Temporal response of an injectable calcium phosphate material in a critical size defect.

Background: Calcium phosphate-based bone graft substitutes are used to facilitate healing in bony defects caused by trauma or created during surgery. Here, we present an injectable calcium phosphate-based bone void filler that has been purposefully formulated with hyaluronic acid to offer a longer working time for ease of injection into bony defects that are difficult to access during minimally invasive surgery.

Methods: The bone substitute material deliverability and physical properties were characterized, and in vivo response was evaluated in a critical size distal femur defect in skeletally mature rabbits to 26 weeks.

Targeting CD4 Cells with Anti-CD4 Conjugated Mertansine-Loaded Nanogels.

CD4 T lymphocytes play an important role in controlling many malignancies. The modulation of CD4 T cells through immunomodulatory or cytotoxic drugs could change the course of disease progression for disorders such as autoimmunity, immunodeficiency, and cancer. Here, we demonstrate that anti-CD4 conjugated polymeric nanogels can deliver a small molecule cargo to primary CD4 T cells and a CD4 T cell lymphoma.

Improved mass spectrometric detection of acidic peptides by variations in the functional group pK values of reverse micelle extraction agents.

Polymeric reverse micelles can be used to selectively extract peptides from complex mixtures via a two-phase extraction approach. In previous work, we have shown that the charge polarity of the hydrophilic functional group that is in the interior of the reverse micelle dictates the extraction selectivity. To investigate how the extraction is influenced by the inherent pK of the functional group, we designed and tested a series of polymeric reverse micelles with variations in the hydrophilic functional group.

Biodistribution Analysis of NIR-Labeled Nanogels Using in Vivo FMT Imaging in Triple Negative Human Mammary Carcinoma Models.

The purpose of this study is to evaluate the biodistribution properties of random-copolymer-based core-cross-linked nanogels of various sizes and surface poly(ethylene glycol) composition. Systematic variations of near-IR labeled nanogels, comprising varying particle sizes (28-135 nm), PEG corona quantity (0-50 mol %), and PEG length (PEG M 1000, 2000, and 5000), were prepared and injected in mice that had been subcutaneously implanted with MDA-MB-231-luc-D3H2LN human mammary carcinoma. In vivo biodistribution was obtained using fluorescence molecular tomography imaging at 0, 6, 24, 48, and 72 h postinjection.

Matrix Metalloproteinase-9-Responsive Nanogels for Proximal Surface Conversion and Activated Cellular Uptake.

Here, we have exploited the heightened extracellular concentration of matrix metalloproteinase-9 (MMP-9) to induce surface-conversional properties of nanogels with the aim of tumor-specific enhanced cellular uptake. A modular polymeric nanogel platform was designed and synthesized for facile formulation and validation of MMP-9-mediated dePEGylation and generation of polyamine-type surface characteristics through peptide N-termini. Nanogels containing MMP-9-cleavable motifs and different poly(ethylene glycol) corona lengths (350 and 750 g/mol) were prepared, and enzymatic surface conversional properties were validated by MALDI characterization of cleaved byproducts, fluorescamine assay amine quantification, and zeta potential.

Field Guide to Challenges and Opportunities in Antibody-Drug Conjugates for Chemists.

Antibody-drug conjugates have attracted a great amount of attention as a therapeutic strategy for diseases where targeting specific tissues and cells are critical components, such as in cancer therapy. Although promising, the number of approved ADC drugs is relatively limited. This emanates from the challenges associated with generating the conjugates and the complexities associated with the stability requirements for these conjugates during circulation and after reaching the target.

Multi-stimuli responsive macromolecules and their assemblies.

In this review, we outline examples that illustrate the design criteria for achieving macromolecular assemblies that incorporate a combination of two or more chemical, physical or biological stimuli-responsive components. Progress in both fundamental investigation into the phase transformations of these polymers in response to multiple stimuli and their utilization in a variety of practical applications are highlighted. Using these examples, we aim to explain the origin of employed mechanisms of stimuli responsiveness which may serve as a guideline to inspire future design of multi-stimuli responsive materials.