| abstract |
The invention relates to a cationic thermosensitive liposome modified by a cell-penetrating peptide and a preparation method thereof. The present invention is mainly used for the encapsulation and delivery of nucleic acids such as siRNA, mRNA and DNA. Among them, using the characteristics of heat-sensitive liposomes, the storage stability at room temperature and 4 °C is good, and the fluidity of the liposome membrane at the in vivo ambient temperature (37.5 °C) increases, and the liposomes mainly deliver the encapsulated material directly to the cytoplasm by membrane fusion. , avoid the endocytosis-lysosomal pathway, thereby protecting the integrity and spatial structure of the active substance, and improving the intracellular delivery efficiency; the present invention utilizes a cell-penetrating peptide-sterol conjugate to play the dual role of cholesterol and cation, replacing cholesterol, And reducing the amount of cationic lipid material, on the one hand, the liposome is modified to make it positively charged, thereby facilitating the encapsulation of negatively charged active ingredients, and on the other hand, the cell-penetrating peptide-sterol conjugate is metabolized in the body. It is a non-toxic amino acid with significantly reduced toxicity compared to cationic lipids with quaternary ammonium head structures. The cell-penetrating peptide-modified nucleic acid-cationic thermosensitive liposome disclosed in the present invention can be applied to the field of biomedicine. |