title: Influence of coupling bonds on the anti-tumor activity of polymer-pirarubicin conjugates.
abstract: Pirarubicin (THP) was conjugated onto the pendant carboxyl groups of poly(ethylene glycol)-block-poly(l-lactide-co-2-methyl-2-carboxyl-propylene carbonate) [PEG-b-P(LA-co-MCC)] through hydrazone, ester, and amide bonds, respectively, and the conjugates were assembled into micelles with diameters between 30 and 60 nm. The in vitro THP release of the three conjugate micelles was conducted in pH 7.4 and 5.0 buffer solutions, and conjugate micelles with hydrazone linkage had the fastest THP release rate. Their in vitro cytotoxicity was tested using mouse mammary adenocarcinoma EMT6 cells and in vivo anti-tumor activity in Balb/c mice models bearing EMT6 tumors were compared with free THP and with each other. The results showed that the polymer-THP conjugates displayed higher cell-uptakes and better anti-tumor activities than free THP at 4h, and among the three micelles, those with hydrazone linkage had the highest anti-tumor activity in vivo, while those with amide linkage were the lowest.
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Mo
authors.forename: Xiuli
authors.initials: X
authors.lastname: Hu
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Yue
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Yubin
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004952:Esters / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011407:Propane / Q000031:analogs & derivatives / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000577:Amides; D000903:Antibiotics, Antineoplastic; D004952:Esters; D006835:Hydrazones; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D011092:Polyethylene Glycols; C033616:poly(lactide); D004317:Doxorubicin; C045990:propylene carbonate; C027260:pirarubicin; D011407:Propane