한빛사논문
KAIST
Bon Il Koo1,†, Dong Jae Lee1,†, Rafia Tasnim Rahman1, and Yoon Sung Nam1,2,*
1Department of Materials Science and Engineering and
2Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
†These authors equally contributed to this work.
*To whom correspondence should be addressed : Yoon Sung Nam
Abstract
Lipid vesicles have been widely used for drug and gene delivery, but their structural instability reduces in vivo efficacy and requires specialized handling for transport and storage. To address these limitations, strategies like lipid cross-linking and polymer-lipid conjugation have been suggested to bolster vesicle stability and improve biological efficacy. However, the in vivo metabolism of the chemically altered lipids remains unclear, prompting a need for extensive studies for their practical applications. Accordingly, a new stabilization technique without chemical modification is in urgent demand. Here, we present a bio-mimetic approach for fabricating robust multilamellar lipid vesicles, which substantially enhance the in vivo delivery and stabilization of protein antigens. Our new method leverages 1-O-acylceramide, a lipid naturally present in the skin, to facilitate the self-assembly of lipid nanovesicles. The incorporation of 1-O-acylceramide, which acts to anchor lipid bilayers akin to its role in the stratum corneum, confers excellent stability to the multilamellar vesicles under environmental stresses, including repeated freeze-thaw cycles. The encapsulation of ovalbumin as a model antigen and the adjuvant monophosphoryl lipid A demonstrates the hybrid vesicle's potential as a nanovaccine platform. In vitro cell studies show that both unilamellar and multilamellar vesicles enhance immune responses, but in vivo analyses distinguish the multilamellar vesicles as notably more efficient in inducing higher levels of antibody and cytokine secretion. This work suggests the ceramide-induced multilamellar lipid vesicles as an effective nanovaccine platform, promising enhanced antigen delivery and stability for improved in vivo antigen cross-presentation.
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