Dynamic tracing using ultra-bright labeling and multi-photon microscopy identifies endothelial uptake of poloxamer 188 coated poly(lactic-co-glycolic acid) nano-carriers in vivo

The potential of poly(lactic-co-glycolic acid) (PLGA) to design nanoparticles (NPs) and target the central nervous system remains to be exploited. In the current study we designed fluorescent 70-nm PLGA NPs, loaded with bulky fluorophores, thereby making them significantly brighter than quantum dots in single-particle fluorescence measurements. The high brightness of NPs enabled their visualization by intravital real-time 2-photon microscopy. Subsequently, we found that PLGA NPs coated with pluronic F-68 circulated in the blood substantially longer than uncoated NPs and were taken up by cerebro-vascular endothelial cells. Additionally, confocal microscopy revealed that coated PLGA NPs were present in late endothelial endosomes of cerebral vessels within 1 h after systemic injection and were more readily taken up by endothelial cells in peripheral organs. The combination of ultra-bright NPs and in vivo imaging may thus represent a promising approach to reduce the gap between development and clinical application of nanoparticle-based drug carriers.(c) 2021 Elsevier Inc. All rights reserved.

Automated summary

The study designed fluorescent 70-nm PLGA NPs with high brightness for visualization by intravital real-time 2-photon microscopy and found that PLGA NPs coated with pluronic F-68 circulated in the blood longer and were taken up by cerebro-vascular endothelial cells. The combination of ultra-bright NPs and in vivo imaging may provide a promising approach to bridge the gap between development and clinical application of nanoparticle-based drug carriers.