title: Improved antitumor activity of epirubicin-loaded CXCR4-targeted polymeric nanoparticles in liver cancers.
abstract: A liver-targeted drug delivery system (CX-EPNP) composed of PLGA/TPGS was prepared and characterized. The surface of nanoparticle was conjugated with LFC131 peptide to increase the specific interaction of carrier with CXCR4 overexpressing liver cancers to enhance the Epirubicin (EPI) delivery to tumors. The particles were nanosized with size than 150 nm and portrayed a sustained release kinetics suggesting its suitability for cancer targeting. The in vitro cell uptake results showed that the introduction of LFC131 to the nanoparticles could increase significantly the affinity to human hepatic carcinoma cells (HepG2) with approximately a 3-fold improvement in cellular uptake than non-targeted one. A specific receptor-mediated uptake was observed by confocal laser scanning microscopy. In addition, CX-EPNP showed remarkable cytotoxicity towards HepG2 cells, and could effectively inhibit tumor growth. The more significant EPI accumulation from CX-EPNP in the cancer cells gave rise to the enhanced EPI cytotoxicity and cell apoptosis. The CX-EPNP distributed mostly in the xenograft tumor after intravenous administration to mice and adequately remained in the blood for at least 24h. It seemed that CX-EPNP upon intravenous injection avoided rapid recognition by Kupffer cells and adequately remained in the blood. These findings suggest that CX-EPNP could effectively inhibit the growth of liver tumors in situ and could potentially reduce the systemic side effects. However, extensive investigation is still needed to assess the possible applications of the CX-EPNP in humans.
authors.affiliation: Department of Hepatobiliary Surgery, Shengli Oilfield Central Hospitial, 31 Jinan Road, Dongying, Shandong Province 257000, PR China.
authors.forename: Sun
authors.initials: S
authors.lastname: Di-Wen
authors.affiliation: Department of Hepatobiliary Surgery, Shengli Oilfield Central Hospitial, 31 Jinan Road, Dongying, Shandong Province 257000, PR China.
authors.forename: Guo-Zheng
authors.initials: GZ
authors.lastname: Pan
authors.affiliation: Department of Hepatobiliary Surgery, Shengli Oilfield Central Hospitial, 31 Jinan Road, Dongying, Shandong Province 257000, PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Hepatobiliary Surgery, Shengli Oilfield Central Hospitial, 31 Jinan Road, Dongying, Shandong Province 257000, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Shengli Oilfield Central Hospitial, 31 Jinan Road, Dongying, Shandong Province 257000, PR China.
authors.forename: Qing-Ze
authors.initials: QZ
authors.lastname: Xue
authors.affiliation: Department of Hepatobiliary Surgery, Shengli Oilfield Central Hospitial, 31 Jinan Road, Dongying, Shandong Province 257000, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, Shengli Oilfield Central Hospitial, 31 Jinan Road, Dongying, Shandong Province 257000, PR China. Electronic address: yuanqingzhong@hotmail.com.
authors.forename: Qing-Zhong
authors.initials: QZ
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D065546:Drug Liberation; D015251:Epirubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000648:ultrastructure; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016896:Treatment Outcome; D014810:Vitamin E / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015251:Epirubicin; C014225:tocophersolan
keywords: Biodistribution; CXCR4; Epirubicin; Liver cancer; Targeted nanoparticles