Surface engineering of a hydrogel nanoparticle (NP) with the tumor-targeting ligand, F3 peptide, enhances both the NP’s binding affinity for, and internalization by, nucleolin overexpressing tumor cells. Remarkably, the F3-functionalized NPs consistently exhibited significantly lower trafficking to the degradative lysosomes than the non-functionalized NPs, in the tumor cells, after internalization. This is attributed to the non-functionalized NPs, but not the F3-functionalized NPs, being co-internalized with Lysosome-associated Membrane Protein-1 (LAMP1) from the surface of the tumor cells. Furthermore, it is shown that the intracellular trafficking of the F3-functionalized NPs differs significantly from that of the single F3 peptides. This has important implications for designing effective, chemically-responsive, controlled-release and multifunctional nanodrugs for multi-drug-resistant cancers.
Here we present a new optical contrast agent, based on silver nanoplate clusters embedded inside a polymer nano matrix. Unlike nanosphere clusters, which have been well studied, nanoplate clusters have unique properties due to the different possible orientations of interaction between the individual plates, resulting in a significant broadening of the absorption spectra. These nanoclusters were immobilized inside a polymer cladding, so as to maintain their stability and optical properties under in vivo conditions. The polymer coated silver nanoplate clusters show a lower toxicity, compared to the uncoated nanoparticles. At high nanoparticle concentrations, cell death occurs mostly due to apoptosis. These nanoparticles were used for targeted fluorescence imaging in a rat glioma cell line by incorporating a fluorescent dye into the matrix, followed by conjugation of a tumor targeting F3 peptide. We further used these nanoparticles as photoacoustic contrast agents in vivo, to enhance the contrast of the vasculature structures in a rat ear model. We observed a contrast enhancement of over 90%, following nanoparticle injection. It is also shown that these NP’s can serve as efficient contrast agents, with specific targeting abilities, for broadband multimodal imaging, usable for diagnostic applications and extendable into use as therapeutic agents as well.
This study provides evidence that both EFV and NVP induce peripheral lymphocyte Deltapsim in HIV-1-infected patients on nonnucleoside reverse transcriptase inhibitor-based HAART, which in the case of NVP is sufficient to induce the apoptosis cascade.
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