Protein Based Ligands For Tumor Targeting

Cancer is a disease caused by an uncontrolled division of abnormal cells. The DNA sequence in cells can be changed as a result of copying errors during replication. If these changes whatever their cause are left uncorrected, both growing and non-growing somatic cells might gain many mutations that they could no longer function. The relevance of DNA damage and repair to the generation of cancer was obvious when it was recognized that everything that causes cancer also cause a change in the DNA sequence. Tumor suppressor genes are protective genes and normally they limit cell growth by monitoring the speed of cell division, repair mismatched DNA and control when a cell dies. When a tumor suppressor gene is mutated cells grow

Nanocarriers (NCs) have emerged as a favored drug delivery approach towards improving the anticancer benefits of several bioactives for cancer therapy with recent reports showing the application of NC systems in clinical settings [18]. The NCs with size < 100 nm have been associated with enhanced permeation and retention effect (EPR) due to the presence of leaky vasculature in the tumor tissues which contributes to its enhanced efficacy. Also recently, NCs have shown to be effective in the treatment of malignant mesothelioma [19]. A recent study by Kanai et al. showed that the NC albumin-bound paclitaxel and carboplatin (nabPC) repetitively achieved tumor regression in malignant mesothelioma

Reception is the target cell's detection of the signal via binding of a signaling molecule, or ligand. Ligand is a complex biomolecule, usually a protein. Receptor proteins span the cell’s plasma membrane and provide specific sites for water-soluble signaling molecules to bind to Receptors are found in two places; Intracellular proteins are found inside the plasma membrane in the cytoplasm or nucleus.Cell-surface proteins are embedded in the plasma membrane These transmembrane receptors are able to transmit information from outside the cell to the inside because they can transform, when a specific ligand binds to it.

RECIST 1.0 was introduced in 2000 as a standardised method to evaluate response to treatment with chemotherapeutic agents(Patrick Therasse, Richard S. Kaplan et al. 2000). This has been further updated in 2009 (Eisenhauer, Therasse et al. 2009). Treatment response defined by RECIST depends solely on size change of the target tumours. It looks at the change in size of the sum of uni-dimensional measurements of tumour target lesions performed with a specific imaging modality.

In this study,the success of siRNA-based gene theraphy in vitro is doubled by in-vivo studies.However,some researchers performing siRNA delivery in vivo in mice introduce naked siRNA by high-pressure tail injections [1]. High-pressure injections, however, would be fatal for humans and are not a realistic in vivo method of naked siRNA delivery [2].I would like to know if this gold nanoparticle conjugates might be same affect on human.Because of that,I suggest that gold particles should be tracked via MRI imaging after systemic injection to evaluate targeting or manipulated to target

In vitro: Previous study found that AG-370 inhibited PDGF receptor autophosphorylation and the tyrosine phosphorylation of intracellular protein substrates that coprecipitated with the PDGF receptor in digitonin-permeabilized

Tumor angiogenesis refers to an attribute of tumor cells residing with the capacity to elicit continuously the growth of new capillary endothelium. Tumor angiogenesis occurs by recruitment of endothelial cell precursor or by sprouting of existing capillaries as in physiologic angiogenesis. Angiogenesis (the formation of new blood vessels) is implicated in the pathogenesis of many chronic diseases including cancer. Angiogenesis in the tumor mass permits growth and invasiveness of the cancer cells as it is believed to be essential for the delivery of essential nutrients and oxygen to the tumor microenvironment. Clustered evidence suggests that angiogenesis is a critical event in the progression of solid tumors because tumor growth beyond 2 to

The efficient delivery of drugs and energy to tumors faces several difficulties and obstacles that need to be overcome for effective cancer treatment. Nanoparticles administrated through intravenous injections accumulate at a tumor site due to the enhanced permeability and retention (EPR) effect, but only a small quantity of the injected particles can actually “reach the tumor” (Su et al, 2016). The majority of the nanoparticles interact with “cancer cells at the periphery of a tumor” which presents a “physiological barrier” that prevents most of the injected particles from reaching the tumor (Su et al, 2016). In addition to this barrier, there is also another significant obstacle, “cancer-associated fibroblasts”, which can also

