Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection

• Published in: International journal of molecular sciences 2019-01, Vol.20 (2), p.430
• Main Authors: Nagase, Kenichi, Hasegawa, Momoko, Ayano, Eri, Maitani, Yoshie, Kanazawa, Hideko
• Format: Article
• Language: English
• Subjects: Acids; Aggregates; Cell Line; Cell Survival; Gene Expression; Gene Silencing; Genes, Reporter; Humans; Liposomes; Liposomes - chemistry; Magnetic Resonance Spectroscopy; Molecular Structure; Molecular Weight; Phase Transition; Phase transitions; Polyethylene glycol; Polymers; Polymers - chemistry; RNA Interference; RNA, Small Interfering - genetics; siRNA; Temperature; Thermodynamics; Transfection; Transfection - methods
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20020430

Small interfering RNAs (siRNAs) have been attracting significant attention owing to their gene silencing properties, which can be utilized to treat intractable diseases. In this study, two temperature-responsive liposomal siRNA carriers were prepared by modifying liposomes with different polymers-poly( -isopropylacrylamide- - , -dimethylaminopropyl acrylamide) (P(NIPAAm- -DMAPAAm)) and poly( -isopropylacrylamide- - , -dimethylacrylamide) P(NIPAAm- -DMAAm). The phase transition of P(NIPAAm- -DMAPAAm) was sharper than that of P(NIPAAm- -DMAAm), which is attributed to the lower co-monomer content. The temperature dependent fixed aqueous layer thickness (FALT) of the prepared liposomes indicated that modifying liposomes with P(NIPAAm- -DMAPAAm) led to a significant change in the thickness of the fixed aqueous monolayer between 37 °C and 42 °C; while P(NIPAAm- -DMAAm) modification led to FALT changes over a broader temperature range. The temperature-responsive liposomes exhibited cellular uptake at 42 °C, but were not taken up by cells at 37 °C. This is likely because the thermoresponsive hydrophilic/hydrophobic changes at the liposome surface induced temperature-responsive cellular uptake. Additionally, siRNA transfection of cells for the prevention of luciferase and vascular endothelial growth factor (VEGF) expression was modulated by external temperature changes. P(NIPAAm- -DMAPAAm) modified liposomes in particular exhibited effective siRNA transfection properties with low cytotoxicity compared with P(NIPAAm- -DMAAm) modified analogues. These results indicated that the prepared temperature-responsive liposomes could be used as effective siRNA carriers whose transfection properties can be modulated by temperature.