title: Liposomal quercetin efficiently suppresses growth of solid tumors in murine models.
abstract: OBJECTIVE
  Quercetin is a potent chemotherapeutic drug. Clinical trials exploring different schedules of administration of quercetin have been hampered by its extreme water insolubility. To overcome this limitation, this study is aimed to develop liposomal quercetin and investigate its distribution in vivo and antitumor efficacy in vivo and in vitro.
  
  
  METHODS
  Quercetin was encapsulated in polyethylene glycol 4000 liposomes. Biodistribution of liposomal quercetin i.v. at 50 mg/kg in tumor-bearing mice was detected by high-performance liquid chromatography. Induction of apoptosis by liposomal quercetin in vitro was tested. The antitumor activity of liposomal quercetin was evaluated in the immunocompetent C57BL/6N mice bearing LL/2 Lewis lung cancer and in BALB/c mice bearing CT26 colon adenocarcinoma and H22 hepatoma. Tumor volume and survival time were observed. The mechanisms underlying the antitumor effect of quercetin in vivo was investigated by detecting the microvessel density, apoptosis, and heat shock protein 70 expression in tumor tissues.
  
  
  RESULTS
  Liposomal quercetin could be dissolved in i.v. injection and effectively accumulate in tumor tissues. The half-time of liposomal quercetin was 2 hours in plasma. The liposomal quercetin induced apoptosis in vitro and significantly inhibited tumor growth in vivo in a dose-dependent manner. The optimal dose of liposomal quercetin resulted in a 40-day survival rate of 40%. Quantitative real-time PCR showed that liposomal quercetin down-regulated the expression of heat shock protein 70 in tumor tissues. Immunohistochemistry analysis showed that liposomal quercetin inhibited tumor angiogenesis as assessed by CD31 and induced tumor cell apoptosis.
  
  
  CONCLUSIONS
  Our data indicated that pegylated liposomal quercetin can significantly improve the solubility and bioavailability of quercetin and can be a potential application in the treatment of tumor.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Zhi-ping
authors.initials: ZP
authors.lastname: Yuan
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Chen
authors.forename: Lin-yu
authors.initials: LY
authors.lastname: Fan
authors.forename: Ming-hai
authors.initials: MH
authors.lastname: Tang
authors.forename: Guang-li
authors.initials: GL
authors.lastname: Yang
authors.forename: Han-su
authors.initials: HS
authors.lastname: Yang
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Du
authors.forename: Guo-qing
authors.initials: GQ
authors.lastname: Wang
authors.forename: Wen-xiu
authors.initials: WX
authors.lastname: Yao
authors.forename: Qu-mei
authors.initials: QM
authors.lastname: Zhao
authors.forename: Bin
authors.initials: B
authors.lastname: Ye
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Diao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hong-bin
authors.initials: HB
authors.lastname: Wu
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Yu-quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004337:Drug Carriers; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D007275:Injections, Intravenous; D008081:Liposomes; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols; D011794:Quercetin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012995:Solubility; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D004337:Drug Carriers; D018840:HSP70 Heat-Shock Proteins; D008081:Liposomes; D011092:Polyethylene Glycols; D011794:Quercetin