单位:[1]Department of Obstetrics & Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science &Technology,Wuhan,Hubei Province,People’s Republic of China华中科技大学同济医学院附属同济医院妇产科学系围产医学科[2]Tongji School ofPharmacy, Tongji Medical College, HuazhongUniversity of Science & Technology, Wuhan,Hubei Province, People’s Republic of China[3]School of Pharmacy, Shanghai Jiao TongUniversity, Shanghai, People’s Republic of China
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.
基金:
National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472444, 82002764, 81902661]
第一作者单位:[1]Department of Obstetrics & Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science &Technology,Wuhan,Hubei Province,People’s Republic of China
共同第一作者:
通讯作者:
通讯机构:[1]Department of Obstetrics & Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science &Technology,Wuhan,Hubei Province,People’s Republic of China[*1]Department of Obstetrics & Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science & Technology,Wuhan,Hubei,People’s Republic of China
推荐引用方式(GB/T 7714):
Jiang Guiying,Wang Xueqian,Zhou Ying,et al.TMTP1-Modified, Tumor Microenvironment Responsive Nanoparticles Co-Deliver Cisplatin and Paclitaxel Prodrugs for Effective Cervical Cancer Therapy[J].INTERNATIONAL JOURNAL OF NANOMEDICINE.2021,16:4087-4104.doi:10.2147/IJN.S298252.
APA:
Jiang, Guiying,Wang, Xueqian,Zhou, Ying,Zou, Chenming,Wang,Ling...&Xi, Ling.(2021).TMTP1-Modified, Tumor Microenvironment Responsive Nanoparticles Co-Deliver Cisplatin and Paclitaxel Prodrugs for Effective Cervical Cancer Therapy.INTERNATIONAL JOURNAL OF NANOMEDICINE,16,
MLA:
Jiang, Guiying,et al."TMTP1-Modified, Tumor Microenvironment Responsive Nanoparticles Co-Deliver Cisplatin and Paclitaxel Prodrugs for Effective Cervical Cancer Therapy".INTERNATIONAL JOURNAL OF NANOMEDICINE 16.(2021):4087-4104