Bio-inspired indocyanine green supramolecular assemblies for high-contrast NIR-II imaging and cooperative dual-targeting of bladder cancer.

Authors

Hanbin Xu, Jian Wu, Yongke Bai, Jinying Qin, Rui Sun, Zhong'an Li, Kun Tang, Yijing Liu, Jintao Zhu

Published in

Biomaterials. Volume 335. Pages 124397. Jun 19, 2026. Epub Jun 19, 2026.

Abstract

Developing supramolecular strategies that simultaneously regulate photophysical behavior and enable efficient biological targeting of indocyanine green (ICG) remains a major challenge for clinically compatible near-infrared region II (NIR-II) probes, as aggregation-caused quenching and ineffective tumor targeting severely limit their diagnostic potential. Here, inspired by natural light-harvesting complexes that utilize cooperative supramolecular interactions and spatial confinement to regulate chromophore behavior, we report a multi-interaction supramolecular engineering strategy to construct an ICG complex (CMPI) that simultaneously enhances photophysical performance and enables microenvironment-responsive cooperative dual targeting. A β-cyclodextrin-M2pep-aconitic acid carrier establishes a synergistic network of host-guest inclusion, electrostatic attraction, hydrogen bonding, and steric effects, which suppresses aggregation and stabilizes ICG within a spatially confined environment, thereby markedly enhancing NIR-II brightness (∼4-fold) and quantum yield (∼1.9%). In acidic tumor microenvironments, CMPI undergoes rapid charge reversal and in situ assembly, thereby amplifying the targeting of M2-like tumor-associated macrophages. Finally, CMPI prolongs circulation (half-life t_1/2 ∼14.1 min), preserves the clearance ability of ICG, and achieves a tumor-to-normal ratio of ∼11.1, enabling high-contrast NIR-II imaging and fluorescence-guided surgery across multiple bladder tumor models, including sensitive detection of sub-millimeter lesions. This strategy provides a clinically compatible supramolecular approach for simultaneously enhancing the photophysical properties and targeting of FDA-approved dyes.

PMID:
42323929
Bibliographic data and abstract were imported from PubMed on 22 Jun 2026.

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