Label-Free Determination of the Number of Biomolecules Attached to Cells by Measurement of the Cell's Electrophoretic Mobility in a Microchannel

We developed a label-free method for a determination of the number of biomolecules attached to individual cells by measuring the electrophoretic mobility of the cells in a microchannel. The surface of a biological cell, which is dispersed in aqueous solution, is normally electrically charged and the charge quantity at the cell's surface is slightly changed once antibody molecules are attached to the cell, based on which we detect the attachment of antibody molecules to the surface of individual red blood cells by electrophoretic mobility measurement. We also analyzed the number of antibody molecules attached to the cell's surface using a flow cytometer. We found that there is a clear correlation between the number of antibody molecules attached to the individual cells and the electophoretic mobility of the cells. The present technique may well be utilized not only in the field of cell biology but also in the medical and pharmaceutical industries

Advanced Microscopic Evaluation of Parallel Type I and Type II Cell deaths Induced by Multi-functionalized Gold Nanocages in Breast Cancer

Despite aggressive surgical resections and combinatorial chemoradiations, certain highly malignant populations of tumor cells resurrect and metastasize. Mixed-grade cancer cells fail to respond to standard-of-care therapies by developing intrinsic chemoresistance and subsequently result in tumor relapse. Macroautophagy is a membrane trafficking process that underlies drug resistance and tumorigenesis in most breast cancers. Manipulating cellular homeostasis by a combinatorial nanotherapeutic model, one can evaluate the crosstalk between type I and type II cell death and decipher the fate of cancer therapy. Here, we present a multi-strategic approach in cancer targeting to mitigate the autophagic flux with subcellular toxicity via lysosome permeation, accompanied by mitochondrial perturbation and apoptosis. In this way, a nanoformulation is developed with a unique blend of a lysosomotropic agent, an immunomodulating sulfated-polysaccharide, an adjuvant chemotherapeutic agent, and a monoclonal antibody as a broad-spectrum complex for combinatorial nanotherapy of all breast cancers. To the best of our knowledge, this manuscript illustrates for the first time the applications of advanced microscopic techniques such as electron tomography, three-dimensional rendering and segmentation of subcellular interactions, and fate of the multifunctional therapeutic gold nanocages specifically targeted toward breast cancer cells

Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation for Cancer Therapy

Drugs targeting heat shock protein 90 (Hsp90) have been extensively explored for their anticancer potential in advanced clinical trials. Nanoformulations have been an important drug delivery platform for the anticancer molecules like Hsp90 inhibitors. It has been reported that bovine serum albumin (BSA) nanoparticles (NPs) serve as carriers for anticancer drugs, which have been extensively explored for their therapeutic efficacy against cancers. Luminespib (also known as NVP-AUY922) is a new generation Hsp90 inhibitor that was introduced recently. It is one of the most studied Hsp90 inhibitors for a variety of cancers in Phase I and II clinical trials and is similar to its predecessors such as the ansamycin class of molecules. To our knowledge, nanoformulations for luminespib remain unexplored for their anticancer potential. In the present study, we developed aqueous dispensable BSA NPs for controlled delivery of luminespib. The luminespib-loaded BSA NPs were characterized by SEM, TEM, FTIR, XPS, UV-visible spectroscopy and fluorescence spectroscopy. The results suggest that luminespib interacts by non-covalent reversible interactions with BSA to form drug-loaded BSA NPs (DNPs). Our in vitro evaluations suggest that DNP-based aqueous nanoformulations can be used in both pancreatic (MIA PaCa-2) and breast (MCF-7) cancer therapy

Template-Assisted Synthesis and Characterization of Passivated Nickel Nanoparticles

Potential applications of nickel nanoparticles demand the synthesis of self-protected nickel nanoparticles by different synthesis techniques. A novel and simple technique for the synthesis of self-protected nickel nanoparticles is realized by the inter-matrix synthesis of nickel nanoparticles by cation exchange reduction in two types of resins. Two different polymer templates namely strongly acidic cation exchange resins and weakly acidic cation exchange resins provided with cation exchange sites which can anchor metal cations by the ion exchange process are used. The nickel ions which are held at the cation exchange sites by ion fixation can be subsequently reduced to metal nanoparticles by using sodium borohydride as the reducing agent. The composites are cycled repeating the loading reduction cycle involved in the synthesis procedure. X-Ray Diffraction, Scanning Electron Microscopy, Transmission Electron microscopy, Energy Dispersive Spectrum, and Inductively Coupled Plasma Analysis are effectively utilized to investigate the different structural characteristics of the nanocomposites. The hysteresis loop parameters namely saturation magnetization and coercivity are measured using Vibrating Sample Magnetometer. The thermomagnetization study is also conducted to evaluate the Curie temperature values of the composites. The effect of cycling on the structural and magnetic characteristics of the two composites are dealt in detail. A comparison between the different characteristics of the two nanocomposites is also provided