Bio-inspired pulmonary surfactant-modified nanogels: A promising siRNA delivery system

Journal of Controlled Release : Official Journal of the Controlled Release Society
Lynn De BackerK Raemdonck

Abstract

Inhalation therapy with small interfering RNA (siRNA) is a promising approach in the treatment of pulmonary disorders. However, clinical translation is severely limited by the lack of suitable delivery platforms. In this study, we aim to address this limitation by designing a novel bioinspired hybrid nanoparticle with a core-shell nanoarchitecture, consisting of a siRNA-loaded dextran nanogel (siNG) core and a pulmonary surfactant (Curosurf®) outer shell. The decoration of siNGs with a surfactant shell enhances the colloidal stability and prevents siRNA release in the presence of competing polyanions, which are abundantly present in biofluids. Additionally, the impact of the surfactant shell on the biological efficacy of the siNGs is determined in lung cancer cells. The presence of the surfactants substantially reduces the cellular uptake of siNGs. Remarkably, the lowered intracellular dose does not impede the gene silencing effect, suggesting a crucial role of the pulmonary surfactant in the intracellular processing of the nanoparticles. In order to surmount the observed reduction in cellular dose, folate is incorporated as a targeting ligand in the pulmonary surfactant shell to incite receptor-mediated endocytosis. The latter...Continue Reading

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Citations

Sep 13, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lynn De BackerKoen Raemdonck
Aug 27, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lynn De BackerKoen Raemdonck
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