title: Co-assembly of doxorubicin and curcumin targeted micelles for synergistic delivery and improving anti-tumor efficacy.
abstract: Chemotherapeutic drugs have a series of limitations in anti-tumor treatment, mainly including multidrug resistance (MDR) and serious adverse reactions. Co-delivery system with two or more synergistic therapeutic drugs is an effective strategy to settle these limitations. In this study, active tumor-targeted co-delivery micelles (DOX+Cur)-PMs, with two synergistic drugs of a therapeutic drug of doxorubicin (DOX) and a chemosensitizer of curcumin (Cur) co-encapsulated into hyaluronic acid-vitamin E succinate (HA-VES) graft copolymer, were prepared and delivered simultaneously into tumor cells for improving therapeutic effects of DOX. (DOX+Cur)-PMs had uniform particle size, high encapsulation efficacy, sustained release profile and good colloidal stability. In vitro cytotoxicity study, (DOX+Cur)-PMs exerted the strongest cytotoxicity and highest cell apoptosis-inducing activities against DOX-resistant MCF-7/Adr cells. Moreover, (DOX+Cur)-PMs more efficiently internalized into cancer cells and enhanced the cellular uptake of DOX via energy-dependent and caveolae-mediated endocytosis, and significantly reversed MDR effects via CD44 targeting delivery and the synergic effect of released Cur. More importantly, in vivo results illustrated that (DOX+Cur)-PMs not only displayed better tumor accumulation and tumor targeting, and more efficiently inhibited the growth of tumor in 4T1 tumor-bearing mice, but also induced significantly less pathological damage to the cardiac tissue in comparison with free DOX, even DOX-PMs and DOX-PMs+Cur. In summary, this targeted combinational micellar delivery system with DOX and Cur could be a promising vehicle in tumor therapy.
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, People's Republic of China.
authors.forename: Wenzhuan
authors.initials: W
authors.lastname: Ma
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China. Electronic address: wangjinling22@163.com.
authors.forename: Jinling
authors.initials: J
authors.lastname: Wang
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China. Electronic address: pengfeitu@163.com.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D003474:Curcumin
keywords: Active targeting; Curcumin; Doxorubicin; Multifunctional micelles; Synergistic anti-tumor