کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5433387 1508987 2017 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Polymeric nanoparticles as cancer-specific DNA delivery vectors to human hepatocellular carcinoma
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Polymeric nanoparticles as cancer-specific DNA delivery vectors to human hepatocellular carcinoma
چکیده انگلیسی

Hepatocellular carcinoma (HCC) is the third most deadly cancer in the US, with a meager 5-year survival rate of < 20%. Such unfavorable numbers are closely related to the heterogeneity of the disease and the unsatisfactory therapies currently used to manage patients with invasive HCC. Outside of the clinic, gene therapy research is evolving to overcome the poor responses and toxicity associated with standard treatments. The inadequacy of gene delivery vectors, including poor intracellular delivery and cell specificity, are major barriers in the gene therapy field. Herein, we described a non-viral strategy for effective and cancer-specific DNA delivery to human HCC using biodegradable poly(beta-amino ester) (PBAE) nanoparticles (NPs). Varied PBAE NP formulations were evaluated for transfection efficacy and cytotoxicity to a range of human HCC cells as well as healthy human hepatocytes. To address HCC heterogeneity, nine different sources of human HCC cells were utilized. The polymeric NPs composed of 2-((3-aminopropyl)amino) ethanol end-modified poly(1,5-pentanediol diacrylate-co-3-amino-1-propanol) ('536') at a 25 polymer-to-DNA weight-to-weight ratio led to high transfection efficacy to all of the liver cancer lines, but not to hepatocytes. Each individual HCC line had a significantly higher percentage of exogenous gene expression than the healthy liver cells (P < 0.01). Notably, this biodegradable end-modified PBAE gene delivery vector was not cytotoxic and maintained the viability of hepatocytes above 80%. In a HCC/hepatocyte co-culture model, in which cancerous and healthy cells share the same micro-environment, 536 25 w/w NPs specifically transfected cancer cells. PBAE NP administration to a subcutaneous HCC mouse model, established with one of the human lines tested in vitro, confirmed effective DNA transfection in vivo. PBAE-based NPs enabled high and preferential DNA delivery to HCC cells, sparing healthy hepatocytes. These biodegradable and liver cancer-selective NPs are a promising technology to deliver therapeutic genes to liver cancer.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 263, 10 October 2017, Pages 18-28
نویسندگان
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