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2 results on '"albumin-associated lipoplexes"'

1. MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer

Author

Henrique Faneca, Maria C. Pedroso de Lima, and Marta Passadouro

Subjects
delivery nanosystems, Indoles, Cell Survival, Biophysics, Pharmaceutical Science, Bioengineering, Antineoplastic Agents, Biology, Transfection, Biomaterials, International Journal of Nanomedicine, Pancreatic cancer, Cell Line, Tumor, Drug Discovery, microRNA, medicine, Sunitinib, Gene silencing, Humans, Pyrroles, Gene, Original Research, Oligonucleotide, Organic Chemistry, Cancer, Drug Synergism, General Medicine, Genetic Therapy, Oligonucleotides, Antisense, medicine.disease, Molecular biology, 3. Good health, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, MicroRNAs, pancreatic cancer gene therapy, Cancer research, Phosphatidylcholines, albumin-associated lipoplexes, anti-microRNAs oligonucleotides, medicine.drug, Carcinoma, Pancreatic Ductal
Abstract

Marta Passadouro,1,2 Maria C Pedroso de Lima,1,2 Henrique Faneca11Center for Neuroscience and Cell Biology, 2Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, PortugalAbstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and mortal cancer, characterized by a set of known mutations, invasive features, and aberrant microRNA expression that have been associated with hallmark malignant properties of PDAC. The lack of effective PDAC treatment options prompted us to investigate whether microRNAs would constitute promising therapeutic targets toward the generation of a gene therapy approach with clinical significance for this disease. In this work, we show that the developed human serum albumin–1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine:cholesterol/anti-microRNA oligonucleotides (+/–) (4/1) nanosystem exhibits the ability to efficiently deliver anti-microRNA oligonucleotides targeting the overexpressed microRNAs miR-21, miR-221, miR-222, and miR-10in PDCA cells, promoting an almost complete abolishment of microRNA expression. Silencing of these microRNAs resulted in a significant increase in the levels of their targets. Moreover, the combination of microRNA silencing, namely miR-21, with low amounts of the chemotherapeutic drug sunitinib resulted in a strong and synergistic antitumor effect, showing that this combined strategy could be of great importance for therapeutic application in PDAC. Keywords: pancreatic cancer gene therapy, anti-microRNAs oligonucleotides, delivery nanosystems, albumin-associated lipoplexes

Published
2014

2. MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer.

Author

Passadouro M, Pedroso de Lima MC, and Faneca H

Subjects
Carcinoma, Pancreatic Ductal metabolism, Cell Line, Tumor, Cell Survival drug effects, Drug Synergism, Genetic Therapy methods, Humans, Oligonucleotides, Antisense genetics, Pancreatic Neoplasms metabolism, Phosphatidylcholines, Sunitinib, Transfection methods, Antineoplastic Agents pharmacology, Carcinoma, Pancreatic Ductal genetics, Gene Expression Regulation, Neoplastic drug effects, Indoles pharmacology, MicroRNAs genetics, Pancreatic Neoplasms genetics, Pyrroles pharmacology
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and mortal cancer, characterized by a set of known mutations, invasive features, and aberrant microRNA expression that have been associated with hallmark malignant properties of PDAC. The lack of effective PDAC treatment options prompted us to investigate whether microRNAs would constitute promising therapeutic targets toward the generation of a gene therapy approach with clinical significance for this disease. In this work, we show that the developed human serum albumin-1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine:cholesterol/anti-microRNA oligonucleotides (+/-) (4/1) nanosystem exhibits the ability to efficiently deliver anti-microRNA oligonucleotides targeting the overexpressed microRNAs miR-21, miR-221, miR-222, and miR-10 in PDCA cells, promoting an almost complete abolishment of microRNA expression. Silencing of these microRNAs resulted in a significant increase in the levels of their targets. Moreover, the combination of microRNA silencing, namely miR-21, with low amounts of the chemotherapeutic drug sunitinib resulted in a strong and synergistic antitumor effect, showing that this combined strategy could be of great importance for therapeutic application in PDAC.

Published
2014
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