Citation: Fan-Fan Fu, Ben-Qing Zhou, Zhi-Jun Ouyang, Yi-Lun Wu, Jing-Yi Zhu, Ming-Wu Shen, Jin-Dong Xia, Xiang-Yang Shi. Multifunctional Cholesterol-modified Dendrimers for Targeted Drug Delivery to Cancer Cells Expressing Folate Receptors[J]. Chinese Journal of Polymer Science, ;2019, 37(2): 129-135. doi: 10.1007/s10118-019-2172-9 shu

Multifunctional Cholesterol-modified Dendrimers for Targeted Drug Delivery to Cancer Cells Expressing Folate Receptors

Fan-Fan Fu ^1,† ,
Ben-Qing Zhou ^1,† ,
Zhi-Jun Ouyang ¹ ,
Yi-Lun Wu ¹ ,
Jing-Yi Zhu ¹ ,
Ming-Wu Shen ^1,, ,
Jin-Dong Xia ^2,, ,
Xiang-Yang Shi ^1,2,,

a.
Key Laboratory of Science & Technology of Eco-Textile, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
b.
Department of Radiology, Shanghai Songjiang District Central Hospital, Shanghai 201600, China

Corresponding author: Ming-Wu Shen, mwshen@dhu.edu.cn Jin-Dong Xia, xiajd_21@163.com Xiang-Yang Shi, xshi@dhu.edu.cn
Received Date: 29 July 2018
Revised Date: 14 September 2018
Accepted Date: 18 September 2018
Available Online: 22 October 2018

We present here the development of cholesterol (Chol)-modified dendrimer system for targeted chemotherapy of folate (FA) receptor-expressing cancer cells. In our study, poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5) were functionalized step-by-step with Chol, fluorescein isothiocyanate (FI), and FA via a poly(ethylene glycol) (PEG) spacer (PEG-FA), and then acetamide to shield their remaining surface amines. The synthesized G5.NHAc-Chol-FI-PEG-FA (for short, G5-CFPF) dendrimers were utilized to encapsulate 10-hydroxycamptothecin (HCP), a hydrophobic anticancer drug. We find that each G5-CFPF dendrimer can encapsulate 13.8 HCP molecules. The complexes show a slower release profiles of HCP in a pH-dependent manner than the control complexes formed using the same dendrimers without Chol under the same conditions. Thanks to the targeting role played by FA, the complexes display a specific inhibition efficacy to FA receptor-expressing cervical cancer cells. The designed Chol-modified dendrimers may be adopted as a promising carrier for application in targeted cancer therapy.
- PAMAM dendrimers,
- Folate,
- Cholesterol,
- 10-Hydroxycamptothecin,
- Targeted cancer therapy
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