PEG-PE/phosphatidylcholine mixed immunomicelles specifically deliver encapsulated taxol to tumor cells of different origin and promote their efficient killing

被引:80
作者
Gao, Z [1 ]
Lukyanov, AN [1 ]
Chakilam, AR [1 ]
Torchilin, VP [1 ]
机构
[1] Northeastern Univ, Bouve Coll Hlth Sci, Dept Pharmaceut Sci, Boston, MA 02115 USA
关键词
immunomicelles; anticancer antibody; taxol (paclictaxel); tumor cell targeting; cytotoxicity;
D O I
10.1080/1061186031000138623
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Mixed micelles were prepared from poly(ethyleneglycol)-distearyl phosphoethanolamine (PEG(2000)-PE) and egg phosphatidylcholine. The micelles were covalently modified with the nucleosome-specific monoclonal antibody 2C5 known to recognize and bind a variety of tumor cells via their surface-bound nucleosomes. Covalent attachment of 2C5 antibody was performed via a micelle-incorporated PEG-PE with the distal terminus of the PEG block activated with p-nitrophenylcarbonyl group (pNP-PEG-PE). Micelle surface-attached 2C5 antibody maintained its specific activity. 2C5-targeted immunomicelles were able to carry more than 3 wt% of taxol. Taxol-loaded immunomicelles specifically recognized tumor cell lines of several types. The cytotoxicity of 2C5-targeted taxol-loaded immunomicelles in a cell culture model was much higher when compared with free taxol or taxol in non-targeted micelles.
引用
收藏
页码:87 / 92
页数:6
相关论文
共 23 条
[1]   A MIXED MICELLAR FORMULATION SUITABLE FOR THE PARENTERAL ADMINISTRATION OF TAXOL [J].
ALKANONYUKSEL, H ;
RAMAKRISHNAN, S ;
CHAI, HB ;
PEZZUTO, JM .
PHARMACEUTICAL RESEARCH, 1994, 11 (02) :206-212
[2]   TAXOL-LIPID INTERACTIONS - TAXOL-DEPENDENT EFFECTS ON THE PHYSICAL-PROPERTIES OF MODEL MEMBRANES [J].
BALASUBRAMANIAN, SV ;
STRAUBINGER, RM .
BIOCHEMISTRY, 1994, 33 (30) :8941-8947
[3]   Poly(ethylene glycol)-human serum albumin-paclitaxel conjugates: preparation, characterization and pharmacokinetics [J].
Dosio, F ;
Arpicco, S ;
Brusa, P ;
Stella, B ;
Cattel, L .
JOURNAL OF CONTROLLED RELEASE, 2001, 76 (1-2) :107-117
[4]   TAXOL (PACLITAXEL) - A NOVEL ANTI-MICROTUBULE AGENT WITH REMARKABLE ANTINEOPLASTIC ACTIVITY [J].
FOA, R ;
NORTON, L ;
SEIDMAN, AD .
INTERNATIONAL JOURNAL OF CLINICAL & LABORATORY RESEARCH, 1994, 24 (01) :6-14
[5]   Diacyllipid-polymer micelles as nanocarriers for poorly soluble anticancer drugs [J].
Gao, ZG ;
Lukyanov, AN ;
Singhal, A ;
Torchilin, VP .
NANO LETTERS, 2002, 2 (09) :979-982
[6]  
HORWITZ SB, 1992, TRENDS PHARMACOL SCI, V13, P134
[7]   ANTINUCLEAR AUTOANTIBODIES OF THE AGED REACTIVE AGAINST THE SURFACE OF TUMOR BUT NOT NORMAL-CELLS [J].
IAKOUBOV, L ;
ROKHLIN, O ;
TORCHILIN, V .
IMMUNOLOGY LETTERS, 1995, 47 (1-2) :147-149
[8]  
Iakoubov LZ, 1997, ONCOL RES, V9, P439
[9]   Polyethylene glycol-diacyllipid micelles demonstrate increased acculumation in subcutaneous tumors in mice [J].
Lukyanov, AN ;
Gao, ZG ;
Mazzola, L ;
Torchilin, VP .
PHARMACEUTICAL RESEARCH, 2002, 19 (10) :1424-1429
[10]   A submicron lipid emulsion coated with amphipathic polyethylene glycol for parenteral administration of paclitaxel (Taxol) [J].
Lundberg, BB .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1997, 49 (01) :16-21