title: 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.
authors.affiliation: Department of Biomedical Engineering and Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Manju
authors.initials: M
authors.lastname: Saraswathy
authors.affiliation: Department of Biomedical Engineering and Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Gavin T
authors.initials: GT
authors.lastname: Knight
authors.affiliation: Department of Biomedical Engineering and Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Pilla
authors.affiliation: Department of Biomedical Engineering and Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Randolph S
authors.initials: RS
authors.lastname: Ashton
authors.affiliation: Department of Biomedical Engineering and Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Shaoqin
authors.initials: S
authors.lastname: Gong
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013329:Structure-Activity Relationship; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010456:Peptides, Cyclic; C531249:Poly(amidoamine); D011073:Polyamines; D047392:beta-Cyclodextrins; C507169:cyclic arginine-glycine-aspartic acid peptide; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Drug loading; PAMAM dendrimer; Targeted delivery; cRGD; β-Cyclodextrin