ABSTRACT
Microbial adhesion to host cells represents the initial step in the infection process. Several methods have been explored to inhibit microbial adhesion including the use of glycopolymers based on mannose, galactose, sialic acid and glucose. These sugar receptors are, however, abundant in the body, and are not unique to bacteria. Trehalose, in contrast, is a unique disaccharide that is widely expressed by microbes. This carbohydrate has not yet been explored as an anti-adhesive agent. Herein, gold nanoparticles (AuNPs) coated with trehalose-based polymers were prepared and compared to glucose-functionalized AuNPs and examined for their ability to prevent binding to endothelial cells. Acting as anti-adhesive agents, trehalose-functionalized NPs decreased the binding of S.â aureus to HUVECs, while outperforming the control NPs. Microscopy revealed that trehalose-coated NPs bound strongly to S.â aureus compared to the controls. In conclusion, nanoparticles based on trehalose could be a non-toxic alternative to inhibit S.â aureus infection.
Subject(s)
Anti-Bacterial Agents/pharmacology , Glucose/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Staphylococcus aureus/drug effects , Trehalose/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Bacterial Adhesion/drug effects , Human Umbilical Vein Endothelial Cells , Humans , Staphylococcus aureus/physiologyABSTRACT
Soft materials in nature are formed through reversible supramolecular assembly of biological polymers into dynamic hierarchical networks. Rational design has led to self-assembling peptides with structural similarities to natural materials. However, recreating the dynamic functional properties inherent to natural systems remains challenging. Here we report the discovery of a short peptide based on the tryptophan zipper (trpzip) motif, that shows multiscale hierarchical ordering that leads to emergent dynamic properties. Trpzip hydrogels are antimicrobial and self-healing, with tunable viscoelasticity and unique yield-stress properties that allow immediate harvest of embedded cells through a flick of the wrist. This characteristic makes Trpzip hydrogels amenable to syringe extrusion, which we demonstrate with examples of cell delivery and bioprinting. Trpzip hydrogels display innate bioactivity, allowing propagation of human intestinal organoids with apical-basal polarization. Considering these extensive attributes, we anticipate the Trpzip motif will prove a versatile building block for supramolecular assembly of soft materials for biotechnology and medicine.
Subject(s)
Hydrogels , Tryptophan , Humans , Tryptophan/chemistry , Hydrogels/chemistry , Peptides/chemistry , Biotechnology , OrganoidsABSTRACT
Understanding cellular uptake and particle trafficking within the cells is essential for targeted drug delivery applications. Existing studies reveal that the geometrical aspects of nanocarriers, for example, shape and size, determine their cell uptake and sub-cellular transport pathways. However, considerable efforts have been directed toward understanding the cell uptake mechanism and trafficking of spherical particles. Detailed analysis on the uptake mechanism and downstream intracellular processing of non-spherical particles remains elusive. Here, we used polymeric two-dimensional platelets based on poly(ε-caprolactone) (PCL) prepared by living crystallization-driven self-assembly as a platform to investigate the cell uptake and intracellular transport of non-spherical particles in vitro. PCL is known to degrade only slowly, and these platelets were still stable after 2 days of incubation in artificial lysosomal media. Upon cell uptake, the platelets were transported through an endo/lysosomal pathway and were found to degrade completely in the lysosome at the end of the cell uptake cycle. We observed a morphological transformation of the lysosomes, which correlates with the stages of platelet degradation in the lysosome. Overall, we found an accelerated degradation of PCL, which was likely caused by mechanical forces inside the highly stretched endosomes.
Subject(s)
Polyesters , Polyethylene Glycols , Lysosomes , MacrophagesABSTRACT
Laboratory models of the tumor microenvironment require control of mechanical and biochemical properties to ensure accurate mimicry of patient disease. In contrast to pure natural or synthetic materials, hybrid approaches that pair recombinant protein fragments with synthetic scaffolding show many advantages. Here we demonstrate production of a recombinant bacterial collagen-like protein (CLP) for thiol-ene pairing to norbornene functionalized hyaluronic acid (NorHA). The resultant hydrogel material shows an adjustable modulus with evidence for strain-stiffening behavior that resembles natural tumor matrices. Cysteine terminated peptide binding motifs are incorporated to adjust the cell-adhesion points. The modular hybrid gel shows good biocompatibility and was demonstrated to control cell adhesion, proliferation, and the invasive properties of MCF7 and MD-MBA-231 breast adenocarcinoma cells. The ease in which multiple structural and bioactive components can be integrated provides a robust framework to form models of the tumor microenvironment for fundamental studies and drug development.
ABSTRACT
A critical challenge in the application of functional cellulose fibrils is to perform efficient surface modification without disrupting the original properties. Three-component Passerini reaction (Passerini 3-CR) is regarded as an effective functionalization approach which can be carried out under mild and fast reaction condition. In this study, we investigated the application of Passerini 3-CR for the synthesis of thermoresponsive cellulose fibrils by covalently tethering poly(N-isopropylacrylamide) in aqueous condition at ambient temperature. The three components, a TEMPO-oxidized cellulose nanofiber bearing carboxylic acid moieties (TOCN-COOH), a functionalized polymer with aldehyde group (pNIPAm-COH) and a cyclohexyl isocyanide, were reacted in one pot resulting in 36% of grafting efficiency within 30 min. The chemical coupling was evidenced by improved aqueous dispersibility, which was further confirmed by FT-IR, TGA, UV-vis, and turbidity study. It was observed that the grafting efficiency is strongly dependent on the chain length of the polymer. Furthermore, AFM and X-ray diffraction measurements affirmed the suitability of the proposed method for chemical modification of cellulose nanofibers without significantly compromising the original morphology and structural integrity.
ABSTRACT
Polymeric nanoparticles with long circulation time hold great promise for anti-cancer drug delivery. An enhanced circulation effect of rod-like micelles has been reported, yet efficient intracellular delivery, especially their interactions with cells during endocytosis, still remains inconsistent. Internalization of rod-like nanoparticles is significantly affected by a number of factors including aspect ratio, stiffness and surface chemistry of nanoparticles. Our previous research has shown that the length of rods affected their cellular uptake by breast cancer cells. Here, the influence of rod stiffness in cellular uptake was investigated to provide a comprehensive understanding of the interaction between rods and cells during endocytosis. Well-defined fructose-coated rod-like micelles of different lengths and stiffness were prepared successfully. The AFM results indicate that rods based on poly(1-O-MAFru)31-b-PMMA166 are significantly stiffer than those prepared from poly(1-O-MAFru)31-b-PBA158. The cellular uptake of these different rod-like micelles by breast cancer cells was investigated. In vitro studies via 2D and 3D cell culture models reveal that stiffer rods exhibit a higher cellular uptake and a deeper penetration into cells than the soft rod-like micelles. These results indicate that the internalization of rod-like micelles is significantly affected by their stiffness, though the length of rods also plays an important role. Our results yield a fundamental understanding of the stiffness effect of rod-like micelles on cellular uptake.