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TMTP1-Modified, Tumor Microenvironment Responsive Nanoparticles Co-Deliver Cisplatin and Paclitaxel Prodrugs for Effective Cervical Cancer Therapy

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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 [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
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关键词: TME-responsive targeted co-delivery combined chemotherapy cervical cancer

摘要:
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.

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基金编号: 81472444 82002764 81902661

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 2 区 药学 3 区 纳米科技
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 药学 3 区 纳米科技
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出版当年[2019]版:
Q1 PHARMACOLOGY & PHARMACY Q2 NANOSCIENCE & NANOTECHNOLOGY
最新[2023]版:
Q1 NANOSCIENCE & NANOTECHNOLOGY Q1 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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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
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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
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