Functionalizing Collagen with Vessel-Penetrating Two-Photon Phosphorescence Probes: A New In Vivo Strategy to Map Oxygen Concentration in Tumor Microenvironment and Tissue Ischemia

Adv Sci (Weinh). 2021 Oct;8(20):e2102788. doi: 10.1002/advs.202102788. Epub 2021 Aug 19.

Abstract

The encapsulation and/or surface modification can stabilize and protect the phosphorescence bio-probes but impede their intravenous delivery across biological barriers. Here, a new class of biocompatible rhenium (ReI ) diimine carbonyl complexes is developed, which can efficaciously permeate normal vessel walls and then functionalize the extravascular collagen matrixes as in situ oxygen sensor. Without protective agents, ReI -diimine complex already exhibits excellent emission yield (34%, λem = 583 nm) and large two-photon absorption cross-sections (σ2 = 300 GM @ 800 nm) in water (pH 7.4). After extravasation, remarkably, the collagen-bound probes further enhanced their excitation efficiency by increasing the deoxygenated lifetime from 4.0 to 7.5 µs, paving a way to visualize tumor hypoxia and tissue ischemia in vivo. The post-extravasation functionalization of extracellular matrixes demonstrates a new methodology for biomaterial-empowered phosphorescence sensing and imaging.

Keywords: ReI diimine carbonyl complexes; phosphorescence lifetime imaging microscopy; phosphorescent oxygen sensors; tissue ischemia; tumor hypoxia; two-photon phosphorescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Vessels / diagnostic imaging*
  • Blood Vessels / drug effects
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Collagen / genetics
  • Collagen / metabolism*
  • Humans
  • Iridium / pharmacology
  • Luminescent Agents / pharmacology*
  • Microscopy, Confocal
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Oxygen / metabolism*
  • Photons
  • Rhenium / chemistry
  • Tumor Hypoxia / genetics
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics

Substances

  • Luminescent Agents
  • Iridium
  • Rhenium
  • Collagen
  • Oxygen