| 5-fluorouracil?5-FU?is one of the main anti-tumor drug in clinic.However,the application in clinic was limited due to its high toxicity and side effect,rapid metabolism,and short elimination half-life.As a novel delivery system,the Drug Delivery Systems based on nanoparticles has many advantages,such as stimuli responsive,targeting therapy,imaging and tracking drugs,thus it has attracted great attentions in anti-tumor field.Objective:In this study,we chose 5-FU as a model drug,carbon dots as a drug carrier,designed and prepared a multifunctional drug delivery system with pH-triggered drug release.It lay a foundation for the development and design of nanocarrier drug delivery systems of 5-FU.Methods:?1?Glucose as carbon source,NPHCDs were generated via the spontaneous heat produced from the acid-base neutralization.To investigated the properties of NPHCDs,it could be seen from the transmission electron microscopy?TEM?,UV-vis absorption spectrum,photoluminescence?PL?spectrum,X-ray photoelectron spectroscopy?XPS?,quantum yield?QY?,and the safety evaluation.?2?NPHCDs@5-FU were obtained by specific electrostatic interactions,and using UV-vis absorption spectrum and Zeta potential to verify the successful synthesis of NPHCDs@5-FU,HPLC was calculated the drug loading ratio,the physical placement stability of NPHCDs was investigated,and the drug release characteristics was evaluated using dialysis technique by simulation of normal and tumor cell environment.?3?In vitro,the antitumor activity of 5-FU and NPHCDs@5-FU were explored by a model of SGC-7901 cells.The MTT assay was used to evaluate cytotoxicity,the cellular uptake and apoptosis of NPHCDs@5-FU in SGC-7901 cells were evaluated using confocal microscopy and flow cytometry.?4?The intravenous administration of 5-FU and NPHCDs@5-FU complexes to SD rats was investigated,and the main pharmacokinetic parameters were compared.In vivo anti-tumor efficacy and safety study of 5-FU and NPHCDs@5-FU was studied on SGC-7901melanoma-bearing Balb/c nude mice.Results:?1?The NPHCDs were obtained had many excellent properties,such as good water solubility,uniform particle distribution,hollow structure,the particle size was5.36±0.28 nm,the solution of NPHCDs emitted a strong blue light under irradiation with a 365 nm UV lamp,UV-vis spectrum and FTIR spectrum showed that NPHCDs had unique PL properties with a quantum yield of 16.23%,and the level of photoluminescence is stable in different medium.What's more,the low cell toxicity and good bio-compatibility of NPHCDs indicated that it could be used as a carrier for drug delivery systems,and has good potential and applications in biological nano-particle drug delivery system.?2?The evaluation of NPHCDs@5-FU showed that the cationic anticancer drug 5-FU effectively binds onto the negatively charged NPHCDs through electrostatic interactions to form NPHCDs@5-FU,and the 5-FU loading ratio was 31.25%.The NPHCDs@5-FU were stabilized at 4?and room temperature.Furthermore,the release of 5-FU from the NPHCDs@5-FU is faster in acidic pH media than in neutral pH environments,as in the tumor micro-environment.?3?Compared with free 5-FU,NPHCDs@5-FU had more obvious effect on inhibiting SGC-7901 cells and promoting their apoptosis.?4?Pharmacokinetic studies in SD rats showed that NPHCDs@5-FU improved the progress of 5-FU with a obvious increase in pharmacokinetic parameters,such as AUC?0-t??2.1 fold?,AUC?0-???2.2 fold?,t1/2?2.5fold?,and Cmax?1.4 fold?,compared with free 5-FU.The results of anti-tumor research showed that NPHCDs@5-FU could significantly reduce the tumor volume and weight,compared with free 5-FU.Therefore,the NPHCDs@5-FU had the effective in vivo anti-tumor effect and good bio-safety properties.Conclusion:In this study,the NPHCDs has many excellent properties,such as:good water solubility,hollow structure,small particle,low cell toxicity and good biocompatibility.The NPHCDs@5-FU has high drug loading ratio,pH responsive ability,and it can effectively improve the anti-tumor activity in vitro and in vivo. |
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