负载姜黄素的氧化锌纳米粒的制备及抗癌评价
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摘要
氧化锌纳米粒(ZnO NPs)的化学稳定性、生物相容性和高载药性能使其有望成为一种新型药物传递载体.研究拟开发一种经N-乙酰-L-半胱氨酸(NAC)封端并表面功能化的ZnO NPs,作为抗癌药物姜黄素的给药系统.在含NAC的溶液中,用ZnCl_2和NaOH成功制备NAC封端ZnO NPs(ZnO-NAC NPs),然后将姜黄素共价结合到纳米粒表面,制得载药纳米粒(ZnO-NAC-Cur NPs).用X射线衍射法、傅里叶变换红外光谱法、透射电镜、扫描电镜(SEM)和动态光散射法进行表征.结果表明,ZnO-NAC-Cur NPs呈近球形,均匀分散,平均粒径约为70 nm. ZnO-NAC-Cur NPs几乎无溶血性.此外,用B16F10鼠黑色素瘤细胞进行MTT细胞毒试验,结果表明,IC_(50)值从17.23μg·mL~(-1)(游离姜黄素)降到8.78μg·mL~(-1)(ZnO-NAC-Cur NPs).该结果表明,载药纳米粒的抗癌活性增强.
The chemical stability, good biocompatibility and high drug loading capacity of zinc oxide nanoparticles(ZnO NPs) and their biomedical potentials make them promising candidates for drug delivery. The aim of this study is to develop and assess a simple procedure for capping and surface functionalization of ZnO NPs by N-acetyl-L-cysteine(NAC) for anticancer curcumin(Cur) delivery. NAC capped ZnO NPs(ZnO-NAC NPs)have been successfully made by using ZnCl_2 and NaOH in the presence of NAC. Curcumin has been conjugated covalently to the surface of as-synthesized ZnO-NAC NPs. To characterize the synthesized conjugate product(ZnO-NAC-Cur NPs), X-ray diffraction(XRD), Fourier Transform Infrared spectroscopy(FTIR), transmission electron microscopy(TEM), scanning electron microscopy(SEM), and dynamic light scattering method(DLS)have been used. The results indicate that the ZnO-NAC-Cur NPs exhibit near-spherical morphology and uniform dispersion with an average diameter of ～70 nm. The hemolysis assay shows that ZnO-NAC-Cur NPs has almost no hemolytic activity. In addition, MTT cytotoxicity assessment on B16F10 murine melanoma cells present a drop of IC_(50) values from 17.23 μg·mL~(-1)(free curcumin) to 8.78 μg·mL~(-1)(ZnO-NAC-Cur NPs). This result shows an augmented cancer-inhibitory effect of nanoconjugate complex. In conclusion, the novel ZnO-NAC-Cur NPs could be explored for new therapeutic endeavors.
The chemical stability, good biocompatibility and high drug loading capacity of zinc oxide nanoparticles(ZnO NPs) and their biomedical potentials make them promising candidates for drug delivery. The aim of this study is to develop and assess a simple procedure for capping and surface functionalization of ZnO NPs by N-acetyl-L-cysteine(NAC) for anticancer curcumin(Cur) delivery. NAC capped ZnO NPs(ZnO-NAC NPs)have been successfully made by using ZnCl_2 and NaOH in the presence of NAC. Curcumin has been conjugated covalently to the surface of as-synthesized ZnO-NAC NPs. To characterize the synthesized conjugate product(ZnO-NAC-Cur NPs), X-ray diffraction(XRD), Fourier Transform Infrared spectroscopy(FTIR), transmission electron microscopy(TEM), scanning electron microscopy(SEM), and dynamic light scattering method(DLS)have been used. The results indicate that the ZnO-NAC-Cur NPs exhibit near-spherical morphology and uniform dispersion with an average diameter of ～70 nm. The hemolysis assay shows that ZnO-NAC-Cur NPs has almost no hemolytic activity. In addition, MTT cytotoxicity assessment on B16F10 murine melanoma cells present a drop of IC_(50) values from 17.23 μg·mL~(-1)(free curcumin) to 8.78 μg·mL~(-1)(ZnO-NAC-Cur NPs). This result shows an augmented cancer-inhibitory effect of nanoconjugate complex. In conclusion, the novel ZnO-NAC-Cur NPs could be explored for new therapeutic endeavors.
