Chiral Triple-Helix β-Glucan Self-Assembled Nanoparticles For Drug Delivery

Aim:Yeast-derived β-glucan,a glucan with a chiral triple helical structure,has several advantages including high biocompatibility,abundant sources,and unique immunomodulatory activity,which earns it a good application prospect in the field of biomedicine.This study focuses on constructing a drug carrier system by regulating the self-assembly process of the β-glucan,and then to study the performance and biological functions of the carrier.Our research provides a new idea and method for the synthesis and construction of new drug carrier system.Methods:β-glucan molecules with different chain lengths were extracted from yeast Saccharomyces cerevisiae and thereafter modified.In a conformation transition process,these β-glucan molecules were then self-assembled with anti-cancer drug Doxorubicin(DOX)and anti-inflammatory drug Berberine(BER)into nanoparticles to construct drug delivery systems,respectively.The chiral interactions between the drug and carriers were revealed by circular dichroism spectra,ultraviolet and visible spectrum,fourier transform infrared spectroscopy,dynamic light scattering and transmission electron microscope.The immune-potentiation properties of modified β-glucan nanoparticles were evaluated by analysis of the m RNA expression in RAW264.7 cell model.Further,the antitumor efficacy of the β-glucan/DOX against the human breast cancer were studied in MCF-7 cell model by cellular uptake and cytotoxicity experiments.The anti-inflammatory effect of the β-glucan/BER drug carrier was evaluated through lipopolysaccharide(LPS)-induced inflammation model on RAW264.7 macrophage and dextran sodium sulfate(DSS)-induced ulcerative colitis model on C57BL/6 mice.Results:β-glucan/DOX nanoparticles can activate macrophages to produce immune enhancing cytokines(IL-1β,IL-6,TNF-α,IFN-γ).A special chirality of the carriers in diameter of 50～160 nm can also associate with higher drug loading ability of 13.9% ～38.2% and p H-sensitive release with a change of p H from 7.4 to 5.0.Cellular uptake and cytotoxicity experiments also prove that the chiral-active β-glucan nanoparticles can be used in anti-cancer nanomedicine.β-glucan/BER nanoparticle,with nanoparticle size ranging from 80 nm to120 nm,exhibits a higher encapsulation rate around 28.4%.On the LPS-induced RAW264.7 macrophage inflammation model,the drug carrier can significantly promote the uptake of BER by RAW264.7 cells.Further,RT-q PCR experiments demonstrate that it can significantly diminish the expression of m RNA of IL-1β,IL-6 and COX-2;Western Blot experiments reveal that it can inhibit inflammation-related signal pathways including NF-κB,NLRP3,COX-2;ELISA experiments and NO test experiments display that the β-glucan/BER drug carrier can reduce the secretion of inflammatory factor(IL-1β,IL-6)and the excretion of inflammation-related chemicals(NO).In the mouse ulcerative colitis(UC)model,the β-glucan/BER drug carrier can effectively alleviate the occurrence and progression of colitis,mainly in that the drug carrier can relieve several symptoms caused by DSS-induced colitis.Conclusion:This work demonstrates that β-glucan nanoparticles with special chiral feature which leading to strong immunoregulation ability and high drug loading efficiency can be developed as a novel type of nanomedicine for anti-cancer and anti-inflammatory treatment.