title: Synergistic inhibition of breast cancer by co-delivery of VEGF siRNA and paclitaxel via vapreotide-modified core-shell nanoparticles.
abstract: A somatostatin analog, vapreotide (VAP), can be used as a ligand for targeting drug delivery based on its high affinity to somatostatin receptors (SSTRs), which is overexpressed in many tumor cells. RNA interference plays an important role on downregulation of vascular endothelial growth factor (VEGF), which is important for tumor growth, progression and metastasis. To improve tumor therapy efficacy, the vapreotide-modified core-shell type nanoparticles co-encapsulating VEGF targeted siRNA (siVEGF) and paclitaxel (PTX), termed as VAP-PLPC/siRNA NPs, were developed in this study. When targeted via somatostatin receptors to tumor cells, the VAP-PLPC/siRNA NPs could simultaneously delivery siVEGF and PTX into cells and achieve a synergistic inhibition of tumor growth. Interestingly, in vitro cell uptake and gene silencing experiments demonstrated that the targeted VAP-PLPC/siRNA NPs exhibited significant higher intracellular siRNA accumulation and VEGF downregulation in human breast cancer MCF-7 cells, compared to those of the non-targeted PEG-PLPC/siRNA NPs. More importantly, in vivo results further demonstrated that the targeted VAP-PLPC/siRNA NPs had significant stronger drug distribution in tumor tissues and tumor growth inhibition efficacy via receptor-mediated targeting delivery, accompany with an obvious inhibition of neovascularization induced by siVEGF silencing. These results suggested that the co-delivery of siRNA and paclitaxel via vapreotide-modified core-shell nanoparticles would be a promising approach for tumor targeted therapy.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Min-Zhi
authors.initials: MZ
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China. Electronic address: wang-jc@bjmu.edu.cn.
authors.forename: Jian-Cheng
authors.initials: JC
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Ling-Yan
authors.initials: LY
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Xi-Wei
authors.initials: XW
authors.lastname: Pei
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Chong
authors.initials: C
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Pang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Du
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of pharmaceutical sciences, Peking University, Beijing 100191, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000628:therapy; D002453:Cell Cycle / Q000187:drug effects; D015536:Down-Regulation; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D017481:Receptors, Somatostatin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C051458:vapreotide; D013004:Somatostatin; D017239:Paclitaxel
keywords: Co-delivery; Core-shell nanoparticle; Paclitaxel; Tumor targeting therapy; VEGF targeted siRNA; Vapreotide