引文
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[2]Tarhini M,Greige-Gerges H,Elaissari A.Proteinbased nanoparticles:From preparation to encapsulation of active molecules[J].Int J Pharmaceut,2017,522(1-2):172-197.DOI:10.1016/j.ijpharm.2017.01.067.
[3]Zare M,Namratha K,Byrappa K,et al.Surfactant assisted solvothermal synthesis of ZnO nanoparticles and study of their antimicrobial and antioxidant properties[J].J Mater Sci Technol,2018,34(6):1 035-1 043.DOI:10.1016/j.jmst.2017.09.014.
[4]Kr′ol A,Pomastowski P,Rafi′nska K,et al.Zinc oxide nanoparticles:Synthesis,antiseptic activity and toxicity mechanism[J].Adv Colloid Interfac,2017,249:37-52.DOI:10.1016/j.cis.2017.07.033.
[5]Patra S,Verma D,Kole A K,et al.Optical,structural properties and antibacterial activities of uncapped and HMT capped ZnO nanoparticles[J].Materials Today Communications,2017,12:133-145.DOI:10.1016/j.mtcomm.2017.07.003.
[6]Chakraborti S,Mandal A K,Sarwar S,et al.Bactericidal effect of polyethyleneimine capped ZnO nanoparticles on multiple antibiotic resistant bacteria harboring genes of high-pathogenicity island[J].Colloid Surface B,2014,121(9):44-53.
[7]?im?íkováM,Antalík M,KaňuchováM,et al.Anionic11-mercaptoundecanoic acid capped ZnO nanoparticles[J].Appl Surf Sci,2013,282(5):342-347.
[8]刘文虎,袁江北,杨兰,等.姜黄素逆转胃癌细胞赫赛汀耐药机制研究[J].药学学报,2018,53(11):1 817-1 824.Liu W H,Yuan J B,Yang L,et al.Mechanisms of curcumin to reverse herceptin resistance in gastric cancer cells[J].Acta Pharmaceutics Sinica,2018,53(11):1 817-1 824.
[9]陈德,刘意,范凯燕,等.姜黄素微球中药物存在形式与释药行为的关系研究[J].药学学报,2016,51(1):140-146.Chen D,Liu Y,Fan K Y,et al.Relation between drug release and the drug status within curcumin-loaded microsphere[J].Acta Pharmaceutics Sinica,2016,51(1):140-146.
[10]Ibrahim I M,Ali I M,Dheeb B I,et al.Antifungal activity of wide band gap Thioglycolic acid capped ZnS:Mn semiconductor nanoparticles against some pathogenic fungi[J].Mater Sci Eng C-Mater,2017,73:665-669.DOI:10.1016/j.msec.2016.12.121.
[11]Pandimurugan R,Thambidurai S.Novel seaweed capped ZnO nanoparticles for effective dye photodegradation and antibacterial activity[J].Adv Powder Technol,2016,27(4):1 062-1 072.DOI:10.1016/j.apt.2016.03.014.
[12]Khan M F,Ansari A H,Hameedullah M,et al.Sol-gel synthesis of thorn-like ZnO nanoparticles endorsing mechanical stirring effect and their antimicrobial activities:potential role as nano-antibiotics[J].Sci Rep,2016,6:27 689.DOI:10.1038/srep27689.
[13]Rodzinski A,Guduru R,Liang P,et al.Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles[J].Sci Rep,2016,6:20 687.DOI:10.1038/srep20687.
[14]Vijayakumar S,Vaseeharan B.Antibiofilm,anti cancer and ecotoxicity properties of collagen based ZnO nanoparticles[J].Adv Powder Technol,2018,29(10):2 331-2 345.DOI:10.1016/j.apt.2018.06.013.