title: Functional alginate nanoparticles for efficient intracellular release of doxorubicin and hepatoma carcinoma cell targeting therapy.
abstract: In order to efficiently deliver chemotherapy drugs into hepatoma cells, a pH-sensitive and liver-targeted drug delivery system (glycyrrhetinic acid-modified alginate/doxorubicin-modified alginate complex nanoparticles), termed GA-ALG/DOX-ALG NPs, was prepared. First, GA-ALG and DOX-ALG were synthesized, and then GA-ALG/DOX-ALG NPs self-assembled by mixing GA-ALG and DOX-ALG via dialysis. Properties of pH-sensitivity, biodistribution in mice, and antitumor activity against ectopic hepatoma tumors in the NPs were evaluated. DOX release from GA-ALG/DOX-ALG NPs showed pH-sensitivity; less than 10% of drugs were liberated at pH 7.4 within 9 d while 58.7% of DOX released at pH 4.0. The confocal laser scanning microscope (CLSM) experiment showed that GA-ALG/DOX-ALG NPs can respond to the endosomal/lysosomal environment and had pH-triggered intracellular releasing property. The area under the curve (AUC(0-∞)) and half-life (t(½)) in the liver of GA-ALG/DOX-ALG NPs were 1156.7 μg h/g and 34.3 h, respectively, which was 11.8- and 3.2-fold higher than that of the DOX·HCl group. Furthermore, the inhibition rate of tumor growth was 79.3% after treatment with GA-ALG/DOX-ALG NPs, which was much higher than that of the DOX·HCl (48.5%) and DOX-ALG NPs groups (62.7%). Importantly, no mice died in the GA-ALG/DOX-ALG NPs group, while the mortality rate was 40% in the DOX·HCl group.
authors.affiliation: Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.forename: Quanyong
authors.initials: Q
authors.lastname: Lai
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wu
authors.forename: Chuangnian
authors.initials: C
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006207:Half-Life; D056945:Hep G2 Cells; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000464:Alginates; D000903:Antibiotics, Antineoplastic; D006603:Hexuronic Acids; D004317:Doxorubicin; D020723:Glucuronic Acid