Remote and reversible control of in vivo bacteria clustering by NIR-driven multivalent upconverting nanosystems

Achieving remote and reversible control of bacterial cell-cell interactions associated with interference with pathological processes in living systems remains a challenge owing to the complexity of the in vivo microenvironment and the lack of regulation systems. We present, for the first time, the development of a versatile platform to achieve NIR-driven reversible bacterial clustering both in vitro and in vivo. This platform consisted of β-CD modified UCNP (UCNP-CD) and photochromic azobenzene glycoconjugates (azo-man), which could dynamically display d-mannose bioactive ligands. Specifically, by virtue of the noncovalent yet strong multivalent interactions between bacteria and nanosystems, robust bacterial clusters could be formed even in vivo within 1 h. Upon NIR stimulation, the upconverted emissions from UCNPs triggered the continuous isomerization of azo-man, leading to dissociation of the nanosystems and dispersion of bacterial clusters. Moreover, in vivo pathogenic infection process could be interfered with the NIR-switched bacterial agglutination. Most importantly, the noninvasive and deep-tissue-penetrating nature of NIR made it possible for dynamically regulation of cellular interactions with minimized influence to both normal cells and nature bacteria flora. This strategy would bring new perspectives for anti-virulence therapeutics and in-depth investigations of specific physiological phenomena.