Targeted delivery of doxorubicin: drug delivery system based on PAMAM dendrimers.
Polyamidoamine (PAMAM) dendrimers of the second generation (G2) are branched polymers containing 16 surface amino groups that allow them to be used as universal carriers on creating systems for drug delivery. G2 labeled with fluorescein isothiocyanate (FITC) efficiently bound with the surface of tumor cells at 4°C and was absorbed by the cells at 37°C. The covalent binding to G2-FITC of a vector protein, a recombinant fragment of the human alpha-fetoprotein receptor-binding domain (rAFP3D), increased the binding and endocytosis efficiency more than threefold. Covalent conjugates of G2 with doxorubicin (Dox) obtained by acid-labile linking of cis-aconitic anhydride (CAA) without the vector protein (G2-Dox) and with the vector protein rAFP3D (rAFP3D-G2-Dox) were accumulated by the tumor cells with high efficiency. However, a selective effect was observed only in rAFP3D-G2-Dox, which also demonstrated high cytotoxic activity against the human ovarian adenocarcinoma SKOV3 cells and low cytotoxicity against human peripheral blood lymphocytes. Based on these results, rAFP3D-G2 conjugate is promising for selective delivery of antitumor drugs.
Bioengineering Center, Russian Academy of Sciences, Moscow, 117312, Russia. nikita_yabbarov@yahoo.com.
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Yabbarov
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Posypanova
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Vorontsov
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ON
Popova
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Severin
D000230:Adenocarcinoma; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms
D000903:Antibiotics, Antineoplastic; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D004317:Doxorubicin