Targetability of novel immunoliposomes modified with amphipathic poly(ethylene glycol) s conjugated at their distal terminals to monoclonal antibodies

Kazuo Maruyama, Tomoko Takizawa, Tsutomu Yuda, Stephen Kennel, Leaf Huang, Motoharu Iwatsuru

Research output: Contribution to journalArticle

229 Citations (Scopus)

Abstract

Distearoyl-N-(3-carboxypropionoyl poly(ethylene glycol) succinyl)phosphatidylethanolamine (DSPE-PEG-COOH) was newly synthesized and used to prepare novel immunoliposomes carrying monoclonal antibodies at the distal ends of the PEG chains (Type C). Liposomes were prepared from egg phosphatidylcholine (ePC) and cholesterol (CH) (2:1, m/m) containing 6 mol% of DSPE-PEG-COOH, and a monoclonal IgG antibody, 34A, which is highly specific to pulmonary endothelial cells, was conjugated to the carboxyl groups of DSPE-PEG-COOH to give various amounts of antibody molecules per liposome. Other immunoliposomes with PEG coating (Type B) or without PEG coating (an earlier type of immunoliposome, Type A) were prepared for comparison. The average molecular weight of PEG in Type B or C immunoliposomes was 2000. Type B and Type C liposomes without antibodies showed prolonged circulation time and reduced reticulo-endothelial system (RES) uptake owing to the presence of PEG. These three different types of 34A-immunoliposomes with 30-35 antibody molecules per vesicle were injected into mice to test the immunotargetability to the lung. The efficiency of lung binding of 34A-Type B was one-half of that of 34A-Type A, though a large amount of 34A-Type B remained in the blood circulation for a long time, suggesting that the steric hindrance of PEG chains reduced not only the immunospecific antibody-antigen binding, but also the RES uptake. The degree of lung binding of 34A-Type C was about 1.3-fold higher than that of 34A-Type A, indicating that recognition by the antibodies attached to the PEG terminal was not sterically hindered and that the free PEG (i.e., that not carrying antibody) was effective in increasing the blood concentration of immunoliposomes by enabling them to evade RES uptake. The latter phenomenon was confirmed by using nonspecific antibody-Type C immunoliposomes (14-Type C), which showed a high blood level for a long time. Our approach provides a simple means of conjugating antibodies directly to the distal end of PEG which is already bound to the liposome membrane, and should contribute to the development of superior targetable drug delivery vehicles for use in diagnostics and therapy.

Original languageEnglish (US)
Pages (from-to)74-80
Number of pages7
JournalBBA - Biomembranes
Volume1234
Issue number1
DOIs
StatePublished - Mar 8 1995

Fingerprint

Ethylene Glycol
Polyethylene glycols
Monoclonal Antibodies
Antibodies
Liposomes
Lung
Blood
Blood Circulation
Coatings
Phosphatidylcholines
Molecules
Monoclonal antibodies
Ovum
Endothelial cells
Hemodynamics
Drug delivery
Endothelial Cells
Immunoglobulin G
Molecular Weight
Cholesterol

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biophysics
  • Cell Biology

Cite this

Targetability of novel immunoliposomes modified with amphipathic poly(ethylene glycol) s conjugated at their distal terminals to monoclonal antibodies. / Maruyama, Kazuo; Takizawa, Tomoko; Yuda, Tsutomu; Kennel, Stephen; Huang, Leaf; Iwatsuru, Motoharu.

In: BBA - Biomembranes, Vol. 1234, No. 1, 08.03.1995, p. 74-80.

