lead to cancer cell shrinkage and more so than the applied cytotoxic agent thereby improving transport of chemotherapeutic entities.

Graphical AbstractInterstitial transport of macromolecules and nanoparticles in tumors can be improved through enlargement of extracellular space. In this study, the enlargement was achieved by treating tumor tissues with hypertonic solution of mannitol or a cytotoxic agent that could effectively shrink and kill cells. The treatments increased both the uniformity of distributions and the total amount of macromolecules diffused into tumor tissues.Figure optionsDownload high-quality image (159 K)Download as PowerPoint slide