【摘要】 镧系上转换纳米粒子是良好的药物载体和体内成像剂,但表面的疏水性限制了在医学研究中的应用。本研究以具有良好的生物相容性和多功能的主客体性质的β-环糊精（β-CD）为主体,β-2%Er,20%Yb:NaYF₄（β-Er,Yb:NaYF₄）表面的油酸分子为客体,通过主客体作用,采用一步超声法将β-CD修饰到纳米粒子表面,进而将抗肿瘤药物盐酸阿霉素（DOX）通过亲疏水作用负载到油酸分子与β-CD形成的间隙中,获得水溶性的纳米药物载体（β-Er,Yb:NaYF₄@β-CD-DOX）,此药物载体在980 nm近红外光照射下可产生发射波长为540 nm的荧光和光声信号,可实现上转换荧光和光声信号双模式成像。采用X-射线衍射、透射电子显微镜和傅立叶红外光谱分析了β-Er,Yb:NaYF₄@β-CD-DOX纳米药物载体结构,采用紫外-可见分光度法考察药物的载药量和pH敏感性释放,采用细胞内吞实验检测了纳米载体对药物传递和体外成像功能,利用MTT法检测β-Er,Yb:NaYF₄@β-CD-DOX对人源肝癌细胞HepG2增殖的抑制作用,利用光声成像系统和小鼠成像系统检测了药物载体在小鼠肿瘤内的成像效果。结果表明,制备的药物载体β-Er,Yb:NaYF₄@β-CD-DOX具有pH敏感释放效应,显著增强了体外抗肝癌细胞的毒性及诱导肿瘤细胞凋亡,同时具备上转换及光声双模式的体外/体内成像功能。此药物载体有望成为新型药物传递成像载体,用于抗肝癌的治疗研究。更多还原

【Abstract】 Lanthanide up-conversion nanoparticles have attracted considerable interest as potential drug carriers and imaging agents in tumor tissues. However, it has poor water solubility, which limited its applications in medical researches. In this study by taking advantages of good biocompatibility and multifunctional host-guest properties of β-cyclodextrin（β-CD）, the oleic acid ligand on the surface of β-2%Er,20%Yb:NaYF₄（β-Er,Yb:NaYF₄） could be inserted into the hydrophobic cavity of β-CD, improving the water solubility of β-Er,Yb:NaYF₄ by one-step ultrasonic method.Doxorubicin（DOX） was loaded into the gap between oleic acid molecule and β-CD（β-Er,Yb:NaYF₄@β-CD-DOX） by hydrophilic action and it was used in the study of anti-hepatoma in vitro. At 980 nm near-infrared light, 540 nm fluorescence and photoacoustic signals were generated to achieve the purpose of double mode imaging. X ray diffraction（XRD）, transmission electron microscope（TEM） and infrared spectroscopy（IR） were used to analyze the structure of β-Er,Yb:NaYF₄@β-CD of the nano-drug carrier. Endocytosis assay was used to detect the drug delivery and in vitro imaging function. MTT assay was used to detect the inhibitory effect of β-Er,Yb:NaYF₄@β-CD-DOX on the proliferation of HepG2 hepatocytes. The imaging effect of in situ injection of β-Er,Yb:NaYF₄@β-CD-DOX into mouse tumor irradiated with 980 nm near-infrared light. The results showed that the drug carrier of β-Er,Yb:NaYF₄@β-CD was successfully synthesized, as a drug vector with pH-sensitive release effect, which significantly enhanced the toxicity of hepatoma cells and induced apoptosis of tumor cells in vitro. Furthermore, it has excellent up-conversion and photoacoustic imaging function in vivo and in vitro. β-Er,Yb:NaYF₄@β-CD-DOX is expected to be a novel drug transfer imaging carrier and can be used in the treatment of hepatocellular carcinoma.更多还原