Drug targeting by macromolecules without recognition unit?
his review will summarize available information on the ability of macromolecular conjugates containing no specific recognition motifs to deliver anthracyclines (daunomycin, adriamycin) or methotrexate to target cells such as tumour cells or macrophages. Conjugates with natural (proteins, DNA, carbohydrates) and synthetic macromolecules (linear and branched chain poly-alpha-amino acids, non-biodegradable DIVEMA, HPMA etc.) will be reviewed. Experimental data from several laboratories indicate that these conjugates are taken up by cells mainly by fluid-phase or adsorptive endocytosis. It is believed that these processes do not involve 'specific receptors'. Two examples of methotrexate and daunomycin conjugates will be discussed to show the effect of the chemical structure of branched chain polypeptides on the uptake and antitumour or antiparasitic (Leishmania donovani infection) efficacy of conjugates.
Hudecz
Ferenc
F
Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L University, Budapest, Hungary. hudecz@szerves.chem.elte.hu
Reményi
Judit
J
Szabó
Rita
R
Kóczán
György
G
Mezo
Gábor
G
Kovács
Péter
P
Gaál
Dezso
D
D000818:Animals; D018943:Anthracyclines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003630:Daunorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate; D003630:Daunorubicin