curcumin and 1-2-distearoylphosphatidylethanolamine

To remedy the problems resulting from the usage of anti-cancer drugs in cancer chemotherapy, such as deficient drug concentration in tumour cells, low water-solubility and non-specific distribution of antitumour drugs, a kind of reduction-sensitive polymer prodrug of curcumin (Cur) containing in the nano-echinus was synthesized and designed. The nano-echinus-like nanomedicine presented synergistic effect with glycyrrhetic acid (GA) and oligomeric hyaluronic (HA) for targeting and combating HepG2 human liver cancer cell. Firstly, a kind of small molecular prodrug of Cur, dithiodipropionic acid-Cur (-SS-Cur), was chemically conjugated onto the side chain of the conjugated glycyrrhetic acid- oligomeric hyaluronic (GA-HA) to generate an amphiphilic polymeric prodrug of Cur, GA-HA-SS-Cur. The obtained GA-HA-SS-Cur prodrug and subsidiary material mPEG-DSPE could self-assemble into a sea urchin-like micelles in aqueous media and release Cur rapidly in response to glutathion (GSH). Then, Cur was loaded into the nano-echinus with a particle size of (118.1 ± 0.2 nm) and drug-loading efficiency of (8.03 ± 2.1%). The structure of GA-HA-SS-Cur was characterized by

Topics: Animals; Biological Transport; Biomimetic Materials; Chemistry Techniques, Synthetic; Curcumin; Drug Carriers; Drug Liberation; Hep G2 Cells; Humans; Mice; Mice, Nude; Micelles; Nanomedicine; Oxidation-Reduction; Particle Size; Phosphatidylethanolamines; Sea Urchins

Natural compounds have been studied as a source of countless bioactive compounds with diverse activities. Among them, many dietary phytochemicals have been thoroughly studied for their cytotoxic or apoptotic effects in several cellular models in order to explain their anticancer capacity. Curcumin and resveratrol are two natural compounds with a large body of evidence showing their cytotoxic activity against a wide variety of cancer cells; however, their poor absorption, bioavailability, and low selectivity have limited their clinical use. With the aim of improving bioavailability and selectivity, the antiproliferative effects of free-, liposomed-, and immunoliposomed-curcumin and/or resveratrol formulations have been compared in two human breast cancer cell lines with different HER2 expression levels. The results demonstrate that when HER2-targeted immunoliposomes are coupled to trastuzumab there is a dramatic increase in the antiproliferative effects of curcumin and resveratrol in HER2 positive human breast cancer cells in comparison to regular liposomed or free forms, indicating an increase of its therapeutic effect. The enhancement of the cytotoxic effects was also correlated to the uptake of curcumin at intracellular level, as shown by using ImageStream technique. The striking efficacy of the immunoliposomed formulation containing both resveratrol and curcumin suggests a multitargeted mechanism of action that deserves further study. These findings show the potential of HER2-targeted nanovesicles to develop new drug delivery systems for cancer therapy based on these compounds and justify further preclinical trials.

Topics: Antibodies, Monoclonal, Humanized; Anticarcinogenic Agents; Antineoplastic Agents; Biological Availability; Biological Products; Breast Neoplasms; Carcinoma, Ductal, Breast; Cell Division; Cell Line, Tumor; Cholesterol; Chromatography, High Pressure Liquid; Curcumin; Drug Compounding; Drug Screening Assays, Antitumor; Female; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Humans; Immunoconjugates; Liposomes; Neoplasm Proteins; Particle Size; Phosphatidylcholines; Phosphatidylethanolamines; Receptor, ErbB-2; Resveratrol; Stilbenes; Trastuzumab