Gene transfer by guanidinium-cholesterol: dioleoylphosphatidyl-ethanolamine liposome-DNA complexes in aerosol

Densmore, Charles L.; Giddings, Thomas H.; Waldrep, J. Clifford; Kinsey, Berma M.; Knight, Vernon

doi:10.1002/(sici)1521-2254(199907/08)1:4<251::aid-jgm43>3.0.co;2-z

Cited by 55 publications

(19 citation statements)

References 27 publications

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“…We have shown that PEI -DNA gene aerosol formulations are resistant to the shear forces of nebulization, a problem associated with many cationic lipid -based gene formulations 17 and, as a result, levels of expression were sufficient to result in a meaningful immune responses to the human growth hormone gene delivered in PEI -gene aerosol. 14 Tumor Index Figure 5.…”

Section: Discussionmentioning

confidence: 99%

Growth suppression of established human osteosarcoma lung metastases in mice by aerosol gene therapy with PEI– p53 complexes

et al. 2001

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Lung metastases are a frequent complication of osteosarcoma and a treatment that would reduce the severity of this complication would be of great benefit to patients. We have used a formulation consisting of polyethyleneimine ( PEI ) and a p53 gene administered in aerosol to treat established lung micrometastases as a model of human osteosarcoma in nude mice. The SAOS -LM6 cell line, a metastatic derivative of the p53 null SAOS -2 line, expresses high levels of p53 protein after in vitro transfection with PEI -p53 complexes as determined by ELISA, and transfection with both p53wt and the p53 variant, p53 -CD( 1 -366 ) in vitro, results in a marked inhibition of SAOS -LM6 cell proliferation. Aerosol delivery of plasmid DNA containing either the p53 gene or a p53 -CD( 1 -366 ) variant gene formulated with PEI to mice resulted in highly significant reductions in the numbers and size of tumors ( P < .001 ), the total number of tumor foci in the lungs ( P < .001 ) and the size of individual tumor nodules in treated animals compared to untreated, PEI only -treated and PEI -CAT -treated control animals. The different tissues examined did not reveal any signs of toxicity or inflammation after repeated exposure to PEI -DNA. The aerosol delivery of PEI -based formulations of p53 or synthetic p53 variant genes represents a promising new strategy for the treatment of established human osteosarcoma lung metastases. The noninvasive nature of aerosol delivery coupled with low toxicity also make this therapeutic approach potentially appropriate for combination therapy with either radio -or chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Growth suppression of established human osteosarcoma lung metastases in mice by aerosol gene therapy with PEI– p53 complexes

et al. 2001

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“…95 After first report of inhalation gene delivery success, 115 many reports have been published on gene delivery using cationic liposomes by pulmonary administration. 104,[116][117][118][119][120][121][122][123] Many recent reviews 95,124,125 present gene delivery system using cationic liposomes. Moreover, liposomes conjugated with cell-penetrating peptides are recognized as potential nanocarrier systems for intracellular delivery of macromolecules to the lung.…”

Section: Thrombosismentioning

confidence: 99%

Nanomedicine in pulmonary delivery

Mansour¹,

Rhee²,

Wu³

2009

IJN

409

269

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“…14 Lip + pCA -IL -12 were prepared at a lipid:DNA ratio of 6:1 by diluting the DNA in water and slowly adding it to the lipid dispersion while vortexing as described previously. 14 …”

Section: Reagentsmentioning

confidence: 99%

Eradication of osteosarcoma lung metastases following intranasal interleukin-12 gene therapy using a nonviral polyethylenimine vector

et al. 2002

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The use of adenoviral vectors for therapeutic delivery of genes via pulmonary application poses several problems in terms of immune responses. The purpose of this study was to determine whether polyethylenimine ( PEI ), a polycationic DNA carrier, can be used to deliver the IL -12 gene into the lungs of mice having microscopic osteosarcoma ( OS ) lung metastases. Incubation of SAOS -LM6 cells in vitro with PEI containing the murine IL -12 ( mIL -12 ) gene ( PEI:IL -12 ) resulted in expression of both the p35 and p40 subunits of IL -12 mRNA and production of mIL -12 protein. Using our newly developed OS nude mouse model, we demonstrated that treatment of mice using intranasal PEI:IL -12 resulted in significant IL -12 mRNA expression in the lung but not the liver. Furthermore, plasma IL -12 was undetectable after up to 4 weeks of intranasal PEI:IL -12 therapy given twice weekly. No IL -12 expression was seen following intranasal PEI therapy alone. The number of lung metastases in animals that received intranasal PEI:IL -12 twice weekly for 4 weeks starting 6 weeks after tumor inoculation was significantly decreased ( median, 11; range, 0 -47 ) compared with those that received PEI alone ( median, 89; range, 2 to >200; P = .012 ). Also, the size of the nodules was significantly smaller in the PEI:IL -12 -treated animals, with 90% measuring 0.5 mm in diameter compared with 56% in the PEI -alone group. Animals that received PEI alone also had numerous large nodules ( 3 -6 mm ) throughout the lungs. Intranasal therapy is a noninvasive way to administer agents and has the advantage of targeting the pulmonary region, resulting in higher concentrations in the tumor area. Additionally, delivery of IL -12 to the lung via the airway using PEI may avoid systemic toxicity. Because OS metastasizes almost exclusively to the lung, this may be a novel approach to the treatment of pulmonary OS metastases. Cancer Gene Therapy ( 2002 ) 9, 260 -266 DOI: 10.1038 / sj / cgt / 7700432Keywords: osteosarcoma; lung metastasis; PEI; IL -12; intranasal therapy D espite multiple changes in the adjuvant chemotherapy regimens used to treat osteosarcoma (OS ), the 2-year metastasis -free survival rate in patients having this disease has stagnated at 65 -70%. 1 -3 The majority of OS patients who have a relapse do so within the first year while receiving chemotherapy. In these patients, the lung is the most common site of metastatic spread. Those who initially present with metastatic lung disease have an even higher rate of treatment failure, as no more than 15% achieve long -term metastasis -free survival. Although the majority of OS patients having pulmonary metastases can be rendered disease-free using thoracic surgery, 80 -85% will have a relapse in the lung within 1 year; 4,5 salvage chemotherapy has been disappointing in improving this progression-free interval. This indicates that patients may benefit from new approaches and agents targeted specifically to pulmonary metastases.Our laboratory has recently developed an experimental OS lung me...

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Gene transfer by guanidinium-cholesterol: dioleoylphosphatidyl-ethanolamine liposome-DNA complexes in aerosol

Cited by 55 publications

References 27 publications

Growth suppression of established human osteosarcoma lung metastases in mice by aerosol gene therapy with PEI– p53 complexes

Growth suppression of established human osteosarcoma lung metastases in mice by aerosol gene therapy with PEI– p53 complexes

Nanomedicine in pulmonary delivery

Eradication of osteosarcoma lung metastases following intranasal interleukin-12 gene therapy using a nonviral polyethylenimine vector

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