Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles
| Autor: | Shuai Shi, Jinyi Lang, Chuntang Sun, Le Zhou, Maling Gou, Tao Li |
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| Rok vydání: | 2016 |
| Předmět: |
Cancer Research
Cell Survival Polyesters macromolecular substances 02 engineering and technology Biology Polyethylene Glycols Mice 03 medical and health sciences 0302 clinical medicine Therapeutic index Cell Line Tumor Neoplasms polycyclic compounds medicine Animals Humans Doxorubicin Micelles Zebrafish Cell Proliferation A549 cell Drug Carriers Antibiotics Antineoplastic Cell growth Myocardium organic chemicals technology industry and agriculture Biological Transport Heart General Medicine 021001 nanoscience & nanotechnology Molecular medicine Mice Inbred C57BL carbohydrates (lipids) Oncology A549 Cells Apoptosis 030220 oncology & carcinogenesis Toxicity Cancer research Nanoparticles Female 0210 nano-technology Drug carrier medicine.drug |
| Zdroj: | Oncology Reports. 35:3600-3606 |
| ISSN: | 1791-2431 1021-335X |
| Popis: | Doxorubicin (Dox) is a broad-spectrum antitumor drug used for the treatment of many types of malignant tumors. Although it possesses powerful antitumor activity, its clinical application is seriously encumbered by its unselective distribution and systemic toxicities, particularly myocardial toxicity. Thus, it is imperative to modify Dox to decrease its systemic toxicities and improve its therapeutic index. In the present study, we adopted a novel type of monomethoxy poly(ethylene glycol)-poly(e-caprolactone) (MPEG-PCL) micelles to encapsulate Dox to prepare Dox-loaded MPEG-PCL (Dox/MPEG-PCL) nanoparticles by a controllable self-assembly process. The cellular uptake efficiency and cell proliferation inhibition of the Dox/MPEG-PCL nanoparticles were examined. The antitumor activity of the Dox/MPEG-PCL nanoparticles was tested on a multiple pulmonary metastasis model of melanoma on C57BL/6 mice. Systemic toxicities and survival time were compared between the mice treated with the Dox/MPEG-PCL nanoparticles and free Dox. The potential myocardial toxicity of the Dox/MPEG-PCL nanoparticles was investigated using a prolonged observation period. Encapsulation of Dox in MPEG-PCL nanoparticles significantly improved the cellular uptake and cell proliferation inhibition of Dox in vivo. Intravenous injection of Dox/MPEG-PCL nanoparticles obtained significant inhibition of the growth and metastasis of melanoma in the lung and prolonged survival time compared with free Dox (P |
| Databáze: | OpenAIRE |
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