title: In Vitro Evaluation of Doxorubicin Conjugates Based on Sugar Core Nonlinear Polymethacrylates toward Anticancer Drug Delivery.
abstract: V-shaped and star-shaped hydroxylamine-functionalized polymethacrylates designed as nanosized conjugates (<120 nm) with anticancer agent, namely, doxorubicin (DOX), were evaluated in vitro toward their potential usage as drug delivery systems in breast cancer (MCF-7) treatment. Statistical analysis of MTS assay results showed that the 4-arm conjugate (n(DOX) = 16) was the most effective polymeric system against MCF-7/W (wild type) and MCF-7/R (DOX resistant) cell lines. Apoptosis assay analysis showed that MCF-7/R cells cultured with nonlinear copolymers died due to necrosis and late apoptotis, whereas MCF-7/W cells were in early and late apoptosis. Among all tested conjugates, the most promising results with induction of apoptosis without inducing necrosis in both MCF-7 cell lines were obtained for conjugate based on 4-arm stars with low content of DOX. The cell cycle assay revealed that increase of MMA units in 4-arm copolymers induced MCF-7/R cell arrest in the SubG1 phase. In the same cell line, the corresponding conjugates triggered S and G2/M arrest. Gradual internalization of the chosen conjugate by MCF-7/R cells was monitored via fluorescence microscopy showing its main localization in the cytoplasm.
authors.affiliation: Department of Physical Chemistry and Technology of Polymers, Faculty of Chemistry, Silesian University of Technology , M. Strzody 9 Street, 44-100 Gliwice, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Mielańczyk
authors.affiliation: Biosystems Group, Institute of Automatic Control, Silesian University of Technology , Akademicka 16 Street, 44-100 Gliwice, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Skonieczna
authors.affiliation: School of Medicine with the Division of Dentistry in Zabrze, Department of Histology and Embryology, Medical University of Silesia , Jordana 19 Street, 41-808 Zabrze, Poland.
authors.forename: Ł
authors.initials: Ł
authors.lastname: Mielańczyk
authors.affiliation: Department of Physical Chemistry and Technology of Polymers, Faculty of Chemistry, Silesian University of Technology , M. Strzody 9 Street, 44-100 Gliwice, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Neugebauer
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D066298:In Vitro Techniques; D061986:MCF-7 Cells; D011109:Polymethacrylic Acids / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D002241:Carbohydrates; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; D004317:Doxorubicin