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PMID: 12716967 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Immunomicelles: targeted pharmaceutical carriers for poorly soluble drugs.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 10 ·2003-05-13 ·Pages 6039-44

Torchilin VP, Lukyanov AN, Gao Z, Papahadjopoulos-Sternberg B

Abstract

To prepare immunomicelles, new targeted carriers for poorly soluble pharmaceuticals, a procedure has been developed to chemically attach mAbs to reactive groups incorporated into the corona of polymeric micelles made of polyethylene glycol-phosphatidylethanolamine conjugates. Micelle-attached antibodies retained their ability to specifically interact with their antigens. Immunomicelles with attached antitumor mAb 2C5 effectively recognized and bound various cancer cells in vitro and showed an increased accumulation in experimental tumors in mice when compared with nontargeted micelles. Intravenous administration of tumor-specific 2C5 immunomicelles loaded with a sparingly soluble anticancer agent, taxol, into experimental mice bearing Lewis lung carcinoma resulted in an increased accumulation of taxol in the tumor compared with free taxol or taxol in nontargeted micelles and in enhanced tumor growth inhibition. This family of pharmaceutical carriers can be used for the solubilization and enhanced delivery of poorly soluble drugs to various pathological sites in the body.

MeSH Terms
Animals Antibodies Biological Transport Breast Neoplasms Drug Carriers Drug Design Female Fluoresceins Freeze Fracturing Humans Indium Radioisotopes/pharmacokinetics Kinetics Lung Neoplasms Lymphoma Metabolic Clearance Rate Mice Micelles Microscopy, Electron Phosphatidylethanolamines Polyethylene Glycols Solubility Tumor Cells, Cultured
Chemicals
Antibodies Drug Carriers Fluoresceins Indium Radioisotopes Micelles Phosphatidylethanolamines dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine 6-carboxyfluorescein Polyethylene Glycols
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Torchilin Vladimir P
Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA. v.torchilin@neu.edu
Lukyanov Anatoly N
Gao Zhonggao
Papahadjopoulos-Sternberg Brigitte
References (38)
38 references, click to expand
  1. Preparation, characterization and properties of sterically stabilized paclitaxel-containing liposomes.
    J Control Release. 2000 Jan 3;63(1-2):19-30 PMID: 10640577
  2. Nucleosome-releasing treatment makes surviving tumor cells better targets for nucleosome-specific anticancer antibodies.
    Cancer Detect Prev. 1998;22(5):470-5 PMID: 9727629
  3. p-Nitrophenylcarbonyl-PEG-PE-liposomes: fast and simple attachment of specific ligands, including monoclonal antibodies, to distal ends of PEG chains via p-nitrophenylcarbonyl groups.
    Biochim Biophys Acta. 2001 Apr 2;1511(2):397-411 PMID: 11286983
  4. TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8786-91 PMID: 11438707
  5. Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS.
    J Control Release. 2001 Jul 6;74(1-3):47-61 PMID: 11489482
  6. Tumor targeting using anti-her2 immunoliposomes.
    J Control Release. 2001 Jul 6;74(1-3):95-113 PMID: 11489487
  7. Structure and design of polymeric surfactant-based drug delivery systems.
    J Control Release. 2001 Jun 15;73(2-3):137-72 PMID: 11516494
  8. N-Succinyl-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin: an extracellularly tumor-activated prodrug devoid of intravenous acute toxicity.
    J Med Chem. 2001 Oct 25;44(22):3750-3 PMID: 11606140
  9. Monoclonal antibodies in the treatment of malignancy: basic concepts and recent developments.
    Cancer Invest. 2001;19(8):833-41 PMID: 11768037
  10. Polyethylene glycol-diacyllipid micelles demonstrate increased acculumation in subcutaneous tumors in mice.
    Pharm Res. 2002 Oct;19(10):1424-9 PMID: 12425458
  11. The mechanism of liposome accumulation in infarction.
    Biochim Biophys Acta. 1984 Mar 1;797(3):363-8 PMID: 6365177
  12. Monoclonal antibody to cardiac myosin: imaging of experimental myocardial infarction.
    Hybridoma. 1984;3(1):11-23 PMID: 6469268
  13. Fate and behavior of liposomes in vivo: a review of controlling factors.
