title: Enhanced cytotoxicity of a polymer-drug conjugate with triple payload of paclitaxel.
abstract: The development of targeting approaches to selectively release chemotherapeutic drugs into malignant tissue is a major challenge in anticancer therapy. We have synthesized an N-(2-hydroxypropyl)-methacrylamide (HPMA) copolymer-drug conjugate with an AB(3) self-immolative dendritic linker. HPMA copolymers are known to accumulate selectively in tumors. The water-soluble polymer-drug conjugate was designed to release a triple payload of the hydrophobic drug paclitaxel as a result of cleavage by the endogenous enzyme cathepsin B. The polymer-drug conjugate exhibited enhanced cytotoxicity on murine prostate adenocarcinoma (TRAMP C2) cells in comparison to a classic monomeric drug-polymer conjugate.
authors.affiliation: Department of Organic Chemistry, School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Rotem
authors.initials: R
authors.lastname: Erez
authors.forename: Ehud
authors.initials: E
authors.lastname: Segal
authors.forename: Keren
authors.initials: K
authors.lastname: Miller
authors.forename: Ronit
authors.initials: R
authors.lastname: Satchi-Fainaro
authors.forename: Doron
authors.initials: D
authors.lastname: Shabat
mesh_terms: D000178:Acrylamides / Q000008:administration & dosage* / Q000737:chemistry; D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D008297:Male; D051379:Mice; D017239:Paclitaxel; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D050091:Dendrimers; D011355:Prodrugs; D017239:Paclitaxel; C032976:N-(2-hydroxypropyl)methacrylamide