Guiying Jiang1, Xueqian Wang1, Ying Zhou1, Chenming Zou2,3, Ling Wang1, Wei Wang1, Danya Zhang1, Hanjie Xu1, Jie Li1, Fei Li1, Danfeng Luo1, Xiangyi Ma1, Ding Ma1, Songwei Tan2, Rui Wei1, Ling Xi1. 1. Department of Obstetrics & Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, People's Republic of China. 2. Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, People's Republic of China. 3. School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Abstract
BACKGROUND AND PURPOSE: Cisplatin-paclitaxel (TP) combination chemotherapy as the first-line therapy for numerous cancers is hindered by its inadequate accumulation in tumors and severe side effects resulting from non-specific distribution. The aim of this study is to explore whether TMTP1-modified, cisplatin and paclitaxel prodrugs co-loaded nanodrug could improve cervical cancer chemotherapy and relieve its side effects through active and passive tumor targeting accumulation and controlled drug release. METHODS: TDNP, with capacities of active targeting for tumors and controlled drug release, was prepared to co-deliver cisplatin and paclitaxel prodrugs. The characteristics were investigated, including the diameter, surface zeta potential, stability and tumor microenvironment (TME) dependent drug release profiles. Cellular uptake, cytotoxicity, drug accumulation in tumors, antitumor effects and safety analysis were evaluated in vitro and in vivo. RESULTS: The oxidized cisplatin and the paclitaxel linked to the polymer achieved a high loading effciency of over 80% and TME-dependent sustained drug release. Moreover, TMTP1 modification enhanced cellular uptake of TDNP and further improved the cytotoxicity of TDNP in vitro. In vivo, TDNP showed an extended blood circulation and increased accumulation in SiHa xenograft models with the aid of TMTP1. More importantly, TDNP controlled tumor growth without life-threatening side effects. CONCLUSION: Our study provided a novel TP co-delivery platform for targeted chemotherapy of cervical cancer, which was promising to improve the therapeutic effcacy of TP and may also have application in other tumors.
BACKGROUND AND PURPOSE: Cisplatin-paclitaxel (TP) combination chemotherapy as the first-line therapy for numerous cancers is hindered by its inadequate accumulation in tumors and severe side effects resulting from non-specific distribution. The aim of this study is to explore whether TMTP1-modified, cisplatin and paclitaxel prodrugs co-loaded nanodrug could improve cervical cancer chemotherapy and relieve its side effects through active and passive tumor targeting accumulation and controlled drug release. METHODS: TDNP, with capacities of active targeting for tumors and controlled drug release, was prepared to co-deliver cisplatin and paclitaxel prodrugs. The characteristics were investigated, including the diameter, surface zeta potential, stability and tumor microenvironment (TME) dependent drug release profiles. Cellular uptake, cytotoxicity, drug accumulation in tumors, antitumor effects and safety analysis were evaluated in vitro and in vivo. RESULTS: The oxidized cisplatin and the paclitaxel linked to the polymer achieved a high loading effciency of over 80% and TME-dependent sustained drug release. Moreover, TMTP1 modification enhanced cellular uptake of TDNP and further improved the cytotoxicity of TDNP in vitro. In vivo, TDNP showed an extended blood circulation and increased accumulation in SiHa xenograft models with the aid of TMTP1. More importantly, TDNP controlled tumor growth without life-threatening side effects. CONCLUSION: Our study provided a novel TP co-delivery platform for targeted chemotherapy of cervical cancer, which was promising to improve the therapeutic effcacy of TP and may also have application in other tumors.
Authors: Goran N Kaludjerović; Djordje Miljković; Miljana Momcilović; Vesna M Djinović; Marija Mostarica Stojković; Tibor J Sabo; Vladimir Trajković Journal: Int J Cancer Date: 2005-09-01 Impact factor: 7.396
Authors: Jing Tian; Yuanzeng Min; Zachary Rodgers; Kin Man Au; C Tilden Hagan; Maofan Zhang; Kyle Roche; Feifei Yang; Kyle Wagner; Andrew Z Wang Journal: J Mater Chem B Date: 2017-07-05 Impact factor: 6.331