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Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles

文献类型： 外文期刊

作者： Wang, Yichao 1 ; Li, Puwang 1 ; Chen, Lijue 1 ; Gao, Weimin 1 ; Zeng, Fanbo 3 ; Kong, Ling Xue 1 ;

作者机构： 1.Deakin Univ, Inst Frontier Mat, Waurn Ponds, Vic 3216, Australia

2.Chinese Acad Trop Agr Sci, Agr Prod Proc Res Inst, Zhanjiang, Peoples R China

3.Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan 430074, Peoples R China

关键词： HT-29;nanoparticles;PLGA-1;3-diaminopropane-folic acid;targeting

期刊名称：DRUG DELIVERY （ 影响因子：6.419； 五年影响因子：6.169 ）

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收录情况： SCI

摘要： The incorporation of a high percentage of targeting molecules into drug delivery system is one of the important methods for improving efficacy of targeting therapeutic drugs to cancer cells. PLGA-based drug delivery carriers with folic acid (FA) as targeting molecule have a low targeting efficiency due to a low FA conjugation ratio. In this work, we fabricated a FA-conjugated PLGA system using a crosslinker 1, 3-diaminopropane and have achieved a high conjugation ratio of 46.7% (mol/mol). The as-prepared PLGA-based biomaterial was used to encapsulate therapeutic drug 5-fluorouracil (5-FU) into nanoparticles. In the in vitro experiments, an IC50 of 5.69 mg/mL has been achieved for 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles on HT-29 cancer cells and is significantly lower than that of 5-FU and 5-FU loaded PLGA nanoparticles which only have an IC50 of 22.9 and 14.17 mg/mL, respectively. The fluorescent microscopy images showed that nanoparticles with FA are largely taken up by HT-29 cancer cells and the targeting nanoparticles have more affinity to cancer cells than the pure drugs and untreated nanoparticles. Therefore, the 1, 3-diaminopropane can facilitate the conjugation of FA to PLGA to form a novel polymer and 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles can be a highly efficient system for specific delivery of drugs to cancer cells.

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[1]Development of Ligand Incorporated Chitosan Nanoparticles for the Selective Delivery of 5-Fluorouracil to Colon. Li, Puwang,She, F. H.,Kong, L. X.,Li, Puwang,Li, Puwang,Peng, Zheng. 2011

[2]Chitosan-Modified PLGA Nanoparticles with Versatile Surface for Improved Drug Delivery. Wang, Yichao,Li, Puwang,Kong, Lingxue,Li, Puwang. 2013

[3]Formulation Optimization For High Drug Loading Colonic Drug Delivery Carrier. Wang, Yichao,Li, Puwang,Kong, Lingxue,Peng, Zheng,Luo, Yongyue. 2010

[4]Formulation of vanillin cross-linked chitosan nanoparticles and its characterization. Wang, Guang,Li, Puwang,Peng, Zheng,Huang, Maofang,Kong, Lingxue. 2011

[5]Manufacturing Techniques and Surface Engineering of Polymer Based Nanoparticles for Targeted Drug Delivery to Cancer. Wang, Yichao,Wang, Yichao,Li, Puwang,Thao Truong-Dinh Tran,Zhang, Juan,Kong, Lingxue,Li, Puwang,Thao Truong-Dinh Tran. 2016

[6]Development of drug-loaded chitosan-vanillin nanoparticles and its cytotoxicity against HT-29 cells. Li, Pu-Wang,Wang, Guang,Yang, Zi-Ming,Peng, Zheng,Wang, Qing-Huang,Duan, Wei,Kong, Ling-Xue,Wang, Qing-Huang.

[7]Synthesis and characterization of chitosan quaternary ammonium salt and its application as drug carrier for ribavirin. Li, Si-Dong,Quan, Wei-Yan,Yang, Lei,Dong, Jing-Jing,Li, Pu-Wang,Yang, Zi-Ming,Peng, Zheng,Yang, Xi-Hong.

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