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Evaluation of linear versus star-like polymer anti-cancer nanomedicines in mouse models
L. Kostka, L. Kotrchová, E. Randárová, CA. Ferreira, I. Malátová, HJ. Lee, AP. Olson, JW. Engle, M. Kovář, W. Cai, M. Šírová, T. Etrych
Language English Country Netherlands
Document type Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural
Grant support
P30 CA014520
NCI NIH HHS - United States
- MeSH
- Doxorubicin pharmacokinetics MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Nanomedicine MeSH
- Drug Carriers * chemistry MeSH
- Polymers * chemistry MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Nanomedicines are considered next generation therapeutics with advanced therapeutic properties and reduced side effects. Herein, we introduce tailored linear and star-like water-soluble nanosystems as stimuli-sensitive nanomedicines for the treatment of solid tumors or hematological malignancies. The polymer carrier and drug pharmacokinetics were independently evaluated to elucidate the relationship between the nanosystem structure and its distribution in the body. Positron emission tomography and optical imaging demonstrated enhanced tumor accumulation of the polymer carriers in 4T1-bearing mice with increased tumor-to-blood and tumor-to-muscle ratios. Additionally, there was a significant accumulation of doxorubicin bound to various polymer carriers in EL4 tumors, as well as excellent in vivo therapeutic activity in EL4 lymphoma and moderate efficacy in 4T1 breast carcinoma. The linear nanomedicine showed at least comparable pharmacologic properties to the star-like nanomedicines regarding doxorubicin transport. Therefore, if multiple parameters are considered such as its optimized structure and simple and reproducible synthesis, this polymer carrier system is the most promising for further preclinical and clinical investigations.
Department of Biomedical Engineering University of Wisconsin Madison Madison WI United States
Department of Pharmaceutical Sciences University of Wisconsin Madison Madison WI United States
References provided by Crossref.org
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