Publication

Targeting 15d-prostaglandin J(2) to hepatic stellate cells: Two options evaluated

Hagens, W. I., Mattos Pinto, A., Greupink, R., de Jager-Krikken, A., Reker-Smit, C., van Loenen - Weemaes, A., Gouw, A. S. H., Poelstra, K. & Beljaars, L., Mar-2007, In : Pharmaceutical Research. 24, 3, p. 566-574 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Hagens, W. I., Mattos Pinto, A., Greupink, R., de Jager-Krikken, A., Reker-Smit, C., van Loenen - Weemaes, A., ... Beljaars, L. (2007). Targeting 15d-prostaglandin J(2) to hepatic stellate cells: Two options evaluated. Pharmaceutical Research, 24(3), 566-574. https://doi.org/10.1007/s11095-006-9175-2

Author

Hagens, Werner I. ; Mattos Pinto, Adriana ; Greupink, Rick ; de Jager-Krikken, Alie ; Reker-Smit, Catharina ; van Loenen - Weemaes, Anne-miek ; Gouw, Annette S. H. ; Poelstra, Klaas ; Beljaars, Leonie. / Targeting 15d-prostaglandin J(2) to hepatic stellate cells : Two options evaluated. In: Pharmaceutical Research. 2007 ; Vol. 24, No. 3. pp. 566-574.

Harvard

Hagens, WI, Mattos Pinto, A, Greupink, R, de Jager-Krikken, A, Reker-Smit, C, van Loenen - Weemaes, A, Gouw, ASH, Poelstra, K & Beljaars, L 2007, 'Targeting 15d-prostaglandin J(2) to hepatic stellate cells: Two options evaluated', Pharmaceutical Research, vol. 24, no. 3, pp. 566-574. https://doi.org/10.1007/s11095-006-9175-2

Standard

Targeting 15d-prostaglandin J(2) to hepatic stellate cells : Two options evaluated. / Hagens, Werner I.; Mattos Pinto, Adriana; Greupink, Rick; de Jager-Krikken, Alie; Reker-Smit, Catharina; van Loenen - Weemaes, Anne-miek; Gouw, Annette S. H.; Poelstra, Klaas; Beljaars, Leonie.

In: Pharmaceutical Research, Vol. 24, No. 3, 03.2007, p. 566-574.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Hagens WI, Mattos Pinto A, Greupink R, de Jager-Krikken A, Reker-Smit C, van Loenen - Weemaes A et al. Targeting 15d-prostaglandin J(2) to hepatic stellate cells: Two options evaluated. Pharmaceutical Research. 2007 Mar;24(3):566-574. https://doi.org/10.1007/s11095-006-9175-2


BibTeX

@article{534f52ef5c5e465abf52f1e2e6b535d3,
title = "Targeting 15d-prostaglandin J(2) to hepatic stellate cells: Two options evaluated",
abstract = "Purpose: Delivery of apoptosis-inducing compounds to hepatic stellate cells (HSC) may be an effective strategy to reverse liver fibrosis. The aim of this study was therefore to examine the selective targeting of the apoptosis-inducing drug 15-deoxy-triangle 12,14-prostaglandin J(2) (15dPGJ(2)) with two different HSC-carriers: human serum albumin modified with the sugar mannose-6-phosphate (M6PHSA) or albumin modified with PDGF-receptor recognizing peptides (pPBHSA).Methods and Results: After chemical conjugation of 15dPGJ(2) to the carriers, the constructs displayed pharmacological activity and specific receptor-mediated binding to HSC in vitro. Unlike 15dPGJ(2)-pPBHSA, the cellular binding of 15dPGJ(2)-M6PHSA was reduced by a scavenger receptor antagonist. In vivo, both conjugates rapidly accumulated in fibrotic livers. Intrahepatic analysis revealed that 15dPGJ(2)-M6PHSA mainly accumulated in HSC, and to a lesser extent in Kupffer cells. 15dPGJ(2)-pPBHSA also predominantly accumulated in HSC with additional uptake in hepatocytes. Assessment of target receptors in human cirrhotic livers revealed that M6P/IGFII-receptor expression was present in fibrotic areas. PDGF-beta receptor expression was abundantly expressed on human fibroblasts.Conclusions: These studies show that 15dPGJ(2) coupled to either M6PHSA or pPBHSA is specifically taken up by HSC and is highly effective within these cells. Both carriers differ with respect to receptor specificity, leading to differences in intrahepatic distribution. Nevertheless, both carriers can be used to deliver the apoptosis-inducing drug 15dPGJ(2) to HSC in vivo.",
keywords = "antifibrotic drugs, drug targeting, hepatic stellate cells, liver fibrosis, 15dPGJ2, FACTOR-II RECEPTOR, PROLIFERATOR-ACTIVATED RECEPTORS, MANNOSE 6-PHOSPHATE RECEPTOR, GROWTH-FACTOR RECEPTOR, MONOCLONAL-ANTIBODIES, SELECTIVE DELIVERY, MYCOPHENOLIC-ACID, RAT, ALBUMIN, EXPRESSION",
author = "Hagens, {Werner I.} and {Mattos Pinto}, Adriana and Rick Greupink and {de Jager-Krikken}, Alie and Catharina Reker-Smit and {van Loenen - Weemaes}, Anne-miek and Gouw, {Annette S. H.} and Klaas Poelstra and Leonie Beljaars",
year = "2007",
month = "3",
doi = "10.1007/s11095-006-9175-2",
language = "English",
volume = "24",
pages = "566--574",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "SPRINGER/PLENUM PUBLISHERS",
number = "3",

