Overcoming tumor resistance to cisplatin through micelle-mediated combination chemotherapy
| Autor: | Yanxin Qi, Yuwei Cong, Xuesi Chen, Hejian Xiong, Dongfang Zhou, Shasha He, Yanjuan Wu, Xiabin Jing, Zhigang Xie, Yubin Huang |
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| Rok vydání: | 2015 |
| Předmět: |
DNA Repair
Organoplatinum Compounds Cell Survival DNA repair medicine.medical_treatment Biomedical Engineering Drug resistance Pharmacology Piperazines Bridged Bicyclo Compounds In vivo Cell Line Tumor medicine Humans Prodrugs General Materials Science Protein Phosphatase 2 Micelles Cisplatin Chemotherapy Chemistry Combination chemotherapy Prodrug Endocytosis Drug Resistance Neoplasm Cancer cell Drug Therapy Combination medicine.drug |
| Zdroj: | Biomaterials Science. 3:182-191 |
| ISSN: | 2047-4849 2047-4830 |
| Popis: | The main obstacles to cancer therapy are the inability to target cancer cells and the acquired drug resistance after a period of chemotherapy. Reduced drug uptake and DNA repair are the two main mechanisms involved in cisplatin resistance. In the present investigation, canthaplatin, a Pt(iv) pro-drug of cisplatin and a protein phosphatase 2A (PP2A) inhibitor (4-(3-carboxy-7-oxa-bicyclo[2.2.1]heptane-2-carbonyl)piperazine-1-carboxylic acid tert-butyl ester), was designed and delivered using PEG-b-PLGA micelles for combination chemotherapy. Polymer/canthaplatin micelles facilitated the delivery of the drug into cancer cells through endocytosis and diminished DNA repair by PP2A inhibition, resulting in enhanced anti-tumor efficiency and excellent reversal ability of tumor resistance to cisplatin both in vitro and in vivo. Additionally, the polymer/canthaplatin micelles could prolong drug residence in the blood and decrease the side effects when compared to cisplatin. |
| Databáze: | OpenAIRE |
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