title: Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles.
abstract: Garcinia mangostana Linn extract (GME) is a natural product that has received considerable attention in cancer therapy, and has the potential to reduce side effects of chemotherapeutics and improve efficacy. We formulated GME-encapsulated ethyl cellulose (GME-EC) and a polymer blend of ethyl cellulose and methyl cellulose (GME-EC/MC) nanoparticles. We achieved high drug-loading and encapsulation efficiency using a solvent-displacement method with particle sizes around 250 nm. Cellular uptake and accumulation of GME was higher for GME-encapsulated nanoparticles compared to free GME. In vitro cytotoxicity analysis showed effective anticancer activity of GME-EC and GME-EC/MC nanoparticles in HeLa cells in a dose-dependent manner. GME-EC/MC nanoparticles showed approximately twofold-higher anticancer activity compared to GME-EC nanoparticles, likely due to their enhanced bioavailability. GME-encapsulated nanoparticles primarily entered HeLa cells by clathrin-mediated endocytosis and trafficked through the endolysosomal pathway. As far as we know, this is the first report on the cellular uptake and intracellular trafficking mechanism of drug-loaded cellulose-based nanoparticles. In summary, encapsulation of GME using cellulose-derivative nanoparticles - GME-EC and GME-EC/MC nanoparticles - successfully improved the bioavailability of GME in aqueous solution, enhanced cellular uptake, and displayed effective anticancer activity.
authors.affiliation: Program in Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand ; Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Porntip
authors.initials: P
authors.lastname: Pan-In
authors.affiliation: Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand ; Nanotec-CU Center of Excellence on Food and Agriculture, Bangkok, Thailand.
authors.forename: Supason
authors.initials: S
authors.lastname: Wanichwecharungruang
authors.affiliation: Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA ; Department of Ophthalmology, Biomedical Engineering, Chemical and Biomolecular Engineering, Neurosurgery, and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
authors.affiliation: Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA ; Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA ; Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004705:Endocytosis / Q000187:drug effects; D029762:Garcinia mangostana / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008747:Methylcellulose / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; C013517:ethyl cellulose; D002482:Cellulose; D008747:Methylcellulose
keywords: cancer; cellulose; intracellular trafficking; nanoparticles; phytotherapy