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Folding graft copolymer with pendant drug segment for co-delivery of anticancer drugs

Authors
Journal
Biomaterials
0142-9612
Publisher
Elsevier
Volume
35
Issue
25
Identifiers
DOI: 10.1016/j.biomaterials.2014.05.004
Keywords
  • Graft Copolymer
  • Micelle
  • Combination Therapy
  • Folding
  • Ring Open Polymerization
Disciplines
  • Biology

Abstract

Abstract A graft copolymer with pendant drug segment can fold into nanostructures in a protein folding-like manner. The graft copolymer is constructed by directly polymerizing γ-camptothecin-glutamate N-carboxyanhydride (Glu(CPT)-NCA) on multiple sites of poly(ethylene glycol) (PEG)-based main chain via the ring open polymerization (ROP). The “purely” conjugated anticancer agent camptothecin (CPT) is hydrophobic and serves as the principal driving force during the folding process. When exposed to water, the obtained copolymer, together with doxorubicin (Dox), another anticancer agent, can fold into monodispersed nanocarriers (with a diameter of around 50 nm) for dual-drug delivery. Equipped with a PEG shell, the nanocarriers displayed good stability and can be internalized by a variety of cancer cell lines via the lipid raft and clathrin-mediated endocytotic pathway without premature leakage, which showed a high synergetic activity of CPT and Dox toward various cancer cells. In vivo study validated that the nanocarriers exhibited strong accumulation in tumor sites and showed a prominent anticancer activity against the lung cancer xenograft mice model compared with free drugs.

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