Citation: SHAO Shuai, DING Bin-Bin, ZHU Zhong-Li, MA Ping-An, LIN Jun. Preparation of Water-soluble Up-conversion Nano-drug by Host-Guest Chemistry and Its Application in Tumor Diagnosis and Treatment[J]. Chinese Journal of Analytical Chemistry, ;2019, 47(6): 823-831,889. doi: 10.19756/j.issn.0253-3820.191050 shu

Preparation of Water-soluble Up-conversion Nano-drug by Host-Guest Chemistry and Its Application in Tumor Diagnosis and Treatment

SHAO Shuai ^1,2, ,
DING Bin-Bin ² ,
ZHU Zhong-Li ¹ ,
MA Ping-An ² ,
LIN Jun ²

1.
Changchun University of Science and Technology, Changchun 130022, China;
2.
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China

Received Date: 22 January 2019

Fund Project: This work was supported by the National Natural Science Foundation of China (Nos. 51872282, 51672269, 51720105015, 51772124), the Science and Technology Development Planning Project of Jilin Province, China (Nos. 20170204028GX, 20170101188JC, 20180520163JH) and the Youth Innovation Promotion Association of Chinese Academy of Sciences (No.2017273).

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.
- Up-conversion luminescence,
- β-Cyclodextrin,
- Host-guest,
- Photoacoustic imaging,
- Apoptosis
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