Ultrasensitive In Vivo Imaging of Adoptive Immune Cell Distribution and Expansion Using Second Near-Infrared Conjugated Oligoelectrolyte Probes

  • Research (Wash D C). 2026 Jun 26:9:1342. doi: 10.34133/research.1342.
Shengnan Yuan  1  2 ,  Qingshuang Li  1  2 ,  Xi Kang  3 ,  Yingying Meng  4 ,  Pengke Liu  4 ,  Pengfei Zhang  1  2 ,  Jin Zhang  1  2 ,  Dehong Hu  1  2 ,  Duyang Gao  1  2 ,  Caoyun Ju  5 ,  Xiuqi Li  5 ,  Can Zhang  5 ,  Hairong Zheng  1  2 ,  Nuernisha Alifu  6 ,  Cheng Zhou  4 ,  Zonghai Sheng  1  2
Affiliations
  • 1. Research Center for Advanced Detection Materials and Medical Imaging Devices, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P. R. China.
  • 2. State Key Laboratory of Biomedical Imaging Science and System, Shenzhen 518055, P. R. China.
  • 3. Translation Innovation Center, Shenzhen Bay Lab, Shenzhen 518132, P. R. China.
  • 4. Institute of Polymer Optoelectronic Materials and Devices, Guangdong Basic Research Center of Excellence for Energy & Information Polymer Materials, State Key Laboratory of Luminescent Materials and Devices, School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, P. R. China.
  • 5. State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P. R. China.
  • 6. State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, School of Medical Engineering and Technology & Technology Innovation and Translational Service Center, Xinjiang Medical University, Urumqi 830054, P. R. China.
PMID: 42369837 DOI: 10.34133/research.1342
Abstract

Monitoring adoptive cell therapy in solid tumors is critical for evaluating treatment efficacy and guiding clinical medication but is also hindered by poor sensitivity, high background signals, and disruptions of therapeutic functions in existing techniques. In this study, a membrane-mimicking conjugated oligoelectrolyte with second near-infrared (NIR-II) fluorescence, conjugated oligoelectrolytes-benzobisthiadiazole (COE-BBT), is applied for the first time to label and track chimeric antigen receptor (CAR)-engineered natural killer (CAR-NK) cells and T (CAR-T) cells in vivo. COE-BBT stably embeds in lipid bilayers through combined electrostatic and hydrophobic interactions, resists membrane crossing, and supports long-lasting labeling with a lighting-up property. The optimized labeling approach achieves high sensitivity, enabling the detection of as few as ~20 labeled cells in vitro and ~50 cells in vivo under NIR-II imaging. In orthotopic and subcutaneous glioma models, NIR-II fluorescence imaging enables continuous tracking of CAR-NK and CAR-T cell proliferation, migration, tumor homing, and blood-brain barrier penetration for up to 14 d posttransfer as the fluorescence signal is enhanced during proliferation, without compromising cell viability or cytotoxic function. The COE-BBT probe also exhibits favorable biosafety, underscoring its translational potential as a robust imaging strategy to improve solid tumor adoptive cell therapy monitoring and clinical guidance of therapeutic dosing.

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