Intracellular protein delivery is highly desirable for protein drug-based cell therapy. Established technologies suffer from poor cell-specific cytosolic protein delivery, which hampers the targeting therapy of specific cell populations. A fusogenic liposome system enables cytosolic delivery, but its ability of cell-specific and controllable delivery is quite limited. Inspired by the kinetics of viral fusion, we designed a phosphorothioated DNA coatings-modified fusogenic liposome to mimic the function of viral hemagglutinin. The macromolecular fusion machine docks cargo-loaded liposomes at the membrane of target cells, triggers membrane fusion upon pH or UV light stimuli, and facilitates cytosolic protein delivery. Our results showed efficient cell-targeted delivery of proteins of various sizes and charges, indicating the phosphorothioated DNA plug-in unit on liposomes could be a general strategy for spatial-temporally controllable protein delivery both in vitro and in vivo.
Keyphrases
- cell therapy
- single cell
- drug delivery
- crispr cas
- genome editing
- sars cov
- mesenchymal stem cells
- protein protein
- cancer therapy
- amino acid
- single molecule
- circulating tumor
- machine learning
- cell proliferation
- small molecule
- bone marrow
- deep learning
- high throughput
- cell death
- cell free
- smoking cessation
- drug induced
- circulating tumor cells
- adverse drug