2. Academic Validation
  3. [Ru(dpp)3]Cl2-Embedded Oxygen Nano Polymeric Sensors: A Promising Tool for Monitoring Intracellular and Intratumoral Oxygen Gradients with High Quantum Yield and Long Lifetime

[Ru(dpp)3]Cl2-Embedded Oxygen Nano Polymeric Sensors: A Promising Tool for Monitoring Intracellular and Intratumoral Oxygen Gradients with High Quantum Yield and Long Lifetime

  • Small. 2024 Apr;20(17):e2307955. doi: 10.1002/smll.202307955.
Ashish Kumar 1,  Venkanagouda S Goudar 1,  Bishal Kumar Nahak 1,  Ping-Hsun Tsai 2,  Hao-Wu Lin 2,  Fan-Gang Tseng 1 3 4 5 6
Affiliations

Affiliations

  • 1 Department of Engineering and System Science, National Tsing Hua University, Hsinchu, 300044, Taiwan ROC.
  • 2 Department of Material Science and Engineering, National Tsing Hua University, Hsinchu, 300044, Taiwan ROC.
  • 3 Institute of Nano Engineering and Microsystems, National Tsing Hua University, Hsinchu, 300044, Taiwan ROC.
  • 4 Department of Chemistry, National Tsing Hua University, Hsinchu, 300044, Taiwan ROC.
  • 5 Research Center for Applied Sciences, Academia Sinica, Taipei, 115201, Taiwan ROC.
  • 6 Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, 300044, Taiwan ROC.
PMID: 38148312 DOI: 10.1002/smll.202307955
Abstract

Unraveling the intricacies between oxygen dynamics and cellular processes in the tumor microenvironment (TME) hinges upon precise monitoring of intracellular and intratumoral oxygen levels, which holds paramount significance. The majority of these reported oxygen nanoprobes suffer compromised lifetime and quantum yield when exposed to the robust ROS activities prevalent in TME, limiting their prolonged in vitro usability. Herein, the ruthenium-embedded oxygen nano polymeric sensor (Ru-ONPS) is proposed for precise oxygen gradient monitoring within the cellular environment and TME. Ru-ONPS (≈64±7 nm) incorporates [Ru(dpp)3]Cl2 dye into F-127 and crosslinks it with urea and paraformaldehyde, ensuring a prolonged lifetime (5.4 µs), high quantum yield (66.65 ± 2.43% in N2 and 49.80 ± 3.14% in O2), superior photostability (>30 min), and excellent stability in diverse environmental conditions. Based on the Stern-Volmer plot, the Ru-ONPS shows complete linearity for a wide dynamic range (0-23 mg L-1), with a detection limit of 10 µg mL-1. Confocal imaging reveals Ru-ONPS cellular uptake and intratumoral distribution. After 72 h, HCT-8 cells show 5.20±1.03% oxygen levels, while NIH3T3 cells have 7.07±1.90%. Co-culture spheroids display declining oxygen levels of 17.90±0.88%, 10.90±0.88%, and 5.10±1.18%, at 48, 120, and 216 h, respectively. Ru-ONPS advances cellular oxygen measurement and facilitates hypoxia-dependent metastatic research and therapeutic target identification.

Keywords

cellular uptake; fluorescence imaging; hypoxia; oxygen gradients; ruthenium‐embedded oxygen nano polymeric sensor (Ru‐ONPS); tumor microenvironment.

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