Drug-loaded, bivalent-bottle-brush polymers by graft-through ROMP.

Drug-loaded, bivalent-bottle-brush polymers by graft-through ROMP.
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DOI:
10.1021/ma1021506
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发表时间:
2010-12-28
期刊:
影响因子:
5.5
通讯作者:
Grubbs RH
Grubbs RH
中科院分区:
化学1区
文献类型:
--
作者:
Johnson JA;Lu YY;Burts AO;Xia Y;Durrell AC;Tirrell DA;Grubbs RH

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Graft-through ring-opening metathesis polymerization (ROMP) using ruthenium N-heterocyclic carbene catalysts has enabled the synthesis of bottle-brush polymers with unprecedented ease and control. Here we report the first bivalent-brush polymers; these materials were prepared by graft-through ROMP of drug-loaded polyethylene-glycol (PEG) based macromonomers (MMs). Anticancer drugs doxorubicin (DOX) and camptothecin (CT) were attached to a norbornene-alkyne-PEG MM via a photocleavable linker. ROMP of either or both drug-loaded MMs generated brush homo- and co-polymers with low polydispersities and defined molecular weights. Release of free DOX and CT from these materials was initiated by exposure to 365 nm light. All of the CT and DOX polymers were at least 10-fold more toxic to human cancer cells after photoinitiated drug release while a copolymer carrying both CT and DOX displayed 30-fold increased toxicity upon irradiation. Graft-through ROMP of drug-loaded macromonomers provides a general method for the systematic study of structure-function relationships for stimuli-responsive polymers in biological systems.
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