Dual-Interface Hierarchical Assembly of Asymmetric ICG-Lipid Conjugates Enables Finite J-type Aggregation and

Hanbin Xu1, Jian Wu2, Jinying Qin1

  • 1Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.

Nano Letters
|March 30, 2026
PubMed

Aggregation-induced quenching severely limits the imaging properties of indocyanine green (ICG), despite its FDA approval and its emission in the near-infrared II (NIR-II) region. Herein, we introduce a dual-interface assembly strategy that orchestrates the sequential assembly of asymmetric ICG-lipid conjugates at lipid and liposome-protein interfaces to achieve two-stage NIR-II fluorescence enhancement. The ICG-sphingosine conjugates without sulfonate groups (ICG-C-Sp) form finite, weakly coupled J-type aggregates within lipid bilayers, producing markedly enhanced NIR-II fluorescence. Upon serum protein adsorption, H-aggregation is further suppressed and the finite J-type component is reinforced, yielding a secondary fluorescence enhancement. This strategy generates bright NIR-II emission beyond 1300 nm and prolongs circulation. After M2pep modification, the nanoprobes enable high-contrast imaging of subcutaneous and orthotopic bladder tumors. Notably, the nanoprobes can detect ultrasmall lung metastatic tumors and human bladder cancer in ex vivo tissues. This sequential assembly strategy enables the development of clinically translatable NIR-II fluorescent probes.