Cationic lipid–DNA complexes—lipoplexes—for gene transfer and therapy

Жданов, Р. И.; Podobed, O. V.; Vlassov, V. V.

doi:10.1016/s1567-5394(02)00132-9

Cited by 161 publications

(106 citation statements)

References 83 publications

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“…These experimental results indicate the ability of divalent cations to compact DNA into structures similar to those observed for DNA+lipid+cationic surfactant aggregates Radler et al, 1997). The ability of these aggregates to serve as vehicles for gene delivery was demonstrated in (Kovalenko et al, 1996;Sato et al, 2005;Zhdanov et al, 1997). However, the structure of the aggregates is of interest also as a model for contact sites between DNA and biomembranes (Kuvichkin, 1990).…”

Section: Introductionmentioning

confidence: 76%

The structural diversity of DNA–neutral phospholipids–divalent metal cations aggregates: a small-angle synchrotron X-ray diffraction study

Uhrı́ková

Lengyel

Hanulová³

et al. 2006

Eur Biophys J

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Section: Introductionmentioning

confidence: 76%

The structural diversity of DNA–neutral phospholipids–divalent metal cations aggregates: a small-angle synchrotron X-ray diffraction study

Uhrı́ková

Lengyel

Hanulová³

et al. 2006

Eur Biophys J

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“…3,4) Unlike viruses, they have no restrictions on the size of DNA to be delivered; CL can deliver nucleic acids of essentially unlimited size ranging up to large mammalian artificial chromosomes. CL can also be covalently grafted to receptor-specific ligands for targeted gene delivery.…”

mentioning

confidence: 99%

Complex Formation with Plasmid DNA Increases the Cytotoxicity of Cationic Liposomes

Nguyen

Atobe

Barichello

et al. 2007

Biological & Pharmaceutical Bulletin

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Cationic liposomes (CL) are one of the most widely studied non-viral vectors for gene delivery. It is wellknown that CL induces cytotoxicity following lipofection. However, little is known regarding the mechanism involved in the cytotoxicity. In this study, the in vitro cytotoxicity of CL and its complex with pDNA (lipoplex) was investigated, and a part of the mechanism of induction as well. While free pDNA did not show any cytotoxicity, pDNA increased the cytotoxicity of CL via the formation of lipoplex. In addition, the lipoplex-induced cytotoxicity increased in a lipoplex dose-dependent manner, irrespective of the type of pDNA, cell line and the absence or presence of serum. An assay showed that apoptosis was largely induced by treatment with the lipoplex (lipofection), but not with CL alone, in the tested range of concentration of CL and pDNA. Furthermore, following treatment with lipoplexes, the cells exhibited the morphological features of apoptosis and DNA fragmentation. A cDNA microarray study showed that the lipofection up-regulated 45 genes related to apoptosis, transcription regulation and immune response. These results clearly indicate that pDNA in the lipoplex increases the cytotoxicity of CL as a result of inducing apoptosis. The fundamental principle for gene therapy is to deliver gene-based therapeutics to target cells for specific gene targeting with minimal cytotoxicity. Our results suggest the possibility that cytotoxicity induced by lipofection, accompanied by gene changes, could intrinsically exacerbate, attenuate or even mask the desired effects of gene-based therapy.

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“…Currently, delivery systems for gene transfer are generally classified as viral and non-viral vectors. Non-viral vectors have many advantages over viral vectors, such as calcium phosphate, liposome, and emerging chitosan (38)(39)(40)(41)(42)(43). In our study, a novel nonviral gene delivery system was developed based on PEI.…”

Section: Discussionmentioning

confidence: 99%

Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels

Yang

Gou²,

Deng³

et al. 2012

Oncology Reports

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Abstract. Currently, great interest is focused on the antineoplastic effects of CXC chemokine ligand 10 (IP-10/CXCL10). IP-10 has shown significant antitumor and anti-metastatic properties via immunological, antiangiogenic and anti-neoplastic mechanisms. However, very few studies on the antitumor activity of IP-10 in human ovarian cancer have been reported. The use of polymeric nanoparticles to deliver functional genes intraperitoneally holds much promise as an effective therapy for ovarian cancer. In our study, a recombinant plasmid expressing IP-10 (pVITRO-IP-10) was constructed, and biodegradable cationic heparin-polyethyleneimine (HPEI) nanogels were prepared to deliver pVITRO-IP-10 into SKOV3 human ovarian cancer cells. Transfection efficiency was detected by expression profiling of green fluorescent protein. The expression of IP-10 was determined using RT-PCR and western blot analysis. In vitro, cell proliferation was evaluated by MTT assay. Apoptosis was examined by Hoechst33258/PI staining and flow cytometry assays. The effect on the inhibition of angiogenesis was evaluated by tube formation assay using human umbilical vein endothelial cells (HUVECs). Moreover, a SKOV3 intraperitoneal ovarian carcinomatosis model was established to investigate the antitumor activity of HPEI+pVITRO-IP-10 complexes in nude mice. Tumor weights were evaluated during the treatment course. Cell proliferation and apoptosis were evaluated by Ki-67 immunochemical staining and TUNEL assay, and the antiangiogenic effect of pVITRO-IP-10 was assessed by CD31 immunochemical staining and alginate-encapsulated tumor cell assay. pVITRO-IP-10 was efficiently transfected into SKOV3 cells by HPEI nanogels. Intraperitoneal administration of HPEI+pVITRO-IP-10 complexes led to effective growth inhibition of ovarian cancer, in which tumor weight decreased by ~69.92% in the treatment group compared with that in the empty vector control group. Meanwhile, decreased cell proliferation, increased tumor cell apoptosis and reduction in angiogenesis were observed in the HPEI+pVITRO-IP-10 group compared with those in the control groups. These results indicated that HPEI nanogel delivery of pVITRO-IP-10 may be of value in the treatment against human ovarian cancer.

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Cationic lipid–DNA complexes—lipoplexes—for gene transfer and therapy

Cited by 161 publications

References 83 publications

The structural diversity of DNA–neutral phospholipids–divalent metal cations aggregates: a small-angle synchrotron X-ray diffraction study

The structural diversity of DNA–neutral phospholipids–divalent metal cations aggregates: a small-angle synchrotron X-ray diffraction study

Complex Formation with Plasmid DNA Increases the Cytotoxicity of Cationic Liposomes

Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels

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