Research output: Contribution to journalArticle

Maruyama, Kazuo ; Takizawa, Tomoko ; Yuda, Tsutomu ; Kennel, Stephen ; Huang, Leaf ; Iwatsuru, Motoharu. / Targetability of novel immunoliposomes modified with amphipathic poly(ethylene glycol) s conjugated at their distal terminals to monoclonal antibodies. In: BBA - Biomembranes. 1995 ; Vol. 1234, No. 1. pp. 74-80.
@article{d322ee83d3d2497688c7c990995154fc,
title = "Targetability of novel immunoliposomes modified with amphipathic poly(ethylene glycol) s conjugated at their distal terminals to monoclonal antibodies",
abstract = "Distearoyl-N-(3-carboxypropionoyl poly(ethylene glycol) succinyl)phosphatidylethanolamine (DSPE-PEG-COOH) was newly synthesized and used to prepare novel immunoliposomes carrying monoclonal antibodies at the distal ends of the PEG chains (Type C). Liposomes were prepared from egg phosphatidylcholine (ePC) and cholesterol (CH) (2:1, m/m) containing 6 mol{\%} of DSPE-PEG-COOH, and a monoclonal IgG antibody, 34A, which is highly specific to pulmonary endothelial cells, was conjugated to the carboxyl groups of DSPE-PEG-COOH to give various amounts of antibody molecules per liposome. Other immunoliposomes with PEG coating (Type B) or without PEG coating (an earlier type of immunoliposome, Type A) were prepared for comparison. The average molecular weight of PEG in Type B or C immunoliposomes was 2000. Type B and Type C liposomes without antibodies showed prolonged circulation time and reduced reticulo-endothelial system (RES) uptake owing to the presence of PEG. These three different types of 34A-immunoliposomes with 30-35 antibody molecules per vesicle were injected into mice to test the immunotargetability to the lung. The efficiency of lung binding of 34A-Type B was one-half of that of 34A-Type A, though a large amount of 34A-Type B remained in the blood circulation for a long time, suggesting that the steric hindrance of PEG chains reduced not only the immunospecific antibody-antigen binding, but also the RES uptake. The degree of lung binding of 34A-Type C was about 1.3-fold higher than that of 34A-Type A, indicating that recognition by the antibodies attached to the PEG terminal was not sterically hindered and that the free PEG (i.e., that not carrying antibody) was effective in increasing the blood concentration of immunoliposomes by enabling them to evade RES uptake. The latter phenomenon was confirmed by using nonspecific antibody-Type C immunoliposomes (14-Type C), which showed a high blood level for a long time. Our approach provides a simple means of conjugating antibodies directly to the distal end of PEG which is already bound to the liposome membrane, and should contribute to the development of superior targetable drug delivery vehicles for use in diagnostics and therapy.",
author = "Kazuo Maruyama and Tomoko Takizawa and Tsutomu Yuda and Stephen Kennel and Leaf Huang and Motoharu Iwatsuru",
year = "1995",
month = "3",
day = "8",
doi = "10.1016/0005-2736(94)00263-O",
language = "English (US)",
volume = "1234",
pages = "74--80",
journal = "Biochimica et Biophysica Acta - Biomembranes",
issn = "0005-2736",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Targetability of novel immunoliposomes modified with amphipathic poly(ethylene glycol) s conjugated at their distal terminals to monoclonal antibodies

