Open AccessBiodegradable and Dual‐Responsive Polypeptide‐Shelled Cyclodextrin‐Containers for Intracellular Delivery of Membrane‐Impermeable Cargo
Author(s) -
Kudruk Sergej,
Pottanam Chali Sharafudheen,
Linard Matos Anna Livia,
Bourque Cole,
Dunker Clara,
Gatsogiannis Christos,
Ravoo Bart Jan,
Gerke Volker
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202100694
Subject(s) - endosome , cytosol , membrane , chemistry , vesicle , amphiphile , biophysics , intracellular , peptide , endocytosis , biochemistry , cell , microbiology and biotechnology , biology , organic chemistry , copolymer , enzyme , polymer
The transport of membrane impermeable compounds into cells is a prerequisite for the efficient cellular delivery of hydrophilic and amphiphilic compounds and drugs. Transport into the cell's cytosolic compartment should ideally be controllable and it should involve biologically compatible and degradable vehicles. Addressing these challenges, nanocontainers based on cyclodextrin amphiphiles that are stabilized by a biodegradable peptide shell are developed and their potential to deliver fluorescently labeled cargo into human cells is analyzed. Host–guest mediated self‐assembly of a thiol‐containing short peptide or a cystamine‐cross‐linked polypeptide shell on cyclodextrin vesicles produce short peptide‐shelled (SPSV ss ) or polypeptide‐shelled vesicles (PPSV ss ), respectively, with redox‐responsive and biodegradable features. Whereas SPSV ss are permeable and less stable, PPSV ss effectively encapsulate cargo and show a strictly regulated release of membrane impermeable cargo triggered by either reducing conditions or peptidase treatment. Live cell experiments reveal that the novel PPSV SS are readily internalized by primary human endothelial cells (human umbilical vein endothelial cells) and cervical cancer cells and that the reductive microenvironment of the cells’ endosomes trigger release of the hydrophilic cargo into the cytosol. Thus, PPSV SS represent a highly efficient, biodegradable, and tunable system for overcoming the plasma membrane as a natural barrier for membrane‐impermeable cargo.