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Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA
Kenichi Nagase1, Momoko Hasegawa2, Eri Ayano3
1Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato, Tokyo 105-8512, Japan. nagase-kn@pha.keio.ac.jp.
International Journal of Molecular Sciences
|January 24, 2019
Summary
Temperature-responsive liposomes effectively deliver small interfering RNAs (siRNAs) for gene silencing. These novel carriers show enhanced cellular uptake and siRNA transfection at 42°C, offering a promising therapeutic approach for intractable diseases.
Area of Science:
- Biotechnology and Nanomedicine
- Polymer Chemistry
- Gene Therapy
Background:
- Small interfering RNAs (siRNAs) are potent tools for gene silencing with therapeutic potential for intractable diseases.
- Developing effective and controllable delivery systems for siRNAs remains a critical challenge in gene therapy.
- Temperature-responsive materials offer a unique mechanism for triggered drug/nucleic acid delivery.
Purpose of the Study:
- To design and characterize novel temperature-responsive liposomal carriers for siRNA delivery.
- To investigate the influence of polymer modification on liposome properties and temperature-dependent behavior.
- To evaluate the efficacy and safety of these liposomes for siRNA transfection modulated by temperature.
Main Methods:
- Synthesis of two distinct temperature-responsive polymers: P(NIPAAm-co-DMAPAAm) and P(NIPAAm-co-DMAAm).
- Modification of liposomes with these polymers to create temperature-responsive carriers.
- Characterization of polymer phase transition, liposome fixed aqueous layer thickness (FALT), cellular uptake, and siRNA transfection efficiency at different temperatures (37°C vs. 42°C).
Main Results:
- P(NIPAAm-co-DMAPAAm) exhibited a sharper phase transition and induced significant FALT changes between 37°C and 42°C compared to P(NIPAAm-co-DMAAm).
- Liposomes demonstrated temperature-responsive cellular uptake, occurring at 42°C but not at 37°C, due to surface hydrophilic/hydrophobic changes.
- siRNA transfection for luciferase and VEGF gene silencing was effectively modulated by temperature, with P(NIPAAm-co-DMAPAAm) modified liposomes showing superior transfection and low cytotoxicity.
Conclusions:
- The developed temperature-responsive liposomes serve as effective siRNA carriers with externally controllable transfection properties.
- P(NIPAAm-co-DMAPAAm) modified liposomes demonstrate enhanced performance and reduced cytotoxicity, highlighting their potential in gene therapy.
- Temperature modulation offers a promising strategy to control siRNA delivery and gene silencing efficacy.
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