ABSTRACT
During fluorescence-guided cancer surgery, ultra-pH sensitive (UPS) fluorescent nanoprobes has multiple advantages such as real-time imaging procedures, ultra-high imaging sensitivity as well as broad tumor detection specificity. UPS nanoprobes stay at "OFF" state at higher pH and turn into "ON" state at lower pH with emission of strong fluorescence. Moreover, the transition pH points (transition pH point, pHt) can be precisely controlled by structural-based strategy. One of the previously-reported UPS nanoprobes showed good imaging effect. However, it is still not clear about the effect of pHt on cancer imaging efficiency of UPS nanoprobes and to further identify the optimal UPS. In this study, we synthesized a series of UPS nanoprobes with pHt at 4.5, 6.2, 6.6, 7.8 by adjusting the hydrophobic blocks of UPS polymers. Each nanoprobe showed excellent stability in "OFF" state by dynamic light scattering and uniform morphology observed by transmission electron microscopy. In vitro imaging characterized the ultra-pH sensitive fluorescence transition of each probe. In vivo imaging results identified two UPS nanoprobes (NP-6.2 and NP-6.6) with superior tumor imaging effect. All animal experiments in this study were approved by the Animal Ethics Committee of Peking University Health Science Center and were strictly followed by the welfare regulations of laboratory animals of Peking University Health Science Center. Therefore, this study has explored the effect of pHt on the cancer imaging efficiency of UPS nanoprobes and provides a new idea for design of the other cancer microenvironment-responsive polymers.
ABSTRACT
This study was designed to investigate the impacts of particle shape of micelles on cell uptake and tumor imaging applications. We designed and synthesized an ultra-pH sensitive PEG-iPDPA diblock polymer, and prepared it into wormlike micelles and spherical micelles by thin-film dispersion method and modified solvent evaporation method, respectively. Firstly, the pH responsiveness of two kinds of micelles was investigated in vitro. Both forms of micelles responded to pH sensitively, and each of them could reach 100 times of ON/OFF fold after conjugated with BDP fluorescent probe. Moreover, the cellular uptake of two forms of micelles depended on the concentration and incubation time. However, the amount of cellular uptake of spherical micelles was much higher than that of the wormlike micelles, which proved that the shape of nanoparticles had a great influence on the cellular uptake. The results of in vivo imaging revealed that the spherical micelles had a better tumor accumulation as well as tumor imaging outcomes. Finally, the biosafety of micelles was tested by MTT assay and H&E staining, which indicated that none of the two kinds of micelles had obvious toxicity. Collectively, these results suggest that the spherical micelles could be a better carrier compared with wormlike micelles in terms of cellular uptake, tumor accumulation and tumor detection.