AU - Maruyama, Kazuo

AU - Takizawa, Tomoko

AU - Yuda, Tsutomu

AU - Kennel, Stephen

AU - Huang, Leaf

AU - Iwatsuru, Motoharu

PY - 1995/3/8

Y1 - 1995/3/8

N2 - Distearoyl-N-(3-carboxypropionoyl poly(ethylene glycol) succinyl)phosphatidylethanolamine (DSPE-PEG-COOH) was newly synthesized and used to prepare novel immunoliposomes carrying monoclonal antibodies at the distal ends of the PEG chains (Type C). Liposomes were prepared from egg phosphatidylcholine (ePC) and cholesterol (CH) (2:1, m/m) containing 6 mol% of DSPE-PEG-COOH, and a monoclonal IgG antibody, 34A, which is highly specific to pulmonary endothelial cells, was conjugated to the carboxyl groups of DSPE-PEG-COOH to give various amounts of antibody molecules per liposome. Other immunoliposomes with PEG coating (Type B) or without PEG coating (an earlier type of immunoliposome, Type A) were prepared for comparison. The average molecular weight of PEG in Type B or C immunoliposomes was 2000. Type B and Type C liposomes without antibodies showed prolonged circulation time and reduced reticulo-endothelial system (RES) uptake owing to the presence of PEG. These three different types of 34A-immunoliposomes with 30-35 antibody molecules per vesicle were injected into mice to test the immunotargetability to the lung. The efficiency of lung binding of 34A-Type B was one-half of that of 34A-Type A, though a large amount of 34A-Type B remained in the blood circulation for a long time, suggesting that the steric hindrance of PEG chains reduced not only the immunospecific antibody-antigen binding, but also the RES uptake. The degree of lung binding of 34A-Type C was about 1.3-fold higher than that of 34A-Type A, indicating that recognition by the antibodies attached to the PEG terminal was not sterically hindered and that the free PEG (i.e., that not carrying antibody) was effective in increasing the blood concentration of immunoliposomes by enabling them to evade RES uptake. The latter phenomenon was confirmed by using nonspecific antibody-Type C immunoliposomes (14-Type C), which showed a high blood level for a long time. Our approach provides a simple means of conjugating antibodies directly to the distal end of PEG which is already bound to the liposome membrane, and should contribute to the development of superior targetable drug delivery vehicles for use in diagnostics and therapy.

AB - Distearoyl-N-(3-carboxypropionoyl poly(ethylene glycol) succinyl)phosphatidylethanolamine (DSPE-PEG-COOH) was newly synthesized and used to prepare novel immunoliposomes carrying monoclonal antibodies at the distal ends of the PEG chains (Type C). Liposomes were prepared from egg phosphatidylcholine (ePC) and cholesterol (CH) (2:1, m/m) containing 6 mol% of DSPE-PEG-COOH, and a monoclonal IgG antibody, 34A, which is highly specific to pulmonary endothelial cells, was conjugated to the carboxyl groups of DSPE-PEG-COOH to give various amounts of antibody molecules per liposome. Other immunoliposomes with PEG coating (Type B) or without PEG coating (an earlier type of immunoliposome, Type A) were prepared for comparison. The average molecular weight of PEG in Type B or C immunoliposomes was 2000. Type B and Type C liposomes without antibodies showed prolonged circulation time and reduced reticulo-endothelial system (RES) uptake owing to the presence of PEG. These three different types of 34A-immunoliposomes with 30-35 antibody molecules per vesicle were injected into mice to test the immunotargetability to the lung. The efficiency of lung binding of 34A-Type B was one-half of that of 34A-Type A, though a large amount of 34A-Type B remained in the blood circulation for a long time, suggesting that the steric hindrance of PEG chains reduced not only the immunospecific antibody-antigen binding, but also the RES uptake. The degree of lung binding of 34A-Type C was about 1.3-fold higher than that of 34A-Type A, indicating that recognition by the antibodies attached to the PEG terminal was not sterically hindered and that the free PEG (i.e., that not carrying antibody) was effective in increasing the blood concentration of immunoliposomes by enabling them to evade RES uptake. The latter phenomenon was confirmed by using nonspecific antibody-Type C immunoliposomes (14-Type C), which showed a high blood level for a long time. Our approach provides a simple means of conjugating antibodies directly to the distal end of PEG which is already bound to the liposome membrane, and should contribute to the development of superior targetable drug delivery vehicles for use in diagnostics and therapy.

UR - http://www.scopus.com/inward/record.url?scp=0028953974&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028953974&partnerID=8YFLogxK

U2 - 10.1016/0005-2736(94)00263-O

DO - 10.1016/0005-2736(94)00263-O

M3 - Article

VL - 1234

SP - 74

EP - 80

JO - Biochimica et Biophysica Acta - Biomembranes

JF - Biochimica et Biophysica Acta - Biomembranes

SN - 0005-2736

IS - 1

ER -