title: Resveratrol-loaded polymeric nanoparticles suppress glucose metabolism and tumor growth in vitro and in vivo.
abstract: Resveratrol (RSV) is a natural phenol with promising anti-tumor activities, but its use for in vivo cancer treatment is limited by low aqueous solubility and poor stability. In this study, we prepared RSV-loaded polyethylene glycol-polylactic acid (PEG-PLA; M.W. 5000-5000) polymer nanoparticles (NPs) for improved stability and controlled delivery, and investigated its metabolic and anti-tumor effect in vitro and in vivo. CT26 colon cancer cells displayed significantly reduced cell number to 5.6% and colony forming capacity to 6.3% of controls by 72 h treatment with 40 and 20 μM of RSV-NP, respectively. Flow cytometry and western blots demonstrated increased apoptotic cell death, and (18)F FDG uptake and reactive oxygen species was significantly reduced by RSV-NP. All of these effects were comparable to or greater in potency compared to free RSV. When RSV-NP was intravenously administered to CT26 tumor bearing mice, there was a reduction of (18)F FDG uptake on PET/CT by day 4. Longer treatment led to retardation of tumor growth accompanied by an improvement in survival compared to empty NP-injected controls. These results demonstrate that the in vitro and in vivo metabolic and anti-tumor effects of RSV is preserved by PEG-PLA NP loading, and provide an encouraging outlook on the potential of polymeric NPs as an effective method to deliver RSV for cancer therapy.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Samsung Biomedical Research Institute, Seoul, South Korea.
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Cung Hoa Thien
authors.initials: CHT
authors.lastname: Quach
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Samsung Biomedical Research Institute, Seoul, South Korea. Electronic address: khnm.lee@samsung.com.
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D065546:Drug Liberation; D005947:Glucose / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D005947:Glucose; D000077185:Resveratrol
keywords: Anticancer effect; Glucose metabolism; PEG–PLA; Resveratrol