title: Curcumin-encapsulating Nanogels as an Effective Anticancer Formulation for Intracellular Uptake.
abstract: Nanoscale drug delivery systems represent an attractive strategy to improve both the efficacy and safety of anticancer drugs. In this work, we describe nanoformulation of curcumin, a most potent natural anticancer compound capable of killing cancer cells while sparing the normal tissues. Since curcumin is a natural hydrophobic polyphenol, it has a low aqueous solubility and bioavailability, which are challenging to its therapeutic efficacy. We developed and evaluated a novel colloidal nanogel carrier for encapsulation of curcumin to increase its solubility and cytotoxicity. Amphiphilic Poloxamer-cationic network in the nanogel NG127 was designed to efficiently encapsulate curcumin. Homogenous drug complexes were obtained with 20-25% content of curcumin and the particle size of ca. 150 nm. Using ImageStream multispectral imaging flow cytometry, we demonstrated that the curcumin-nanogel formulation (C-NG) was readily internalized into MDA-231 breast cancer cells. A real-time cell growth electronic sensing assay was used to measure proliferation responses of various breast cancer cells to C-NG treatments. Our results indicated that the C-NG formulation was 70-85% more effective in inhibiting growth, at concentrations lower than IC50of free curcumin. This was also confirmed morphologically by modified acridine orange/ethidium bromide staining and fluorescent microscopy. Importantly, nanocarrier NG127 alone displayed practically no cytotoxicity. We conclude that nanogel carriers offer an innovative way to encapsulate curcumin and to obtain more effective anticancer therapeutics than curcumin alone with a potential to specific tumor targeting, such as using antibodies against surface receptors specific to breast cancer cells.
authors.affiliation: Bucknell University, Lewisburg, PA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Reeves
authors.affiliation: University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Serguei V
authors.initials: SV
authors.lastname: Vinogradov
authors.affiliation: Amnis Corporation, Seattle, Washington, National Cancer Institute, NIH, Rockville, Maryland.
authors.forename: Phil
authors.initials: P
authors.lastname: Morrissey
authors.affiliation: Bucknell University, Lewisburg, PA, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Chernin
authors.affiliation: Radiation Research Program, National Cancer Institute, NIH, Rockville, Maryland.
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Ahmed
keywords: Anticancer Drugs And Breast Cancer Cells; Curcumin; Nanogels