A new system for targeted delivery of doxorubicin into tumor cells

The use of vector molecules for the targeted delivery of antitumor drugs provides their selectivity for cancer cells. The recombinant receptor-binding fragment of alpha-fetoprotein (rAFP3D) was used as a vector molecule. The specific receptor of alpha-fetoprotein is a universal tumor marker, being e...

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Bibliographic Details
Published in:Journal of controlled release 2013-06, Vol.168 (2), p.135-141
Main Authors: Yabbarov, N.G., Posypanova, G.A., Vorontsov, E.A., Obydenny, S.I., Severin, E.S.
Format: Article
Language:English
Subjects:
Adenocarcinoma
Alpha-fetoprotein
alpha-Fetoproteins - chemistry
antibiotics
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - chemistry
Cell Line, Tumor
Cell Survival - drug effects
cytotoxicity
Dendrimer
Dendrimers - administration & dosage
Dendrimers - chemistry
doxorubicin
Doxorubicin - administration & dosage
Doxorubicin - chemistry
Drug Delivery Systems
Endocytosis
Fluorescein-5-isothiocyanate - chemistry
Humans
lymphocytes
Lymphocytes - metabolism
Multidrug resistance
neoplasm cells
Neoplasms - drug therapy
Neoplasms - metabolism
Targeted delivery
tissues
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Summary:The use of vector molecules for the targeted delivery of antitumor drugs provides their selectivity for cancer cells. The recombinant receptor-binding fragment of alpha-fetoprotein (rAFP3D) was used as a vector molecule. The specific receptor of alpha-fetoprotein is a universal tumor marker, being expressed on the surface of many tumor cells, but not in normal human tissues. And rAFP3D includes the receptor binding cite of AFP. A three-component delivery system including vector protein rAFP3D, PAMAM G2 dendrimer and antitumor antibiotic doxorubicin (Dox) was synthesized. The attachment of two dendrimer molecules to the vector protein did not affect the effectiveness of rAFP3D binding to AFP receptor on the surface of tumor cells nor the effectiveness of receptor-mediated endocytosis. Dox was conjugated with G2 via cis-aconitic anhydride (acid labile linker). The in vitro Dox release study showed that the conjugate was stable at neutral pH but was labile at pH
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2013.03.007