Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model.

Autor: Peng ZH; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 69198, USA.; Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA., Jogdeo CM; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 69198, USA., Li J; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 69198, USA., Xie Y; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 69198, USA., Wang Y; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 69198, USA., Sheinin YM; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 69198, USA.; Department of Pathology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI 53226, USA., Kopeček J; Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA., Oupický D; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 69198, USA.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2022 Aug 18; Vol. 14 (8). Date of Electronic Publication: 2022 Aug 18.
DOI: 10.3390/pharmaceutics14081725
Abstrakt: Tremendous progress has been made in the field of nanomedicine for cancer treatment. However, most of the research to date has been focused on inhibiting primary tumor growth with comparatively less efforts directed towards managing tumor metastasis. Here, we introduce a polymeric conjugate P-DOX-iRGD that not only significantly suppressed primary tumor growth but also substantially inhibited pulmonary metastasis in an orthotopic mouse model of breast cancer. In addition, treatment with P-DOX-iRGD markedly reduced breast cancer-induced splenomegaly and liver hematopoiesis. Interestingly, contrasting results were seen for the free form and polymeric form of DOX in vitro and in vivo, which may be attributed to the enhanced permeability and retention (EPR) effect.
Databáze: MEDLINE
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