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

Department of Pharmaceutical Sciences University of Wisconsin Madison Madison WI United States; Departments of Radiology and Medical Physics University of Wisconsin Madison Madison WI United States

Departments of Radiology and Medical Physics University of Wisconsin Madison Madison WI United States

Institute of Macromolecular Chemistry CAS Department of Biomedical Polymers Heyrovského nám 2 Prague 6 16206 Czech Republic

Institute of Microbiology CAS Laboratory of Tumor Immunology Vídeňská 1083 Prague 4 14220 Czech Republic

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