Hyperfluorescence Imaging of Kidney Cancer Enabled by Renal Secretion Pathway Dependent Efflux Transport

Bujie Du, Yue Chong, Xingya Jiang, Mengxiao Yu, U. Gling Lo, Andrew Dang, Yu An Chen, Siqing Li, Elizabeth Hernandez, Jason C. Lin, Jer Tsong Hsieh, Jie Zheng

Research output: Contribution to journalArticlepeer-review

Abstract

Renal tubular secretion is an active efflux pathway for the kidneys to remove molecules but has yet to be used to enhance kidney cancer targeting. We report indocyanine green (ICG) conjugated with a 2100 Da PEG molecule (ICG-PEG45) as a renal-tubule-secreted near-infrared-emitting fluorophore for hyperfluorescence imaging of kidney cancers, which cannot be achieved with hepatobiliary- and glomerular-clearable ICG. This pathway-dependent targeting of kidney cancer arises from the fact that the secretion pathway enables ICG-PEG45 to be effectively effluxed out of normal proximal tubules through P-glycoprotein transporter while being retained in cancerous kidney tissues with low P-glycoprotein expression. Tuning elimination pathways and utilizing different efflux kinetics of medical agents in normal and diseased tissues could be a new strategy for tackling challenges in disease diagnosis and treatments that cannot be addressed with passive and ligand-receptor-mediated active targeting.

Original languageEnglish (US)
Pages (from-to)351-359
Number of pages9
JournalAngewandte Chemie - International Edition
Volume60
Issue number1
DOIs
StatePublished - Jan 4 2021

Keywords

  • PEGylation
  • imaging agents
  • indocyanine green
  • renal cell carcinoma
  • tumor imaging

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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