Radiation-Sensitive Dendrimer-Based Drug Delivery System

被引:54
作者
Wu, Szu-Yuan [1 ,2 ]
Chou, Hsiao-Ying [3 ]
Yuh, Chiou-Hwa [4 ,5 ,6 ]
Mekuria, Shewaye Lakew [3 ]
Kao, Yu-Chih [3 ]
Tsai, Hsieh-Chih [3 ]
机构
[1] Taipei Med Univ, Wan Fang Hosp, Dept Radiat Oncol, Taipei 116, Taiwan
[2] Taipei Med Univ, Coll Med, Sch Med, Dept Internal Med, Taipei 110, Taiwan
[3] Natl Taiwan Univ Sci & Technol, Grad Inst Appl Sci & Technol, Taipei 106, Taiwan
[4] Natl Hlth Res Inst, Inst Mol & Genom Med, Miaoli 350, Taiwan
[5] Natl Tsing Hua Univ, Inst Bioinformat & Struct Biol, Hsinchu 300, Taiwan
[6] Natl Chiao Tung Univ, Dept Biol Sci & Technol, Hsinchu 300, Taiwan
关键词
combination therapies; dendrimers; doxorubicin; HeLa cells; zebrafish; IN-VITRO; IONIZING-RADIATION; CELL-SURVIVAL; NANOPARTICLES; DOXORUBICIN; RADIOTHERAPY; DISULFIDE; RELEASE; VIVO; RADIOPROTECTORS;
D O I
10.1002/advs.201700339
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Combination of chemotherapy and radiotherapy is used to enhance local drug delivery while reducing off-target tissue effects. Anticancer drug doxorubicin (DOX) is loaded into L-cysteine modified G4.5 dendrimer (GC/DOX) and released at different pH values in the presence and absence of gamma-radiation. Presence of gamma-radiation significantly improves DOX release from the GC/DOX under acidic pH conditions, suggesting that GC dendrimer is a radiation-sensitive drug delivery system. GC/DOX is further evaluated by determining cytotoxicity in uterine cervical carcinoma HeLa cells. GC/DOX shows high affinity for cancer cells and effective drug release following an external stimulus (radiation exposure), whereas an in vivo zebrafish study confirms that l-cysteine acts as a radiosensitizer. GC/DOX treatment combined with radiotherapy synergistically and successfully inhibits cancer cell growth.
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页数:13
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