title: Gene and doxorubicin co-delivery system for targeting therapy of glioma.
abstract: The combination of gene therapy and chemotherapy is a promising treatment strategy for brain gliomas. In this paper, we designed a co-delivery system (DGDPT/pORF-hTRAIL) loading chemotherapeutic drug doxorubicin and gene agent pORF-hTRAIL, and with functions of pH-trigger and cancer targeting. Peptide HAIYPRH (T7), a transferrin receptor-speciﬁc peptide, was chosen as the ligand to target the co-delivery system to the tumor cells expressing transferrin receptors. T7-modiﬁed co-delivery system showed higher efﬁciency in cellular uptake and gene expression than unmodiﬁed co-delivery system in U87 MG cells, and accumulated in tumor more efﬁciently in vivo. DOX was covalently conjugated to carrier though pH-trigged hydrazone bond. In vitro incubation of the conjugates in buffers led to a fast DOX release at pH 5.0 (intracellular environment) while at pH 7.4 (blood) the conjugates are relatively stable. The combination treatment resulted in a synergistic growth inhibition (combination index, CI < 1) in U87 MG cells. The synergism effect of DGDPT/pORF-hTRAIL was verified in vitro and in vivo. In vivo anti-glioma efﬁcacy study confirmed that DGDPT/pORF-hTRAIL displayed anti-glioma activity but was less toxic.
authors.affiliation: Key Laboratory of Smart Drug Deliver, Ministry of Education and PLA Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Shuhuan
authors.initials: S
authors.lastname: Liu
authors.forename: Yubo
authors.initials: Y
authors.lastname: Guo
authors.forename: Rongqin
authors.initials: R
authors.lastname: Huang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.forename: Shixian
authors.initials: S
authors.lastname: Huang
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Kuang
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry; D015316:Genetic Therapy; D005910:Glioma / Q000188:drug therapy* / Q000628:therapy*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D004317:Doxorubicin