Synthesis and Properties of Star HPMA Copolymer Nanocarriers Synthesised by RAFT Polymerisation Designed for Selective Anticancer Drug Delivery and Imaging.
High-molecular-weight star polymer drug nanocarriers intended for the treatment and/or visualisation of solid tumours were synthesised, and their physico-chemical and preliminary in vitro biological properties were determined. The water-soluble star polymer carriers were prepared by the grafting of poly(amido amine) (PAMAM) dendrimers by hetero-telechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, synthesised by the controlled radical Reversible Addition Fragmentation chain Transfer (RAFT) polymerisation. The well-defined star copolymers with Mw values ranging from 2 · 10(5) to 6 · 10(5) showing a low dispersity (approximately 1.2) were prepared in a high yield. A model anticancer drug, doxorubicin, was bound to the star polymer through a hydrazone bond, enabling the pH-controlled drug release in the target tumour tissue. The activated polymer arm ends of the star copolymer carrier enable a one-point attachment for the targeting ligands and/or a labelling moiety. In this study, the model TAMRA fluorescent dye was used to prove the feasibility of the polymer carrier visualisation by optical imaging in vitro. The tailor-made structure of the star polymer carriers should facilitate the synthesis of targeted polymer-drug conjugates, even polymer theranostics, for simultaneous tumour drug delivery and imaging.
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, v.v.i. Heyrovsk, ý, Sq. 2, 162 06, Prague 6, Czech Republic. chytil@imc.cas.cz.
Petr
P
Chytil
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, v.v.i. Heyrovsk, ý, Sq. 2, 162 06, Prague 6, Czech Republic.
Eva
E
Koziolová
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, v.v.i. Heyrovsk, ý, Sq. 2, 162 06, Prague 6, Czech Republic.
Olga
O
Janoušková
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, v.v.i. Heyrovsk, ý, Sq. 2, 162 06, Prague 6, Czech Republic.
Libor
L
Kostka
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, v.v.i. Heyrovsk, ý, Sq. 2, 162 06, Prague 6, Czech Republic.
Karel
K
Ulbrich
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, v.v.i. Heyrovsk, ý, Sq. 2, 162 06, Prague 6, Czech Republic.
Tomáš
T
Etrych
D000818:Animals; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008689:Methacrylates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D003692:Delayed-Action Preparations; D050091:Dendrimers; D008689:Methacrylates; C104700:PAMAM Starburst; D004317:Doxorubicin; C032802:hydroxypropyl methacrylate
HPMA copolymers; drug delivery systems; pH-controlled release; reversible addition fragmentation chain transfer (RAFT); star copolymers