It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles.biomimetic | deformability | drug carriers | long circulating | red blood cell mimic
The mechanochemistry of the bimolecular nucleophilic substitution of DMSO for substituted pyridines at a square-planar pincer Pd(II) center was investigated using single-molecule force spectroscopy (SMFS). The SMFS data are interpreted in terms of the Bell-Evans model, which gives thermal off-rates for two reactions that agree well with previous, stress-free measurements. The characteristic force dependency of the rupture rate, fbeta, is effectively constant for the two reactions examined (22 +/- 2 and 24 +/- 2 pN), and the system homology in the mechanical response is consistent with expected similarities in the reaction potential energy surfaces.
A family of hybrid polymer gels is described, in which covalent cross-links create a permanent, stiff scaffold onto which reversible metal-ligand coordinative cross-links are added. The reversible metal-ligand interactions are shown to bear mechanical stress within the hybrid gel, and relaxations in response to that applied stress are consistent with the stress-free kinetics of ligand exchange in systems that model the reversible cross-links. The stress-induced dissociation of a model metal-ligand complex is examined by a single-molecule force spectroscopy, and its mechanical response is compared with a previously studied complex. The mechanical response of the individual interactions is relevant to those found in the family of hybrid gels, and the modular platform is therefore suitable for the study of stress-induced molecular dissociations, and their subsequent repair, within a macroscopic material of fixed structure.
Self-assembled polymers whose main chains are defined by reversible DNA base pairing form bridges between the tip of an atomic force microscope and substrate. The forces associated with the rupture of these assemblies are independent of polymer bridge length, and they resemble those expected for the isolated associations defining the polymer bridges. The assembly is reversible and is inhibited by a competitive, nonpolymerizing oligonucleotide. Noncomplementary polymer brush layers do not bridge, and therefore, the forces result from specific molecular recognition events. The length distribution of the bridges differs greatly from that of the polymers in solution, and thus the bridging is responsive to the spatial constraints of the environment.
Responsive biomaterials play important roles in imaging, diagnostics, and therapeutics. Polymeric nanoparticles (NPs) containing hydrophobic and hydrophilic segments are one class of biomaterial utilized for these purposes. The incorporation of luminescent molecules into NPs adds optical imaging and sensing capability to these vectors. Here we report on the synthesis of dual-emissive, pegylated NPs with "stealth"-like properties, delivered intravenously (IV), for the study of tumor accumulation. The NPs were created by means of stereocomplexation using a methoxy-terminated polyethylene glycol and poly(D-lactide) (mPEG-PDLA) block copolymer combined with iodide-substituted difluoroboron dibenzoylmethane-poly(L-lactide) (BF 2 dbm(I)PLLA). Boron nanoparticles (BNPs) were fabricated in two different solvent compositions to study the effects on BNP size distribution. The physical and photoluminescent properties of the BNPs were studied in vitro over time to determine stability. Finally, preliminary in vivo results show that stereocomplexed BNPs injected IV are taken up by tumors, an important prerequisite to their use as hypoxia imaging agents in preclinical studies.
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