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Dual signal-responsive liposomes for temperature-controlled cytoplasmic delivery.

Bioconjugate chemistry (2011-08-24)
Tomohiro Kaiden, Eiji Yuba, Atsushi Harada, Yuichi Sakanishi, Kenji Kono
ABSTRACT

For production of a new type of functional liposome whose destabilization can be triggered by a combination of a temperature signal and acidic pH signal, we prepared liposomes modified with hyperbranched poly(glycidol) derivatives having N-isopropylamide and carboxyl groups. HeLa cells incubated with the dual signal-responsive liposomes encapsulating a water-soluble fluorescent dye pyranine at 28 °C displayed punctate fluorescence of pyranine, indicating that the liposomes were trapped in endosome. However, after heating at 45 °C for 15 min, the same cells exhibited diffuse fluorescence of pyranine, indicating that destabilization of the liposomes in endosome with an acidic environment in combination with the brief heating caused efficient transfer of the contents into cytosol. The dual signal-responsive liposomes might have usefulness for site-specific delivery of membrane-impermeable molecules, which exhibit bioactivities in the intracellular spaces, such as siRNA and proteins.

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Sigma-Aldrich
8-Hydroxypyrene-1,3,6-trisulfonic acid trisodium salt, ≥96%