We report the encapsulation of the hydrophilic model molecule calcein in the Zr-based MOF UiO-66, followed by amorphization of the framework by ball-milling. We show controlled release of calcein over more than 30 days, compared with the 2 day release period from crystalline UiO-66.
AbstractpH-responsive polymers have been synthesised by grafting L-valine , L-leucine and L-phenylalanine onto the pendant carboxylic acid moieties of a pseudo-peptide, poly(Llysine iso-phthalamide), at a stoichiometric degree of substitution of 75 mol%. The effect of such modification on the pH-, concentration-and time-dependent cell membrane-disruptive activity of the grafted polymers has been investigated using a haemolysis model. At 0.025 mg mL −1 , the grafted polymers were almost non-haemolytic at pH 7.4, but mediated considerable membrane lysis after 60 min in the pH range characteristic of early endosomes, which ranked in the order: PP-75 > PL-75 > PV-75 > poly(L-lysine iso-phthalamide). PP-75 was 35-fold more lytic on a molar basis than the membrane-lytic peptide melittin. With increasing concentration, the grafted polymers showed an increased ability to lyse cell membranes and caused noticeable membrane disruption at physiological pH. The mechanism of the polymer-mediated membrane destabilisation has been investigated. The in-vitro cytotoxicity of the grafted polymers has been assessed using a propidium iodide fluorescence assay. It has been demonstrated by confocal microscopy that the grafted polymers can induce a significant release of endocytosed materials into the cytoplasm of HeLa cells, which is a feature critical for drug delivery applications.
Pseudo-peptidic polymers have been synthesised by grafting L-valine (PV), L-leucine (PL) and L-phenylalanine (PP) onto the pendant carboxylic acid moieties of a pH-responsive polyamide, poly(L-lysine isophthalamide). The pH-responsive aqueous solution properties of PV-75, PL-75 and PP-75 with a stoichiometric degree of substitution of 75 mol% have been compared with those of the parent poly(L-lysine isophthalamide) using UV-visible and fluorescence spectroscopy. At low concentrations (#0.1 mg mL À1 ), the grafted polymers displayed pH-dependent conformation. The pH at the onset of hydrophobic association (pH h ) and the pH range over which association occurred varied significantly between the different amino acid grafts. The pH h values of PV-75, PL-75 and PP-75 at 0.025 mg mL À1 were 6.2, 7.0 and 7.2, respectively. Increasing concentration enhanced intermolecular aggregation. A bis-functional Cy5 derivative, incorporated within the backbones of poly(L-lysine isophthalamide) (polyCy5) and PP-75 (PDP-75), was demonstrated to act as a fluorescence reporter on the state of polymer conformation and aggregation. The intracellular trafficking of PDP-75, examined by confocal microscopy, indicates potential applications of the grafted polymers in drug delivery and medical imaging.
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