Abstract
Nanoparticles hold great promise as drug carriers for the central nervous system (CNS), however, knowledge about their biodistribution within the CNS remains fragmentary. To overcome this, we used poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer approved for the use in humans, to prepare nanocarriers and loaded them with bulky fluorophores. Thereby, we increased single particle fluorescence by up to 55-fold as compared to quantum dots. As a consequence, 70 nm PLGA nanocarriers were visualized by intravital real-time 2-photon microscopy, demonstrating that coating with pluronic F-68 (PF-68) significantly increased the circulation time of PLGA nanoparticles in the blood and facilitated their uptake by cerebral endothelial cells in mice. Using a novel in vivo imaging protocol we unambiguously distinguished, by confocal microscopy, nanoparticles’ fluorescence from tissue auto-fluorescence and demonstrated how PF-68 coated PLGA NPs were taken up into late endothelial lysosomes within 1 hour. In summary, by increasing the brightness of clinically approved PLGA nanocarriers to a level which allowed in vivo detection, we were able to demonstrate that PF-68 shifts the uptake of individual particles from macrophages towards endothelial cells. Our novel technological approach significantly improves the ability to evaluate tissue targeting of nanoscale drug-delivery systems in living organisms, thereby remarkably reducing the gap between their development and clinical translation.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
the figures quality and as well as explanations about findings. We also add one supplementary figure regarding the spectra of nanocarriers.