Manipulating emitting properties of fluorescent dyes plays a critical role in various fields such as light emitting materials, living cell imaging, and phototheranostics [1]. In particular, supramolecular strategies, such as complexation-induced quenching, aggregation-induced emission, have attracted ever-growing attention [2]. Near-infrared (NIR) probes have been demonstrated to possess advantages of slight photo-damage and low interference of autofluorescence for organelle-targeted cell imaging [3]. However, NIR fluorescent supramolecular assemblies were rarely reported owing to the lack of NIR dyes as well as the aggregation-caused quenching effect.

Recently, Liu and coworkers from Nankai University reported a supramolecular assembly with NIR emission for lysosometargeted cell imaging [4]. This two-step approach took advantages of the complexation of both cucurbituril and amphiphilic calixarene (Fig. 1). In the first step, encapsulation of cucurbit[8] uril (CB[8]) gives rise to J-aggregation of an anthracyl pyridinium derivative (ENDT), accompanied with emission enhancement and red-shift. In the second step, the fluorescence of the ENDT/CB[8] complex was further enhanced through lower-rim dodecylmodified sulfonatocalix[4]arene (SC4AD) induced aggregation.

A sled n:n motif of the ENDT/CB[8] complexation was determined through a 54 nm red-shift of absorbance and ¹H NMR and 2D NOESY spectra. The ENDT/CB[8] complex formed nanorods and adding SC4AD induced the formation of spherical nanoparticles with NIR fluorescence further enhanced. Two stage fluorescence enhancements are responsible for restricting the rotation of single bonds, avoiding the π–π stacking and providing a hydrophobic environment for ENDT.

Cell imaging was validated in living cell through confocal laser scanning microscopy after treating with the ternary ENDT/CB[8]/SC4AD assembly for 4 h. Subcellular distribution and cytotoxicity were also studied. The in vitro results indicate that the ternary assembly had the capability of selectively imaging lysosome and negligible cytotoxicity in the concentration of fluorescence imaging.

In summary, a self-assembled NIR-fluorescent nanoparticle for lysosome-targeted NIR imaging in living cells was constructed by Liu and coworkers [4]. Much of supramolecular chemistry has sprung from developments of molecular recognition and selfassembly of macrocycles since 1960s. On demand of precision medicine, two interdisciplines derived from supramolecular chemistry, supramolecular biomedical materials and supramolecular medicine, emerged in recent years. Meanwhile, they represent one aspect of functional supramolecular systems, that is, biomedical applications. Macrocycles have also played a crucial role in these two newly developing fields. To be envisaged, such a hierarchical strategy would pave an alternative avenue to construct smart biomedical materials by integrating two or more kinds of complementary macrocycles into one supramolecular ensemble.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos. 51873090 and 21672112), the Fundamental Research Funds for the Central Universities and Program of Tianjin Young Talents, which are gratefully acknowledged.