Non-invasive tracking of hydrogel degradation using upconversion nanoparticles.

Tracking the distribution and degradation of hydrogels in vivo is important for various applications including tissue engineering and drug delivery. Among various imaging modalities, fluorescence imaging has attracted intensive attention due to their high sensitivity, low cost and easy operation. Particularly, upconversion nanoparticles (UCNPs) that emit visible lights upon near-infrared (NIR) light excitation as tracking probes are promising in deciphering the fate of hydrogels after transplantation. Herein, we reported a facile and non-invasive in vivo hydrogel tracking method using UCNPs, where the degradation of hydrogels was determined using the decrease in fluorescence intensity from the UCNPs encapsulated in the hydrogels. We found that the change in the fluorescence intensity from the UCNPs was well consistent with that of the fluorescein isothiocyanate (FITC) covalently conjugated to hydrogels and also with the weight change of the hydrogels, suggesting the accuracy of the UCNPs in tracking the degradation of hydrogels. Furthermore, the in vivo fluorescence signals were only observed from the UCNPs instead of FITC after implantation for 7days due to the deep tissue penetration of UCNPs, demonstrating the capability of UCNPs in longitudinal, consecutive and non-invasive monitoring the in vivo degradation of hydrogels without causing any damage to the major organs (heart, lung, liver and kidney) of model rats. This study thus paves the way for monitoring the in vivo behaviors of biomimetic materials via deep tissue imaging with great clinical translation potentials.

STATEMENT OF SIGNIFICANCE: Long-term noninvasive in vivo tracking of the distribution and degradation of biodegradable hydrogels using fluorescent probes is important in tissue regeneration and drug delivery. Unlike the widely used fluorescent dyes and quantum dots (QDs) that suffer from photobleaching and undesired toxicity, upconversion nanoparticles (UCNPs) with high stability, deep tissue penetration as tracking probes are promising in deciphering the fate of hydrogels after transplantation. Herein, we reported a noninvasive in vivo hydrogel tracking method using UCNPs and found that the fluorescence intensity change from the UCNPs was well consistent with the weight change of the hydrogels, suggesting the accuracy of UCNPs in tracking hydrogel degradation. This study provides inspirations on developing advanced NIR light regulated probes with great clinical translation potentials.