title: N-(2-Hydroxypropyl)methacrylamide-based polymer conjugates with pH-controlled activation of doxorubicin for cell-specific or passive tumour targeting. Synthesis by RAFT polymerisation and physicochemical characterisation.
abstract: Controlled radical reversible addition-fragmentation chain transfer (RAFT) polymerisation was used to prepare water-soluble polymer-drug carriers based on copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) with a hydrazide group-containing monomer, showing well-defined structure with narrow molecular weight distribution (approx. 1.1-1.2). The anticancer therapeutic doxorubicin was bound to the polymeric carrier by a hydrazone bond, enabling pH-controlled release under mildly acid conditions that mimics the environment in endosomes/lysosomes of tumour cells. RAFT polymerisation facilitated the synthesis of semitelechelic copolymers, which were used in the synthesis of monoclonal anti-CD20 antibody-polymer-drug conjugate designed for cell-specific tumour targeting. They were also used for producing a biodegradable high-molecular-weight graft polymer-drug conjugate that degrade in the presence of glutathione, which is designed for passive targeting to solid tumours. The conjugates exhibited well-defined structures with narrow molecular weight distributions of approx. 1.3 and pH-controlled drug release.
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague 6, Czech Republic. chytil@imc.cas.cz
authors.forename: Petr
authors.initials: P
authors.lastname: Chytil
authors.forename: Tomáš
authors.initials: T
authors.lastname: Etrych
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kříž
authors.forename: Vladimír
authors.initials: V
authors.lastname: Subr
authors.forename: Karel
authors.initials: K
authors.lastname: Ulbrich
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015394:Molecular Structure; D058105:Polymerization
chemical_list: D000178:Acrylamides; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D004317:Doxorubicin; C032976:N-(2-hydroxypropyl)methacrylamide