Citation: Hua Guo, Cheng-ling Yang, Wei Wang, Yu-kun Wu, Quan-yong Lai, Zhi Yuan. Studies on Antineoplastic Effect by Adjusting Ratios of Targeted-ligand and Antitumor Drug[J]. Chinese Journal of Polymer Science, ;2014, 32(5): 540-550. doi: 10.1007/s10118-014-1432-y shu

Studies on Antineoplastic Effect by Adjusting Ratios of Targeted-ligand and Antitumor Drug

Hua Guo ¹ ,
Cheng-ling Yang ¹ ,
Wei Wang ¹ ,
Yu-kun Wu ¹ ,
Quan-yong Lai ¹ ,
Zhi Yuan ^1,,

1.
Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Nankai University and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China

Corresponding author: Zhi Yuan,
Received Date: 27 December 2013
Revised Date: 17 February 2014

Fund Project: This work was financially supported by the National Natural Science Foundation of China (Nos. 51073080 and 51273095), Natural Science Foundation of Tianjin (No. 13JCYBJC25100) and PCSIRT (No. IRT1257).

A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid (GA) and doxorubicin (DOX) conjugates at different ratios. GA (a liver-targeting ligand) and DOX (an antitumor drug) were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate (ALG-mOEG) for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. In addition, nanoparticles with a 1:1 (W:W) ratio of GA-ALG-mOEG and DOX-ALG-mOEG (NPs-3) showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 g/g 3 h after injection, and AUC0- and t1/2 of DOX in liver reached 4744.9 gh/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth (88.37% reduction in tumor weight) 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.
- Sodium alginate derivative,
- Drug delivery,
- Targeted-ligand,
- Antitumor drug,
- Antineoplastic effect
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