کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10228922 | 498 | 2013 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Hsp90-targeted miRNA-liposomal formulation for systemic antitumor effect
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی شیمی
بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Chaperone protein Hsp90 maintains functional integrity and maturation of a large number of cellular proteins including transcription factors, kinases, etc. It is often over-expressed in cancer cells for simultaneous maintenance of many non-regulated and/or genetically mutated proteins. Small molecule-based regimens inhibiting over-expressing Hsp90 in cancer cells often plagued with improper targeting leading to non-specific toxicity. Recently using a glucocorticoid receptor (GR)-targeted cationic lipoplex, we observed cancer cell-specific GR-transactivation and transgene expression by utilizing an unprecedentedly compromised chaperone-activity of cancer cell-associated Hsp90. In normal cells, GR is expressed ubiquitously and is highly regulated and chaperoned by Hsp90. This does not allow cancer cell-alike GR-mediated transgene expression. As a novel anticancer strategy, we showed that compromising Hsp90 in cancer cells can be utilized to selectively deplete its own level by delivering a specially designed artificial miRNA-plasmid against Hsp90 (amiR-Hsp90). Practically, GR-mediated delivery of amiR-Hsp90 plasmid in tumor-bearing mice, depleted Hsp90, critically down-regulated levels of Akt, VEGFR2 and other Hsp90-client proteins but up-regulated wild-type p53 in tumor. These enforced apoptosis in angiogenic vessels and in tumor mass and significantly shrunk tumor-volume. The present study describes gene therapy strategy against Hsp90 using a new GR-targeted liposome-amiR-Hsp90 lipoplex formulation for treating cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 34, Issue 28, September 2013, Pages 6804-6817
Journal: Biomaterials - Volume 34, Issue 28, September 2013, Pages 6804-6817
نویسندگان
Subrata Kumar Pore, Ashwani Choudhary, Bhowmira Rathore, Anirban Ganguly, Pombala Sujitha, C. Ganesh Kumar, Sachin Bharat Agawane, Jerald Mahesh Kumar, Vinod Scaria, Beena Pillai, Rajkumar Banerjee,