Chiral NIR-II fluorescent Ag₂S quantum dots with stereospecific biological interactions and tumor accumulation behaviors

Near-infrared II (NIR-II) fluorescent nanoprobes hold great potential for biomedical applications. Elucidating the relationship between surface properties of NIR-II nanoprobes and their biological behaviors is particularly important for future probe design and their performance optimization. Despite the rapid development of NIR-II nanoprobes, the distinct role of surface chirality on their biological fates has rarely been exploited. Herein, chiral NIR-II fluorescent Ag₂S quantum dots (QDs) are synthesized to investigate the relationship between their chirality and biological functions at both in vitro and in vivo levels. D-/L-Ag₂S QDs exhibit significant differences on their interactions with serum proteins, which further affect the cellular uptake. As a result, D-Ag₂S QDs can be internalized with higher efficiency (over 2-fold) than that of L-Ag₂S QDs. Moreover, in vivo studies reveal that the chirality determines the primary localization of these chiral QDs, where a more efficient renal elimination of D-Ag₂S QDs was observed than that of L-Ag₂S QDs. Importantly, D-Ag₂S QDs show preferential accumulation in tumor region than that of L-Ag₂S QDs in orthotopic kidney tumor model, which points out a new avenue of enhancing targeting capabilities of nanoprobes by engineering their surface chirality.