The extension of in vivo optical imaging for disease screening and image-guided surgical interventions requires brightly-emitting, tissue-specific materials that optically transmit through living tissue and can be imaged with portable systems that display data in real-time. Recent work suggests that a new window across the short wavelength infrared region can improve in vivo imaging sensitivity over near infrared light. Here we report on the first evidence of multispectral, real-time short wavelength infrared imaging offering anatomical resolution using brightly-emitting rare-earth nanomaterials and demonstrate their applicability toward disease-targeted imaging. Inorganic-protein nanocomposites of rare-earth nanomaterials with human serum albumin facilitated systemic biodistribution of the rare-earth nanomaterials resulting in the increased accumulation and retention in tumor tissue that was visualized by the localized enhancement of infrared signal intensity. Our findings lay the groundwork for a new generation of versatile, biomedical nanomaterials that can advance disease monitoring based on a pioneering infrared imaging technique.

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Van der Waals (dispersion) forces contribute to interactions of proteins with other molecules or with surfaces, but because of the structural complexity of protein molecules, the magnitude of these effects is usually estimated based on idealized models of the molecular geometry, e.g., spheres or spheroids. The calculations reported here seek to account for both the geometric irregularity of protein molecules and the material properties of the interacting media. Whereas the latter are found to fall in the generally accepted range, the molecular shape is shown to cause the magnitudes of the interactions to differ significantly from those calculated using idealized models, with important consequences. First, the roughness of the molecular surface leads to much lower average interaction energies for both protein-protein and protein-surface cases relative to calculations in which the protein molecule is approximated as a sphere. These results indicate that a form of steric stabilization may be an important effect in protein solutions. Underlying this behavior is appreciable orientational dependence, one reflection of which is that molecules of complementary shape are found to exhibit very strong attractive dispersion interactions. Although this has been widely discussed previously in the context of molecular recognition processes, the broader implications of these phenomena may also be important at larger molecular separations, e.g., in the dynamics of aggregation, precipitation, and crystal growth.

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Generation 5 poly(amidoamine) (PAMAM) dendrimers were modified by the addition of cyclic RGD targeting peptides and were evaluated for their ability to associate with siRNA and mediate siRNA delivery to U87 malignant glioma cells. PAMAM-RGD conjugates were able to complex with siRNA to form complexes of approximately 200 nm in size. Modest siRNA delivery was observed in U87 cells using either PAMAM or PAMAM-RGD conjugates. PAMAM-RGD conjugates prevented the adhesion of U87 cells to fibrinogen coated plates, in a manner that depends on the number of RGD ligands per dendrimer. The delivery of siRNA through threedimensional multicellular spheroids of U87 cells was enhanced using PAMAM-RGD conjugates compared to the native PAMAM dendrimers, presumably by interfering with integrin-ECM contacts present in a three-dimensional tumor model.

Background: The advancement of gene silencing via RNA interference is limited by the lack of effective short interfering RNA (siRNA) delivery vectors. Rational design of polymeric carriers has been complicated by the fact that most chemical modifications affect multiple aspects of the delivery process. In this work, the extent of primary amine acetylation of generation 5 poly(amidoamine) (PAMAM) dendrimers was studied as a modification for the delivery of siRNA to U87 malignant glioma cells.

Poor penetration of anticancer drugs into solid tumors significantly limits their efficacy. This phenomenon has long been observed for small-molecule chemotherapeutics, and it can be even more pronounced for nanoscale therapies. Nanoparticles have enormous potential for the treatment of cancer due to their wide applicability as drug delivery and imaging vehicles and their size-dependent accumulation into solid tumors by the enhanced permeability and retention (EPR) effect. Further, synthetic nanoparticles can be engineered to overcome barriers to drug delivery. Despite their promise for the treatment of cancer, relatively little work has been done to study and improve their ability to diffuse into solid tumors following passive accumulation in the tumor vasculature. In this review, we present the complex issues governing efficient penetration of nanoscale therapies into solid tumors. The current methods available to researchers to study nanoparticle penetration into malignant tumors are described, and the most recent works studying the penetration of nanoscale materials into solid tumors are summarized. We conclude with an overview of the important nanoparticle design parameters governing their tumor penetration, as well as by highlighting critical directions in this field.

Gene therapy is a new therapeutic modality with the potential of treating inherited and acquired diseases. Several viral and physicochemical vehicles have been used for the transfer of genes to mammalian cells, but recombinant retroviruses are used in the majority of gene therapy clinical trials today. In this communication, we review the major concerns associated with the large-scale production and processing of retroviral particles. While some of the current processes for manufacturing recombinant proteins will be applicable to recombinant retroviruses, the instability, sensitivity to inhibitors, complexity, and size of retroviral particles require that new technologies be designed and evaluated. Here, we examine those issues critical to the design of strategies for production, concentration, and purification as well as formulation and storage of recombinant retroviruses. Processes for large-scale manufacturing of recombinant retroviruses that can produce high gene transfer efficiencies will have significant impact on the clinical implementation of gene therapy.