Shape-Tunable Nanocellulose-Based Fluorescent Nanoprobes for In Vivo NIR-II Fluorescence Imaging

Elongated nanoparticles offer distinct advantages over spherical nanoparticles in bioimaging applications, particularly due to their extended in vivo retention time. In this study, we for the first time demonstrate the utilization of cellulose nanocrystals (CNCs) as template carriers along with their surface aldehyde functional groups, via in situ growth and surface covalent bonding, to construct near-infrared II (NIR-II) fluorescent nanoprobes with finely tunable aspect ratios ranging from 1.07 to 18.60. These nanoprobes exhibit excellent colloidal stability, biocompatibility, and intense NIR-II absorption/emission properties, making them highly suitable for deep-tissue fluorescence imaging. Systematic in vivo investigations reveal a clear aspect ratio-dependent biodistribution behavior: the small‑sized rod‑shaped nanoprobes exhibit superior tumor retention effect, while the approximately spherical smaller nanoprobes possess rapid tumor penetration capability. Our work not only elucidates the critical role of nanoparticle geometry in modulating biodistribution and tumor targeting efficiency but also establishes a versatile CNC-based imaging platform with high translational potential for vascular and oncological diagnostics. These findings provide valuable design principles for developing next-generation NIR fluorescent probes tailored for precision biomedical imaging.