02091nas a2200301   4500008004100000022001400041245011200055210006900167260001500236300001100251490000800262520118800270653001201458653002701470653002501497653002101522653001601543653001101559653001401570653000901584653001401593653001601607100002501623700002401648700003201672700002701704856005801731       2004                        eng d  a0168-365900aTumor-targeted liposomes: doxorubicin-loaded long-circulating liposomes modified with anti-cancer antibody.0 aTumortargeted liposomes doxorubicinloaded longcirculating liposo  c2004 Nov 5  a135-440 v1003 a<p>Commercially available doxorubicin-loaded long-circulating liposomes (Doxil, Alza Pharmaceuticals) were modified with the monoclonal nucleosome (NS)-specific 2C5 antibody (mAb 2C5) that recognizes a broad variety of tumors via the tumor cell surface-bound NSs. For incorporation into liposomes, mAb 2C5 was modified with poly(ethylene glycol)-phosphatidyl ethanolamine conjugate (PEG-PE) with the free PEG terminus activated with the p-nitrophenylcarbonyl group (pNP-PEG-PE). Derivatives of mAb 2C5 containing a variable number of PEG-PE residues (10-32) per protein molecule were prepared with a reasonably good preservation of the antibody specific activity even at the highest degree of modification. PEG-PE-modified antibody quantitatively incorporated into the liposomal membrane of doxorubicin-loaded liposomes with a loss of not more than 20% of the encapsulated doxorubicin. 2C5-targeted Doxil liposomes acquired the ability to recognize NSs and specifically bind to various tumor cells. Doxorubicin-loaded long-circulating liposomes modified with the mAb 2C5 kill various tumor cells in vitro with the efficiency higher than non-targeted doxorubicin-loaded liposomes.</p>10aAnimals10aAntibodies, Monoclonal10aAntibodies, Neoplasm10aCell Line, Tumor10aDoxorubicin10aHumans10aLiposomes10aMice10aNeoplasms10aNucleosomes1 aLukyanov, Anatoly, N1 aElbayoumi, Tamer, A1 aChakilam, Ananthsrinivas, R1 aTorchilin, Vladimir, P  uhttp://www.microfluidicsciences.com/drupal/?q=node/16