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.
引用
收藏
页数:13
相关论文
共 73 条
[41]   Raman study of pressure-induced phase transitions in crystals of orthorhombic and monoclinic polymorphs of L-cysteine: dynamics of the side chain [J].
Minkov, Vasily S. ;
Goryainov, Sergei V. ;
Boldyreva, Elena V. ;
Gorbitz, Carl Henrik .
JOURNAL OF RAMAN SPECTROSCOPY, 2010, 41 (12) :1748-1758
[42]   Apoptosis induced by low-dose and low-dose-rate radiation [J].
Mirzaie-Joniani, H ;
Eriksson, D ;
Sheikholvaezin, A ;
Johansson, A ;
Löfroth, PO ;
Johansson, L ;
Stigbrand, T .
CANCER, 2002, 94 (04) :1210-1214
[43]   L-Cysteine conjugated poly L-lactide nanoparticles containing 5-fluorouracil: formulation, characterization, release and uptake by tissues in vivo [J].
Mishra, Brijeshkunvar J. ;
Kaul, Ankur ;
Trivedi, Piyush .
DRUG DELIVERY, 2015, 22 (02) :214-222
[44]  
Munshi A, 2005, METH MOLEC MED, V110, P21
[45]   Radioprotectors in radiotherapy [J].
Nair, CKK ;
Parida, DK ;
Nomura, T .
JOURNAL OF RADIATION RESEARCH, 2001, 42 (01) :21-37
[46]   In vitro and in vivo uptake studies of PAMAM G4.5 dendrimers in breast cancer [J].
Oddone, Natalia ;
Lecot, Nicole ;
Fernandez, Marcelo ;
Rodriguez-Haralambides, Alejandra ;
Cabral, Pablo ;
Cerecetto, Hugo ;
Benech, Juan Claudio .
JOURNAL OF NANOBIOTECHNOLOGY, 2016, 14
[47]   New insights into the structural characteristics of irradiated crotamine [J].
Oliveira, Karina Corleto ;
Spencer, Patrick Jack ;
Ferreira, Rui Seabra, Jr. ;
Nascimento, Nanci .
JOURNAL OF VENOMOUS ANIMALS AND TOXINS INCLUDING TROPICAL DISEASES, 2015, 21
[48]   Half generations magnetic PAMAM dendrimers as an effective system for targeted gemcitabine delivery [J].
Parsian, Maryam ;
Mutlu, Pelin ;
Yalcin, Serap ;
Tezcaner, Aysen ;
Gunduz, Ufuk .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2016, 515 (1-2) :104-113
[49]   CYSTEINE PROTECTION AGAINST X-IRRADIATION [J].
PATT, HM ;
TYREE, EB ;
STRAUBE, RL ;
SMITH, DE .
SCIENCE, 1949, 110 (2852) :213-214
[50]   GAMMA-RADIOLYSIS OF CYSTEINE-CYSTEAMINE DISULFIDE IN AQUEOUS SOLUTION [J].
PURDIE, JW .
CANADIAN JOURNAL OF CHEMISTRY-BACK YEAR, 1971, 49 (05) :725-+