Pancreatic Tumor Microenvironmental Acidosis and Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles for Potent Radiosensitization

Authors

Pradipta Ranjan Rauta
Yuri Mackeyev
Keith Sanders
Joseph B K Kim
Valeria V Gonzalez
Yasmin Zahra
Muhammad A Shohayeb
Belal Abousaida
Geraldine V Vijay
Okan Tezcan
Paul Derry
Anton V Liopo
Eugene R Zubarev
Rickey Carter
Pankaj Singh
Sunil Krishnan

Publication Date

11-11-2022

Journal

Science Advances

DOI

10.1126/sciadv.abm9729

PMID

36367938

PMCID

PMC9651859

PubMedCentral® Posted Date

11-11-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate in the periphery and core of tumors without any signs of serum biochemical or hematological alterations, normal organ histopathological abnormalities, or overt deterioration in animal health. Furthermore, P(Glu-co-Lys)-GNRs penetrated the tumor microenvironment to accumulate in the hypoxic cores of tumors to potently radiosensitize heterotopic and orthotopic pancreatic cancers in vivo.

Keywords

Mice, Animals, Gold, Tumor Microenvironment, Lysine, Glutamic Acid, Nanotubes, Neoplasms, Acidosis, Hypoxia, Cell Line, Tumor

Published Open-Access

yes

Recommended Citation

Rauta, Pradipta Ranjan; Mackeyev, Yuri; Sanders, Keith; et al., "Pancreatic Tumor Microenvironmental Acidosis and Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles for Potent Radiosensitization" (2022). Faculty, Staff and Student Publications. 4653.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4653