Journal
MACROMOLECULAR BIOSCIENCE
Volume 15, Issue 6, Pages 839-850Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.201400510
Keywords
drug delivery systems; HPMA copolymers; pH-controlled release; reversible addition fragmentation chain transfer (RAFT); star copolymers
Funding
- Czech Science Foundation GACR [P207/11/P551, P207/12/J030]
- Ministry of Education, Youth and Sports of the Czech Republic [EE2.3.30.0029]
- BIOCEV - Biotechnology and Biomedicine Centre of Academy of Sciences [CZ.1.05/1.1.00/02.0109]
- Charles University from European Regional Development Fund
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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 M-w values ranging from 210(5) to 610(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.
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