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.
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Authors | Manju Saraswathy, Gavin T Knight, Srikanth Pilla, Randolph S Ashton, Shaoqin Gong |
Journal | Colloids and surfaces. B, Biointerfaces
(Colloids Surf B Biointerfaces)
Vol. 126
Pg. 590-597
(Feb 01 2015)
ISSN: 1873-4367 [Electronic] Netherlands |
PMID | 25591850
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 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
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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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