title: Lipid nanoparticle-based co-delivery of epirubicin and BCL-2 siRNA for enhanced intracellular drug release and reversing multidrug resistance.
abstract: At present, combined therapy has become an effective strategy for the treatment of cancer. Co-delivery of the chemotherapeutic drugs and siRNA can more effectively inhibit tumor growth by nano drug delivery systems (NDDSs). Here, we prepared and evaluated a multifunctional envelope-type nano device (MEND). This MEND was a kind of composite lipid-nanoparticles possessing both the properties of liposomes and nanoparticles. In this study, an acid-cleavable ketal containing poly (β-amino ester) (KPAE) was used to bind siBCL-2 and the KPAE/siBCL-2 complexes were further coated by epirubicin (EPI) containing lipid to form EPI/siBCL-2 dual loaded lipid-nanoparticles. The results showed that the average size of EPI/siBCL-2-MEND was about 120 nm, and the average zeta potential was about 41 mV. The encapsulation efficiency (EE) of EPI and siBCL-2 was 86.13% and 97.07%, respectively. EPI/siBCL-2 dual loaded lipid-nanoparticles showed enhanced inhibition efficiency than individual EPI-loaded liposomes on HepG2cells by MTT assay. Moreover, western blot experiment indicated co-delivery of EPI/siBCL-2 can significantly down-regulate the expression of P-glycoprotein (P-gp), while free EPI and EPI-loaded liposomes up-regulated it. Therefore, the strategy of co-delivering EPI and siBCL-2 simultaneously by lipid-nanoparticles showed promising potential in reversing multidrug resistance of tumor cells.
authors.affiliation: a School of Pharmacy, Qingdao University , Qingdao , China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: a School of Pharmacy, Qingdao University , Qingdao , China.
authors.forename: Shangcong
authors.initials: S
authors.lastname: Han
authors.affiliation: b Department of Neurology , Shengli Hospital , Dongying , China.
authors.forename: Zhongai
authors.initials: Z
authors.lastname: Kou
authors.affiliation: a School of Pharmacy, Qingdao University , Qingdao , China.
authors.forename: Jialing
authors.initials: J
authors.lastname: Dai
authors.affiliation: a School of Pharmacy, Qingdao University , Qingdao , China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Liu
authors.affiliation: a School of Pharmacy, Qingdao University , Qingdao , China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wei
authors.affiliation: a School of Pharmacy, Qingdao University , Qingdao , China.
authors.forename: Yitong
authors.initials: Y
authors.lastname: Li
authors.affiliation: a School of Pharmacy, Qingdao University , Qingdao , China.
authors.forename: Lutao
authors.initials: L
authors.lastname: Jiang
authors.affiliation: a School of Pharmacy, Qingdao University , Qingdao , China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D065546:Drug Liberation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004705:Endocytosis; D015251:Epirubicin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000235:genetics*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D008055:Lipids; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D015251:Epirubicin
keywords: Multifuctional envelope-type nano device; epirubicin; multidrug resistance; siRNA