Lipid–peptide bioconjugation through pyridyl disulfide reaction chemistry and its application in cell targeting and drug delivery

Journal of Nanobiotechnology

卷:17

Ajay K. Monnappa¹  Paolo Natale²  Diego de la Fuente-Herreruela²  Eduardo Enciso²  Aarón Morallón-Piña²  Iván López-Montero²  Luis Sánchez³  Fabrice Giusti⁴  Mónica Muñoz-Úbeda⁵ 

[1] Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST);

[2] Dto. Química Física, Universidad Complutense de Madrid;

[3] Dto. Química Orgánica, Universidad Complutense de Madrid;

[4] Institut de Chimie Séparative de Marcoule, ICSM, UMR 5257;

[5] Instituto de Investigación Hospital Doce de Octubre (i+12);

关键词: Smart liposomes;    Disulfide bonds;    Targeting peptide;    GALA;    Endosomal escape;   

DOI  :  10.1186/s12951-019-0509-8

来源: DOAJ

【 摘 要 】

Abstract Background The design of efficient drug delivery vectors requires versatile formulations able to simultaneously direct a multitude of molecular targets and to bypass the endosomal recycling pathway of cells. Liposomal-based vectors need the decoration of the lipid surface with specific peptides to fulfill the functional requirements. The unspecific binding of peptides to the lipid surface is often accompanied with uncontrolled formulations and thus preventing the molecular mechanisms of a successful therapy. Results We present a simple synthesis pathway to anchor cysteine-terminal peptides to thiol-reactive lipids for adequate and quantitative liposomal formulations. As a proof of concept, we have synthesized two different lipopeptides based on (a) the truncated Fibroblast Growth Factor (tbFGF) for cell targeting and (b) the pH sensitive and fusogenic GALA peptide for endosomal scape. Conclusions The incorporation of these two lipopeptides in the liposomal formulation improves the fibroblast cell targeting and promotes the direct delivery of cargo molecules to the cytoplasm of the cell.

【 授权许可】

Unknown