The estimated doses of 17-AAG and PTX contained in this amount of protein are approximately 200 μg/kg and 280 μg/kg, respectively. Administrations will continue until complete tumor regression is confirmed by a caliper measurement. In the preliminary studies, we infused the H-GBD or the H-GBD/17-AAG once a week into the SK-BR-3 tumor mice or the MDA-MB-231 tumor mice through the tail vein at a dose of 200 μg/kg 17-AAG. The H-GBD was mixed with 17-AAG at a 1:1 molar ratio and the amount of the H-GBD infused was equivalent to the amount of the H-GBD used to formulate the H-GBD/17-AAG. In the SK-BR-3 tumor model, the H-GBD/17-AAG significantly reduced the volume of the tumor, while the H-GBD slightly reduced the tumor volume (Fig. 8). In the MDA-MB-231 HER2-negative tumor model, however, neither formulation demonstrated any anti-cancer efficacy. These results confirm that the H-GBD/17-AAG increases the anti-cancer efficacy of the parent agent and/or that of the H-GBD as an anti-HER2

Contrast agents are used in many Magnetic resonance imaging procedures to help in identifying the interior anatomy by improving the quality of images. Traditionally, contrast agents can be divided into two groups according to their effect on relaxation times. T1 longitudinal relaxation time can be enhanced by Mn+2 chelates, while T2 transverse relaxation time is can be enhanced by iron oxide nanoparticles. New contrast agents have been developed during the last decades showed some benefits in the field of molecular imaging called smart contrast agents. These agents allows to trigger some active molecules within a cellular environment or a physiological response in a tissue. Any smart agent in order to be used in vivo must show a

We present experimental and theoretical results from a study of adhesion and the entry of magnetite nanoparticles (MNP) into MDA-MB-231 breast cancer cells. The adhesion between Luteinizing Hormone Releasing Hormone (LHRH) and breast cancer cells is studied using an atomic force microscopy (AFM) technique. The adhesion force between LHRH coated AFM tips and MDA-MB-231 breast cancer cells is shown to be about twice that between bare/uncoated AFM tips and breast cancer cells, while the adhesion force between LHRH-MNP coated AFM tips is also approximately twice as much as that between MNP coated AFM tips and breast cancer cells. The increased adhesion of the LHRH-coated tips suggests that LHRH can be used as a molecular recognition unit for

The encapsulation and site-directed mechanisms can also be translated and utilized in bioimaging – the field of study concerned with developing imaging techniques and devices that are used to obtain anatomical images and provide tissue analysis. Medical professionals are always looking for answers as to what is going on inside one’s body. Nanoparticles can serve as excellent scaffolds in this area of research because they have such a high surface area- to- volume ratio [9]. Ferritin, in particular, has been modified in different ways, mainly using the techniques described earlier, to further advancements in this field.

Our biological affinity-driven antibody-drug complex makes targeted simultaneous delivery of multiple anti-cancer agents possible, something that is currently impossible to do via antibody-drug conjugate (ADC) technologies. More specifically, our multi-functional recombinant fusion protein comprises a single-chain fragment variable (scFv) antibody and anti-cancer agent-binding domains (ABDs) that make it a feasible platform for targeted combination chemotherapy. The scFv antibody serves as a targeting moiety, while the ABDs capture their ligand anti-cancer agents through biological affinity. In other words, the affinity binding enables homogenous drug incorporation to an scFv antibody only because each ABD captures a single molecule of its

The structural analysis of nanodisc bound A1-40 ¬suggests the formation of intermediate conformation with typical sheet structures driven by the PMA. We next characterized the toxicity of these A1-40 intermediates in human neuroblastoma (SH-SY5Y) cells. Results showed substantial cytotoxic behavior of PMA in solution with a cell viability loss of ≈ 40 % at 2.5 M. The A1-40 monomer and fibers (2.5 M) incubated with equimolar PMA also showed a nearly equivalent cell cytotoxicity as that of the free PMA. In contrast, the PMA bound nanodiscs (Fig 5b) such as DMPC/GM1 (4:1) and DMPC (100 %) showed a relatively low cytotoxicity (< ≈ 10 %). On the other hand, the anionic

Colorectal cancer is one of the fatal diseases of this era with quite higher incidence rate. Due to a high fatality rate, health organizations and researchers are continuously looking for new and better management options. In this strive, nanotechnology served as a major and novel treatment methodology with betterment and more optimum outcomes. Work is carried out with respect to colo-rectal malignancies where nano-particles are either used as diagnostic tools or they serve as treatment tools for targeted drug delivery to the tumor cells. This all leads to more specific and sensitive drug delivery to site of action thus minimizing the dose associated and non-specific drug delivery side-effects. The following review article will address such efforts and their impact to reduce disease burden, thus improving future prospects of the disease.