    Crit Rev Ther Drug Carrier Syst. 1987;3(2):123-93 PMID: 3542245
  14. Monoclonal antibodies in cancer detection and therapy.
    Am J Med. 1993 Mar;94(3):297-312 PMID: 8452154
  15. Uses and limitations of monoclonal antibodies (MoAbs) in the treatment of malignant disease: a review.
    J R Soc Med. 1993 Apr;86(4):219-24 PMID: 8505732
  16. Taxol dose intensification and its clinical implications.
    J Natl Med Assoc. 1993 Jun;85(6):427-31 PMID: 8103561
  17. Biodegradable long-circulating polymeric nanospheres.
    Science. 1994 Mar 18;263(5153):1600-3 PMID: 8128245
  18. Lipophilic beta-adrenoceptor antagonists and local anesthetics are effective direct activators of G-proteins.
    Biochem Pharmacol. 1994 May 18;47(10):1789-95 PMID: 7911302
  19. Accumulation of protein-loaded long-circulating micelles and liposomes in subcutaneous Lewis lung carcinoma in mice.
    Pharm Res. 1998 Oct;15(10):1552-6 PMID: 9794497
  20. Solubility and stability of tetrazepam in mixed micelles.
    Eur J Pharm Sci. 1998 Dec;7(1):49-55 PMID: 9845777
  21. Polymeric micelles - a new generation of colloidal drug carriers.
    Eur J Pharm Biopharm. 1999 Sep;48(2):101-11 PMID: 10469928
  22. Polyion complex micelles with protein-modified corona for receptor-mediated delivery of oligonucleotides into cells.
    Bioconjug Chem. 1999 Sep-Oct;10(5):851-60 PMID: 10502353
  23. A liposomal MRI contrast agent: phosphatidylethanolamine-DTPA.
    Magn Reson Med. 1989 Aug;11(2):236-43 PMID: 2779414
  24. Stabilization of disulfide linkage in drug-polymer-immunoglobulin conjugate by microenvironmental control.
    Biochem Biophys Res Commun. 1989 Nov 15;164(3):1234-9 PMID: 2590198
  25. The neuroleptic activity of haloperidol increases after its solubilization in surfactant micelles. Micelles as microcontainers for drug targeting.
    FEBS Lett. 1989 Dec 4;258(2):343-5 PMID: 2599097
  26. Relationships in the structure-tissue distribution of basic drugs in the rabbit.
    Pharm Res. 1990 Jul;7(7):691-6 PMID: 2395795
  27. Absorption enhancers.
    Crit Rev Ther Drug Carrier Syst. 1990;7(1):1-33 PMID: 2257635
  28. Mixed micelles in drug delivery.
    Nature. 1992 Jan 16;355(6357):279-80 PMID: 1731228
  29. Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft.
    Cancer Res. 1994 Jul 1;54(13):3352-6 PMID: 8012948
  30. Barriers to drug delivery in solid tumors.
    Sci Am. 1994 Jul;271(1):58-65 PMID: 8066425
  31. Reversed-phase high-performance liquid chromatographic determination of taxol in mouse plasma.
    J Chromatogr B Biomed Appl. 1994 May 13;655(2):315-9 PMID: 7915939
  32. Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size.
    Cancer Res. 1995 Sep 1;55(17):3752-6 PMID: 7641188
  33. Anti-nuclear autoantibodies of the aged reactive against the surface of tumor but not normal cells.
    Immunol Lett. 1995 Jul-Aug;47(1-2):147-9 PMID: 8537094
  34. Poly(ethylene glycol)-coated anti-cardiac myosin immunoliposomes: factors influencing targeted accumulation in the infarcted myocardium.
    Biochim Biophys Acta. 1996 Feb 21;1279(1):75-83 PMID: 8624365
  35. Accumulation of liposomal lipid and encapsulated doxorubicin in murine Lewis lung carcinoma: the lack of beneficial effects by coating liposomes with poly(ethylene glycol).
    J Pharmacol Exp Ther. 1997 Mar;280(3):1319-27 PMID: 9067319
  36. A novel class of antitumor antibodies: nucleosome-restricted antinuclear autoantibodies (ANA) from healthy aged nonautoimmune mice.
    Oncol Res. 1997;9(8):439-46 PMID: 9436197
  37. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment.
    Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4607-12 PMID: 9539785
  38. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review.
    J Control Release. 2000 Mar 1;65(1-2):271-84 PMID: 10699287
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0931428100
Email
v.torchilin@neu.edu
Published
2003-05-13
Epub
2003-00-25
Pages
6039-44
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC156322
Subset
IM
Grants
NIMH NIH HHS · R01 MH060200 · United States
NIGMS NIH HHS · 5R01 GM60200 · United States
External Links
PubMed source DOI: 10.1073/pnas.0931428100 PMC Full Text View journal details
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