Theranostic immunoliposomes for osteoarthritis.

Although there have been substantial advancements in the treatment of inflammatory arthritis, treatments for osteoarthritis (OA) have lagged and currently are primarily palliative until joints become totally dysfunctional and prosthetic replacement is needed. One obstacle for developing a preventive therapy for OA is the lack of good tools for efficiently diagnosing the disease and monitoring its progression during the early stages when the effect of therapeutic drugs or biologics is most likely to be effective. We have developed near infrared immunoliposomes conjugated with type II collagen antibody for diagnosis and treatment of early OA. These immunoliposomes bind to damaged but not normal cartilage. Utilizing these reagents, we can quantitate exposure of type II collagen during cartilage degradation in individual joints in vivo in a guinea pig. Immunoliposomes could be used to determine the effectiveness of therapeutic interventions in small animals as well as vehicles for localized drug delivery to OA chondrocytes. FROM THE CLINICAL EDITOR: This team of authors have developed near infrared immunoliposomes conjugated with type II collagen antibody for diagnosis and treatment of early OA, with promising results demonstrated in a guinea pig model.

Gated and near-surface diffusion of charged fullerenes in nanochannels.

Nanoparticles and their derivatives have engendered significant recent interest. Despite considerable advances in nanofluidic physics, control over nanoparticle diffusive transport, requisite for a host of innovative applications, has yet to be demonstrated. In this study, we performed diffusion experiments for negatively and positively charged fullerene derivatives (dendritic fullerene-1, DF-1, and amino fullerene, AC60) in 5.7 and 13 nm silicon nanochannels in solutions with different ionic strengths. With DF-1, we demonstrated a gated diffusion whereby precise and reproducible control of the dynamics of the release profile was achieved by tuning the gradient of the ionic strength within the nanochannels. With AC60, we observed a near-surface diffusive transport that produced release rates that were independent of the size of the nanochannels within the range of our experiments. Finally, through theoretical analysis we were able to elucidate the relative importance of physical nanoconfinement, electrostatic interactions, and ionic strength heterogeneity with respect to these gated and near-surface diffusive transport phenomena. These results are significant for multiple applications, including the controlled administration of targeted nanovectors for therapeutics.

Controlled loading of building blocks into temporary self-assembled scaffolds for directed assembly of organic nanostructures.

Using temporary self-assembled scaffolds to preorganize building blocks is a potentially powerful method for the synthesis of organic nanostructures with programmed shapes. We examined the underlying phenomena governing the loading of hydrophobic monomers into lipid bilayer interior and demonstrated successful control of the amount and ratio of loaded monomers. When excess styrene derivatives or acrylates were added to the aqueous solution of unilamellar liposomes made from saturated phospholipids, most loading occurs within the first few hours. Dynamic light scattering and transmission electron microscopy revealed no evidence of aggregation caused by monomers. Bilayers appeared to have a certain capacity for accommodating monomers. The total volume of loaded monomers is independent of monomer structure. X-ray scattering showed the increase in bilayer thickness consistent with loading monomers into bilayer interior. Loading kinetics is inversely proportional to the hydrophobicity and size of monomers. Loading and extraction kinetic data suggest that crossing the polar heads region is the rate limiting step. Consideration of loading kinetics and multiple equilibria are important for achieving reproducible monomer loading. The total amount of monomers loaded into the bilayer can be controlled by the loading time or length of hydrophobic lipid tails. The ratio of loaded monomers can be varied by changing the ratio of monomers used for loading or by the time-controlled replacement of a preloaded monomer. Understanding and controlling the loading of monomers into bilayers contributes to the directed assembly of organic nanostructures.

Increasing permeability of phospholipid bilayer membranes to alanine with synthetic alpha-aminophosphonate carriers.

A series of aminophosphonates was synthesized, and their ability to carry alanine, a model hydrophilic molecule, across phospholipid bilayer membranes was evaluated. Aminophosphonates facilitate the membrane transport at moderate rates, which make them a suitable platform for the design of carriers for continuous drug release devices.