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Multifunctional drug nanocarriers formed by cRGD-conjugated βCD-PAMAM-PEG for targeted cancer therapy.

Abstract
Polyamidoamine (PAMAM) dendrimer was conjugated with both carboxymethyl-β-cyclodextrin (βCD) and poly(ethylene glycol) (PEG). Cyclic RGD peptide, used as a tumor targeting ligand, was then selectively conjugated onto the distal ends of the PEG arms. The resulting βCD-PAMAM-PEG-cRGD polymer was able to form stable and uniform nanoparticles (NPs) in aqueous solution. Doxorubicin (Dox), a model hydrophobic anticancer drug, was effectively encapsulated in the NPs via an inclusion complex formed between the drug and βCD. The Dox loading level was 16.8 wt%. The cellular uptake of cRGD-conjugated Dox-loaded NPs in the U87MG cell line was much higher than that of non-targeted NPs. Furthermore, the anti-proliferative effect of the cRGD-conjugated NPs was superior to that of free drug and non-targeted NPs. These results suggest that NPs formed by βCD-PAMAM-PEG-cRGD with a high drug payload may significantly improve the anticancer efficacy by tumor-targeted delivery and enhanced cellular uptake.
AuthorsManju Saraswathy, Gavin T Knight, Srikanth Pilla, Randolph S Ashton, Shaoqin Gong
JournalColloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 126 Pg. 590-597 (Feb 01 2015) ISSN: 1873-4367 [Electronic] Netherlands
PMID25591850 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Drug Carriers
  • Peptides, Cyclic
  • Poly(amidoamine)
  • Polyamines
  • beta-Cyclodextrins
  • cyclic arginine-glycine-aspartic acid peptide
  • Polyethylene Glycols
  • Doxorubicin
Topics
  • Antineoplastic Agents (chemistry, pharmacology)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Dose-Response Relationship, Drug
  • Doxorubicin (administration & dosage, chemistry, pharmacology)
  • Drug Carriers (chemical synthesis, chemistry)
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Nanostructures (chemistry)
  • Peptides, Cyclic (chemistry)
  • Polyamines (chemistry)
  • Polyethylene Glycols (chemistry)
  • Structure-Activity Relationship
  • beta-Cyclodextrins (chemistry)

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