Liposomal structure tuned J-aggregated ICG as enhanced NIR-II imaging nanoprobe

• A near-infrared II imaging probe based on the liposomal structure tuned J-aggregated indocyanine has been developed. • Molecular dynamics simulation shows that J-aggregated indocyanine is modulated by the interaction with liposomal structure. • Experimental results show that J-aggregated indocyanine is endowed with near-infrared II enhancement capability. • The J-aggregated indocyanine liposomes show specific near-infrared II imaging for lymph node metastatic tumors in mice. Although near-infrared II (NIR-II) fluorescence imaging (FI) for accurate and noninvasive diagnosis of solid cancer has been developed as one of the crucial methods for formulating appropriate clinical treatment strategies, it is still hindered by the limited availability of NIR-II nanoprobes. In this study, we aim to develop high performance and biocompatible NIR-II probes based on novel mechanism of the aggregation of NIR fluorephores. Using domain effect of liposomal nanostructures, the J-aggregated state of indocyanine (ICG) NIR-II nanoprobes were elaborately fabricated. Combined with molecular dynamics simulation, the molecular mechanism of the formation of J-aggregated state of ICG molecules was discovered. Results show that the engineered J-aggregated state of ICG with a concentration below 50 μg/mL can fine tune ICG interactions instead of ICG-intermolecular interactions within liposomal structure. The rational designed ICG cationic liposomes (IJA-CLPs) show 3-fold enhancement in NIR-II intensity compared to the conventional ICG liposomes (ICG-CLPs). Furthermore, for a mouse model of mammary tumors with lymph node metastasis, IF7 peptide-modified IJA-CLPs (IF7-IJA-CLPs) can successfully discriminate tumor cell-metastasized lymph nodes with more than 4-fold fluorescence signal improvement. Thus, it is expected to provide a new avenue for designing NIR-II fluorescent probes for enriching the clinical NIR imaging applications.