title: Synergistic Cisplatin/Doxorubicin Combination Chemotherapy for Multidrug-Resistant Cancer via Polymeric Nanogels Targeting Delivery.
abstract: Combination chemotherapy has been proposed to achieve synergistic effect and minimize drug dose for cancer treatment in clinic application. In this article, the stimuli-responsive polymeric nanogels (<100 nm in size) based on poly(acrylic acid) were designed as codelivery system for doxorubicin and cisplatin to overcome drug resistance. By chelation, electrostatic interaction, and π-π stacking interactions, the nanogels could encapsulate doxorubicin and cisplatin with designed ratio and high capacity. Compared with free drugs, the nanogels could deliver more drugs into MCF-7/ADR cells. Significant accumulation in tumor tissues was observed in the biodistribution experiments. The in vitro antitumor studies demonstrated the superior cell-killing activity of the nanogel drug delivery system with a combination index of 0.84, which indicated the great synergistic effect. All the antitumor experimental data revealed that the combination therapy was effective for the multidrug-resistant MCF-7/ADR tumor with reduced side effects.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, and Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University , Shanghai 200433, China.
authors.forename: Haiqiu
authors.initials: H
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200030, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200030, China.
authors.forename: Cun
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, and Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University , Shanghai 200433, China.
authors.forename: Zihao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200030, China.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Ruan
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, and Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University , Shanghai 200433, China.
authors.forename: Luyan
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200030, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, and Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University , Shanghai 200433, China.
authors.forename: Yongjing
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200030, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, and Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University , Shanghai 200433, China.
authors.forename: Changchun
authors.identifier: http://orcid.org/0000-0003-3183-2160
authors.initials: C
authors.lastname: Wang
mesh_terms: D002945:Cisplatin; D004317:Doxorubicin; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles
chemical_list: D004317:Doxorubicin; D002945:Cisplatin
keywords: CDDP; combination chemotherapy; doxorubicin; multidrug-resistant; nanogel; stimuli-responsive