Nuclear translocation of human H‐chain in its intact cage‐like structure without any additional modifications enables a rapid nuclear delivery of an encapsulated anticancer drug (doxorubicin). This reduces the doses of drugs simultaneously bypassing the cellular multidrug resistance. Apoferritin exhibits synergistic effects through attenuating drug‐induced dysregulation of the cellular iron. Tests on cerebellar organotypic cultures show the natural cell selectivity and drug accumulation in brain tissue.
Selective addressing of membrane components in complex membrane mixtures is important for many biological processes. The present paper investigates the recognition between multivalent surface functionalized nanoparticles (NPs) and amphiphilic block copolymers (BCPs), which are successfully incorporated into lipid membranes. The concept involves the supramolecular recognition between hybrid membranes (composed of a mixture of a lipid (DPPC or DOPC), an amphiphilic triazine-functionalized block copolymer TRI-PEO13-b-PIB83 (BCP 2), and nonfunctionalized BCPs (PEO17-b-PIB87 BCP 1)) with multivalent (water-soluble) nanoparticles able to recognize the triazine end group of the BCP 2 at the membrane surface via supramolecular hydrogen bonds. CdSe-NPs bearing long PEO47-thymine (THY) polymer chains on their surface specifically interacted with the 2,4-diaminotriazine (TRI) moiety of BCP 2 embedded within hybrid lipid/BCP mono- or bilayers. Experiments with GUVs from a mixture of DPPC/BCP 2 confirm selective supramolecular recognition between the THY-functionalized NPs and the TRI-functionalized polymers, finally resulting in the selective removal of BCP 2 from the hybrid vesicle membrane as proven via facetation of the originally round and smooth vesicles. GUVs (composed of DOPC/BCP 2) show that a selective removal of the polymer component from the fluid hybrid membrane results in destruction of hybrid vesicles via membrane rupture. Adsorption experiments with mixed monolayers from lipids with either BCP 2 or BCP 1 (nonfunctionalized) reveal that the THY-functionalized NPs specifically recognize BCP 2 at the air/water interface by inducing significantly higher changes in the surface pressure when compared to monolayers from nonspecifically interacting lipid/BCP 1 mixtures. Thus, recognition of multivalent NPs with specific membrane components of hybrid lipid/BCP mono- and bilayers proves the selective removal of BCPs from mixed membranes, in turn inducing membrane rupture. Such recognition events display high potential in controlling permeability and fluidity of membranes (e.g., in pharmaceutics).
Biocompatible, highly water-soluble, nonionic, amphiphilic block copolymers having different hydrophobic blocks and architectures, but similar molecular size and chemical nature of the hydrophilic blocks, were investigated to check for their ability to form hybrid giant unilamellar vesicles with proteins, and for their interactions with giant unilamellar phospholipid vesicles (GUV). PGM14-b-PPO34-b-PGM14 (PGM-PPO-PGM) consists of a poly(propylene oxide) middle block and outer poly(glycerol monomethacrylate) blocks. Ch-PEG32-b-IPG18 (Ch-PEG-IPG) and Ch-PEG30-b-hbPG17 (Ch-PEG-hbPG) have a linear poly(ethylene glycol) block, linked to a cholesterol end group and to a linear (IPG) or hyperbranched (hbPG) polyglycerol block. Fluorescently-labelled polymers were synthesised to image and analyse the self-assembling and interaction processes using confocal laser scanning microscopy (CLSM). By implementing a novel strategy for polymersomes formation the copolymers were found to spontaneously form giant unilamellar vesicles with proteins in aqueous solution. Furthermore, the investigation of the interaction of the block copolymers with different phospholipid GUVs provided detailed information about the structure-behaviour relationship. Additionally, it was found that these neutral copolymers are able to cross artificial and natural phospholipid membranes.
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