Genipin Cross-Linked Blue Lys-Fa Nanoparticles For Targeted Visible Glioma Cell Staining And Drug Delivery

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY(2021)

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摘要
Design and fabrication of multifunctional nano-carrier is a promising tool in the field of nanomedicine for glioma theranostics. In this study, blue color nanoparticles with targeted tumor cell staining and drug delivery capabilities were simply fabricated by crosslinking lysine (Lys) and lysine-folic acid (Lys-FA) mixture with genipin as the crosslinking agent through a reversed microemulsion method. Doxorubicin (DOX) as the model drug was loaded through electrostatic interaction. The nanoparticles before (Lys-FA NPs) and after (Lys-FA/DOX NPs) loading of DOX were characterized by ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared spectroscopy (FTIR), dynamic laser light scattering (DLS), transmission electron microscopy (TEM), and fluorescence spectroscopy. Ultimately, the glioma cell staining ability of Lys-FA NPs and cytotoxicity of Lys-FA/DOX NPs were tested in vitro. The results showed that the particle size of Lys-FA NPs can be tuned by adjusting the ratio of Lys to Lys-FA simply. The Lys-FA NPs exhibited dark blue and the blue color is stable under different pH values and temperatures. The feature makes the staining glioma cell pellets visible to naked-eyes. The model drug DOX was loaded on Lys-FA NPs indicated by the increase of size and zeta potential, and change of optical properties. The DOX loaded on the Lys-FA NPs can be sustainedly released, other than burst release. Encouragingly, the Lys-FA NPs can deliver DOX into cells and dramatically reduce cell viability, as proved by U87 cell cytotoxicity analysis and confocal fluorescence imaging. In addition, the Lys-FA NPs (<= 2.5 mg mL(-1)) are nontoxic to CHO cells. In a short, the blue color Lys-FA NPs can visibly stain glioma cell pellets and deliver DOX into glioma cells, which can potentially be applied as a multifunctional nanocarrier for tumor imaging and drug delivery.
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关键词
Multifunctional nanoparticles, Tumor cell staining, Targeted drug delivery, Genipin-crosslink, Glioblastoma
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