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Ineffective drug delivery and poor prognosis are two major challenges in the treatment of pancreatic ductal adenocarcinoma (PDAC). While there is significant downregulation of tumor suppressor microRNA-34a (miR-34a), which targets many oncogenes related to proliferation, apoptosis and invasion, high expression level of Polo-like kinase 1 (PLK1) is closely associated with short survival rates of pancreatic cancer patients. Therefore, the objective is to co-deliver miR-34a mimic and small molecule PLK1 inhibitor volasertib (BI6727) using poly (ethylene glycol)-poly[aspartamidoethyl (p-boronobenzyl) diethyl ammonium bromide] (PEG-B-PAEBEA) This polymer can self-assemble into micelles of ~100 nm with 10 % drug loading of volasertib and form complex with miR-34a at the N/P ratio of 18 and higher. Combination treatment of volasertib and miR-34a displays synergistic effect and superior anti-proliferative activity along with an enhanced G2/M phase arrest and suppression of colony formation, leading to cell death due to potential c-myc targeting therapeutics. Orthotopic pancreatic tumor bearing NSG mice are scanned for fluorescence by IVIS after systemic administration of micelles encapsulating volasertib and miR-34a at doses of 5 mg/kg and 1 mg/kg, respectively. Cy5.5 concentration in plasma and major organs is determined by measuring fluorescence intensity. There is a significant reduction in tumor volume and negligible systemic toxicity as evident by hematological parameters and histological evaluation. In conclusion, PEG-B-PAEBEA micelles carrying volasertib and miR-34a mimic have great potential to improve drug delivery for pancreatic cancer treatment.
This article was published in the following journal.
Name: ACS applied materials & interfaces
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Particles consisting of aggregates of molecules held loosely together by secondary bonds. The surface of micelles are usually comprised of amphiphatic compounds that are oriented in a way that minimizes the energy of interaction between the micelle and its environment. Liquids that contain large numbers of suspended micelles are referred to as EMULSIONS.
Synthesized magnetic particles under 100 nanometers possessing many biomedical applications including DRUG DELIVERY SYSTEMS and CONTRAST AGENTS. The particles are usually coated with a variety of polymeric compounds.
Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
A 15 kD "joining" peptide that forms one of the linkages between monomers of IMMUNOGLOBULIN A or IMMUNOGLOBULIN M in the formation of polymeric immunoglobulins. There is one J chain per one IgA dimer or one IgM pentamer. It is also involved in binding the polymeric immunoglobulins to POLYMERIC IMMUNOGLOBULIN RECEPTOR which is necessary for their transcytosis to the lumen. It is distinguished from the IMMUNOGLOBULIN JOINING REGION which is part of the IMMUNOGLOBULIN VARIABLE REGION of the immunoglobulin light and heavy chains.
Specialized Fc receptors (RECEPTORS, FC) for polymeric immunoglobulins, which mediate transcytosis of polymeric IMMUNOGLOBULIN A and IMMUNOGLOBULIN M into external secretions. They are found on the surfaces of epithelial cells and hepatocytes. After binding to IMMUNOGLOBULIN A, the receptor-ligand complex undergoes endocytosis, transport by vesicle, and secretion into the lumen by exocytosis. Before release, the part of the receptor (SECRETORY COMPONENT) that is bound to IMMUNOGLOBULIN A is proteolytically cleaved from its transmembrane tail. (From Rosen et al., The Dictionary of Immunology, 1989)
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<!--LGfEGNT2Lhm-->Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. <!--LGfEGNT2Lhm-->Drug delivery technologies are <!--LGfEGNT2Lhm-->patent pr...