title: Phenylboronic acid-functionalized polyamidoamine-mediated Bcl-2 siRNA delivery for inhibiting the cell proliferation.
abstract: In this study, the conjugation of phenylboronic acid (PBA) to amine-terminated polyamidoamine (PAMAM) was successfully conducted to prepare a tumor-targeted gene carrier PBA-functionalized PAMAM (PPP) for Bcl-2 siRNA delivery, using a heterobifunctional crosslinker NHS-PEG5k-Mal. The carrier possessed favorable capacity for siRNA condensation and could protect siRNA from the degradation against RNase and serum. The introduction of PBA could facilitate the cellular uptake and further transfection of Bcl-2 siRNA demonstrated by confocal laser scanning microscopy and flow cytometry. Meanwhile, PPP-mediated transfection of Bcl-2 siRNA could significantly inhibit the expression of Bcl-2 gene at both mRNA and protein levels. Furthermore, owing to the knock-down of Bcl-2, PPP/siRNA could significantly inhibit the cell proliferation by inducing the cell apoptosis, and also enhance the antitumor efficiency of doxorubicin by suppressing the resistance of tumor cells to chemotherapeutics. In conclusion, the PPP-mediated Bcl-2 siRNA delivery could potentially be an effective platform for solving the drug resistance and further achieving the combined chemotherapy and gene therapy in tumor treatment.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Jiebing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xing
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Haobo
authors.initials: H
authors.lastname: Han
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China. Electronic address: yyan@jlu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China. Electronic address: quanshun@jlu.edu.cn.
authors.forename: Quanshun
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D001897:Boronic Acids / Q000737:chemistry*; D019556:COS Cells; D049109:Cell Proliferation / Q000187:drug effects*; D002522:Chlorocebus aethiops; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*
chemical_list: D001672:Biocompatible Materials; D001897:Boronic Acids; D050091:Dendrimers; C104700:PAMAM Starburst; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C010686:benzeneboronic acid
keywords: Bcl-2; Cell proliferation; Multidrug resistance; Phenylboronic acid; Polyamidoamine; siRNA delivery