Combinatorial cetuximab targeted polymeric nanocomplexes reduce PRC1 level and abrogate growth of metastatic hepatocellular carcinoma in vivo with efficient radionuclide uptake.

Hepatocellular carcinoma (HCC) is the most aggressive form of cancer with poor drug responses. Developing an effective drug treatment remains a major unmet clinical need for HCC. We report a comprehensive study of combinatorial Cetuximab (Cet) targeted polymeric poly(D, L-lactide-co-glycolide)-b-poly(ethylene glycol) nanocomplexes delivery of Combretastatin A4 (CA4) and 2-Methoxyestradiol (2ME) (Cet-PLGA-b-PEG-CA4 NP + Cet-PLGA-b-PEG-2ME NP) against metastatic HCC in SCID mice.

Distinct stratification of normal liver, hepatocellular carcinoma (HCC), and anticancer nanomedicine-treated- tumor tissues by Raman fingerprinting for HCC therapeutic monitoring.

Hepatocellular carcinomas (HCCs) are highly vascularized neoplasms with poor prognosis. Nanomedicine possesses great potential to deliver therapeutics and diagnostics. The new aspect of this study is that we have monitored, for the first time, the Raman responses to microtubule targeted vascular disrupting agents (MTVDA), MTVDA encapsulated non-targeted, and targeted cetuximab polymeric nanocomplexes delivery of combinatorial therapeutics in HCC tumor tissues of mice.

Antihepatoma activity of multifunctional polymeric nanoparticles via inhibition of microtubules and tyrosine kinases.

Synthesis of poly-L-lactic acid nanoparticles comprising of microtubule-inhibitor docetaxel and tyrosine kinase inhibitor sorafenib (PLDS NPs) for hepatoma treatment. PLDS NPs were prepared by the emulsion solvent evaporation method and the anticancer activity was evaluated in Huh7 hepatoma cells. Real-time imaging of quantum dots incorporating poly-L-lactic acid nanoparticles showed a rapid internalization of the nanoparticles in Huh7 cells.

Enhanced EPR directed and Imaging guided Photothermal Therapy using Vitamin E Modified Toco-Photoxil.

Herein we report synthesis, characterization and preclinical applications of a novel hybrid nanomaterial Toco-Photoxil developed using vitamin E modified gold coated poly (lactic-co-glycolic acid) nanoshells incorporating Pgp inhibitor d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a highly inert and disintegrable photothermal therapy (PTT) agent. Toco-Photoxil is highly biocompatible, physiologically stable PTT material with an average diameter of 130 nm that shows good passive accumulation (2.3% ID) in solid tumors when delivered systemically.

Intracellular interactions of electrostatically mediated layer-by-layer assembled polyelectrolytes based sorafenib nanoparticles in oral cancer cells.

In this paper, we report the preparation of LbL-nanoSraf (100-300nm) comprising of layer-by-layer (LbL) assembled polyelectrolytes dextran-sulfate/poly-l-arginine, with a multikinase inhibitor sorafenib (Sraf) encapsulated calcium carbonate (CaCO3) nanoparticles for oral cancer therapy in vitro. The zeta potential of LbL-nanoSraf exhibited a negative charge of the polyanionic dextran sulfate, which alternated with a positive charge of polycationic poly-l-arginine indicating a successful LbL assembly of the two polyelectrolyte bilayers on the CaCO3 nanoparticles. The LbL-nanoSraf exhibited an encapsulation efficiency of 61±4%.

Microtubule targeted therapeutics loaded polymeric assembled nanospheres for potentiation of antineoplastic activity.

Polymeric nanoassemblies represent an attractive strategy for efficient cellular internalization of microtubule targeted anticancer drugs. Using dynamic light scattering, zeta potential, transmission electron microscopy and scanning electron microscopy, the physical properties and surface morphology of microtubule-binding PEGylated PLGA assembled nanospheres (100-200 nm) were analyzed. The present approach leads to strong internalization as observed by confocal laser scanning microscopy and transmission electron microscopy in hepatocarcinoma cells.

A Chimeric Cetuximab-Functionalized Corona as a Potent Delivery System for Microtubule-Destabilizing Nanocomplexes to Hepatocellular Carcinoma Cells: A Focus on EGFR and Tubulin Intracellular Dynamics.

In this study, we have developed microtubule destabilizing agents combretastatin A4 (CA4) or 2-methoxyestradiol (2ME) encapsulated poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) nanocomplexes for targeted delivery to human hepatocellular carcinoma (HCC) cells. An epidermal growth factor receptor (EGFR) is known to be overexpressed in HCC cells. Therefore, the targeting moiety cetuximab (Cet), an anti-EGFR chimeric monoclonal antibody, is functionalized on the surface of these diblock copolymeric coronas.

Embelin - a drug of antiquity: shifting the paradigm towards modern medicine.

Introduction: Embelia ribes or Embelia tsjeriam-cottam, more commonly known as vidanga, is a type of ayurvedic medicine that has been used to treat various diseases for a number of years. Bright orange embelin -rich fruits have been well established as ethnomedicinals, for a number of years with their pharmacological actions attributed to their hydroxybenzoquinone active constituent. Embelin has become known specifically for its antihelminthic and contraceptive use.

Composite alginate microspheres as the next-generation egg-box carriers for biomacromolecules delivery.

Introduction: Alginate microspheres are versatile tools for the delivery of a wide range of therapeutic biomacromolecules. This naturally occurring biopolymer has many unique properties making it an ideal candidate for tailoring with different composites of polymers leading to the formation of strong complexes for a broad range of applications.

Areas Covered: This article overviews various types of composite alginate microspheres, methods of preparation, new technologies available, physico-chemical characteristics, controlled release profiles, applications and the future directions of composite alginate microsphere delivery system for biomacromolecules.

Chemopreventive and hepatoprotective effects of embelin on N-nitrosodiethylamine and carbon tetrachloride induced preneoplasia and toxicity in rat liver.

Embelin, an active constituent isolated from the fruits of Embelia tsjeriam cottam was investigated for its chemopreventive and hepatoprotective effects against N-nitrosodiethylamine (NDEA) induced liver preneoplasia or carbon tetrachloride (CCl4) induced liver damage. Rats received NDEA, 1 ppm/g b.w.

Sida rhombifolia ssp. retusa seed extract inhibits DEN induced murine hepatic preneoplasia and carbon tetrachloride hepatotoxicity.

Sida rhombifolia ssp. retusa is a well established drug in the Ayurvedic system of medicine used for antirheumatism and antiasthmatism. Inhibitory effects of S.