title: Enhanced apoptotic effects of dihydroartemisinin-aggregated gelatin and hyaluronan nanoparticles on human lung cancer cells.
abstract: Recent studies suggest that dihydroartemisinin (DHA), a derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua L., has anticancer properties. Due to poor water solubility, poor oral activity, and a short plasma half-life, large doses of DHA have to be injected to achieve the necessary bioavailability. This study examined increasing DHA bioavailability by encapsulating DHA within gelatin (GEL) or hyaluronan (HA) nanoparticles via an electrostatic field system. Observations from transmission electron microscopy show that DHA in GEL and HA nanoparticles formed GEL/DHA and HA/DHA aggregates that were approximately 30-40 nm in diameter. The entrapment efficiencies for DHA were approximately 13 and 35% for the GEL/DHA and HA/DHA aggregates, respectively. The proliferation of A549 cells was inhibited by the GEL/DHA and HA/DHA aggregates. Fluorescent annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) staining displayed low background staining with annexin V-FITC or PI on DHA-untreated cells. In contrast, annexin V-FITC and PI stains dramatically increased when the cells were incubated with GEL/DHA and HA/DHA aggregates. These results suggest that DHA-aggregated GEL and HA nanoparticles exhibit higher anticancer proliferation activities than DHA alone in A549 cells most likely due to the greater aqueous dispersion after hydrophilic GEL or HA nanoparticles aggregation. These results demonstrate that DHA can aggregate with nanoparticles in an electrostatic field environment to form DHA nanosized aggregates.
authors.affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.forename: Benjamin
authors.initials: B
authors.lastname: Teong
authors.forename: I-Fen
authors.initials: IF
authors.lastname: Chen
authors.forename: Shwu Jen
authors.initials: SJ
authors.lastname: Chang
authors.forename: Jimin
authors.initials: J
authors.lastname: Gao
authors.forename: Shyh-Ming
authors.initials: SM
authors.lastname: Kuo
mesh_terms: D020341:Absorbable Implants; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D004337:Drug Carriers; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010316:Particle Size; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D037621:Artemisinins; D004396:Coloring Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D013778:Tetrazolium Salts; D013844:Thiazoles; C039060:artenimol; D005780:Gelatin; D006820:Hyaluronic Acid; C022616:thiazolyl blue; D016650:Fluorescein-5-isothiocyanate
keywords: aggregates; dihydroartemisinin; gelatin; hyaluronan; nanoparticles