Gold

Surgery, radiation and chemotherapy remain the mainstay of current cancer therapy. However, treatment failure persists due to the inability to achieve complete local control of the tumor and curtail metastatic spread. Vascular disrupting agents (VDAs) are a class of promising systemic agents that are known to synergistically enhance radiation, chemotherapy or thermal treatments of solid tumors. Unfortunately, there is still an unmet need for VDAs with more favorable safety profiles and fewer side effects. Recent work has demonstrated that conjugating VDAs to other molecules (polyethylene glycol, CNGRCG peptide) or nanoparticles (liposomes, gold) can reduce toxicity of one prominent VDA (tumor necrosis factor alpha, TNF-α). In this report, we show the potential of a gold conjugated TNF-α nanoparticle (NP-TNF) to improve multimodal cancer therapies with VDAs. In a dorsal skin fold and hindlimb murine xenograft model of prostate cancer, we found that NP-TNF disrupts endothelial barrier function and induces a significant increase in vascular permeability within the first 1−2 h followed by a dramatic 80% drop in perfusion 2−6 h after systemic administration. We also demonstrate that the tumor response to the nanoparticle can be verified using dynamic contrast-enhanced magnetic resonance imaging (MRI), a technique in clinical use. Additionally, multimodal treatment with thermal therapies at the perfusion nadir in the suband supraphysiological temperature regimes increases tumor volumetric destruction by over 60% and leads to significant tumor growth delays compared to thermal therapy alone. Lastly, NP-TNF was found to enhance thermal therapy in the absence of neutrophil recruitment, suggesting that immune/inflammatory regulation is not central to its power as part of a multimodal approach. Our data demonstrate the potential of nanoparticle-conjugated VDAs to significantly improve cancer therapy by preconditioning tumor vasculature to a secondary insult in a targeted manner. We anticipate our work to direct investigations into more potent tumor vasculature specific combinations of VDAs and nanoparticles with the goal of transitioning optimal regimens into clinical trials.

A nanoscale range of surface feature curvatures where lipid membranes lose integrity and form pores has been found experimentally. The pores were experimentally observed in the L-r-dimyristoyl phosphatidylcholine membrane around 1.2-22 nm polar nanoparticles deposited on mica surface. Lipid bilayer envelops or closely follows surface features with the curvatures outside of that region. This finding provides essential information for the understanding of nanoparticle-lipid membrane interaction, cytotoxicity, preparation of biomolecular templates and supported lipid membranes on rough and patterned surfaces.

In this work for first time a lateral flow immunosensor device (LFID) for Cd 2 þ determination in drinking and tap waters using the Cd-EDTA-BSA-AuNP conjugate as signal producer tool is introduced. The principle of working is based on competitive reaction between the Cd-EDTA-BSA-AuNP conjugate deposited on the conjugation pad strip and the Cd-EDTA complex formed in the analysis sample for the same binding sites of the 2A81G5 monoclonal antibody, specific to Cd-EDTA but not Cd 2 þ free, which is immobilized onto the test line. The device has a large response range within 0.4-2000 ppb, being the linear response between 0.4 and 10 ppb. The quantification and detection limits of 0.4 and 0.1 ppb, respectively, represent the lowest ones reported so far for paper based metal sensors. The obtained detection limit is 50 times lower than the maximum contamination level required for drinking water.

Gold nanoparticles of two different sizes stabilized by a 15-mer peptide ligand specifically designed for this purpose have been prepared in aqueous solution and characterized by UV-vis spectroscopy and TEM. The presence of the ligand and its binding mode to the particles via its four cystein thiols is evidenced by FTIR and NMR spectroscopy. Biotinylation of the particles via binding to a freely accessible lysine residue is demonstrated.