Systemic delivery of E6/7 siRNA using novel lipidic particles and its application with cisplatin in cervical cancer mouse models
| Autor: | Nigel A.J. McMillan, Akul Singhania, Sherry Y. Wu, Nigel M. Davies, Lisa N. Putral, Carl M. J. Kirkpatrick, Melinda Burgess |
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| Rok vydání: | 2010 |
| Předmět: |
Small interfering RNA
Pathology medicine.medical_specialty Genetic enhancement Papillomavirus E7 Proteins Uterine Cervical Neoplasms Antineoplastic Agents Cervix Uteri Transfection Mice In vivo Neoplasms Genetics medicine Gene silencing Animals Gene Silencing RNA Small Interfering Molecular Biology Cisplatin Gene knockdown business.industry Cancer Oncogene Proteins Viral medicine.disease Combined Modality Therapy Lipids Mice Inbred C57BL Repressor Proteins Cancer research Molecular Medicine Female business medicine.drug |
| Zdroj: | Gene therapy. 18(1) |
| ISSN: | 1476-5462 |
| Popis: | Small interfering RNA (siRNA) shows great promise in cancer therapy, but its effectiveness in vivo still remains a crucial issue for its transition into the clinics. Although the successful use of polyethylene glycol (PEG)ylated lipidic delivery systems have already been reported, most of the formulation procedures used are labour intensive and also result in unstable end products. We have previously developed a simple yet efficient hydration-of-freeze-dried-matrix (HFDM) method to entrap siRNA within lipid particles, in which the products exhibited superior stability. Here, we show that these HFDM-formulated particles are stable in the presence of serum and can deliver siRNA efficiently to tumours after intravenous administration. Using these particles, around 50% knockdown of the target gene expression was observed in tumours. With the use of siRNA targeting the E6/7 oncogenes expressed in cervical cancer, we showed a 50% reduction in tumour size. This level of tumour growth suppression was comparable to that achieved from cisplatin at the clinically used dose. Overall, our results demonstrate the feasibility of using HFDM-formulated particles to systematically administer E6/7-targeted siRNA for cervical cancer treatment. The simplicity of preparation procedure along with superior product stability obtained from our method offers an innovative approach for the in vivo delivery of siRNA. |
| Databáze: | OpenAIRE |
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