Abstract:
:Developments in the field of molecular oncology have revealed that resistance to chemotherapeutics is acqured through several mechanisms including overexpression of common oncogenic proteins. Signal Transducer and Activator of Transcription 3 (STAT3) is one of these oncogenes that is overexpressed in many cancer types. RNA interference (RNAi) is proven powerful tool for downregulating STAT3, allowing re-sensitization of resistant cancer cells. However, delivery of RNA interference-mediating molecules for STAT3 downregulation in lung cancer cells is limited to a small number of studies most of which employ commercially available transfection kits. The aim of this study was to develop and evaluate cationic solid lipid nanoparticles for delivery of RNAi-mediating plasmid DNA in order to down regulate STAT3 in cisplatin resistant lung cancer cells. We focused on obtaining cSLN:plasmid DNA complexes with size below or equal to 100nm, and a positive zeta potential. Two successful candidate cSLN:plasmid DNA complexes (K2 and K3) were selected for in vitro tests and cell culture studies. These formulations have particle sizes of 98 and 93nm, and zeta potential values of 10.5 and 8.9mV, respectively. Plasmid DNA in these complexes was protected against DNaseI and serum-mediated degradation. Substantial part of DNA retained its supercoiled and circular conformation. TEM images showed nearly spherical complex structure. Both formulations reduced STAT3 expression by approx. 5-fold in cisplatin resistant Calu1 cell line and increased the sensitivity of cells to cisplatin.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Kotmakçı M,Çetintaş VB,Kantarcı AGdoi
10.1016/j.ijpharm.2017.04.034subject
Has Abstractpub_date
2017-06-15 00:00:00pages
101-111issue
1eissn
0378-5173issn
1873-3476pii
S0378-5173(17)30324-1journal_volume
525pub_type
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