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

Abstract
A graft copolymer with pendant drug segments 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.
AuthorsWanyi Tai, Ran Mo, Yue Lu, Tianyue Jiang, Zhen Gu
JournalBiomaterials (Biomaterials) Vol. 35 Issue 25 Pg. 7194-203 (Aug 2014) ISSN: 1878-5905 [Electronic] Netherlands
PMID24875756 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightPublished by Elsevier Ltd.
Chemical References
  • Antineoplastic Agents
  • Drug Carriers
  • Micelles
  • Polymers
  • Polyethylene Glycols
  • Doxorubicin
  • Camptothecin
Topics
  • Animals
  • Antineoplastic Agents (chemistry, pharmacology)
  • Camptothecin (chemistry, pharmacology)
  • Cell Line, Tumor
  • Doxorubicin (chemistry, pharmacology)
  • Drug Carriers (chemistry)
  • Endocytosis (drug effects)
  • Female
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Mice
  • Mice, Nude
  • Micelles
  • Nanostructures (chemistry)
  • Polyethylene Glycols (chemistry)
  • Polymers (chemistry)
  • Xenograft Model Antitumor Assays

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