}

RIS

TY - JOUR

T1 - Targeting 15d-prostaglandin J(2) to hepatic stellate cells

T2 - Two options evaluated

AU - Hagens, Werner I.

AU - Mattos Pinto, Adriana

AU - Greupink, Rick

AU - de Jager-Krikken, Alie

AU - Reker-Smit, Catharina

AU - van Loenen - Weemaes, Anne-miek

AU - Gouw, Annette S. H.

AU - Poelstra, Klaas

AU - Beljaars, Leonie

PY - 2007/3

Y1 - 2007/3

N2 - Purpose: Delivery of apoptosis-inducing compounds to hepatic stellate cells (HSC) may be an effective strategy to reverse liver fibrosis. The aim of this study was therefore to examine the selective targeting of the apoptosis-inducing drug 15-deoxy-triangle 12,14-prostaglandin J(2) (15dPGJ(2)) with two different HSC-carriers: human serum albumin modified with the sugar mannose-6-phosphate (M6PHSA) or albumin modified with PDGF-receptor recognizing peptides (pPBHSA).Methods and Results: After chemical conjugation of 15dPGJ(2) to the carriers, the constructs displayed pharmacological activity and specific receptor-mediated binding to HSC in vitro. Unlike 15dPGJ(2)-pPBHSA, the cellular binding of 15dPGJ(2)-M6PHSA was reduced by a scavenger receptor antagonist. In vivo, both conjugates rapidly accumulated in fibrotic livers. Intrahepatic analysis revealed that 15dPGJ(2)-M6PHSA mainly accumulated in HSC, and to a lesser extent in Kupffer cells. 15dPGJ(2)-pPBHSA also predominantly accumulated in HSC with additional uptake in hepatocytes. Assessment of target receptors in human cirrhotic livers revealed that M6P/IGFII-receptor expression was present in fibrotic areas. PDGF-beta receptor expression was abundantly expressed on human fibroblasts.Conclusions: These studies show that 15dPGJ(2) coupled to either M6PHSA or pPBHSA is specifically taken up by HSC and is highly effective within these cells. Both carriers differ with respect to receptor specificity, leading to differences in intrahepatic distribution. Nevertheless, both carriers can be used to deliver the apoptosis-inducing drug 15dPGJ(2) to HSC in vivo.

AB - Purpose: Delivery of apoptosis-inducing compounds to hepatic stellate cells (HSC) may be an effective strategy to reverse liver fibrosis. The aim of this study was therefore to examine the selective targeting of the apoptosis-inducing drug 15-deoxy-triangle 12,14-prostaglandin J(2) (15dPGJ(2)) with two different HSC-carriers: human serum albumin modified with the sugar mannose-6-phosphate (M6PHSA) or albumin modified with PDGF-receptor recognizing peptides (pPBHSA).Methods and Results: After chemical conjugation of 15dPGJ(2) to the carriers, the constructs displayed pharmacological activity and specific receptor-mediated binding to HSC in vitro. Unlike 15dPGJ(2)-pPBHSA, the cellular binding of 15dPGJ(2)-M6PHSA was reduced by a scavenger receptor antagonist. In vivo, both conjugates rapidly accumulated in fibrotic livers. Intrahepatic analysis revealed that 15dPGJ(2)-M6PHSA mainly accumulated in HSC, and to a lesser extent in Kupffer cells. 15dPGJ(2)-pPBHSA also predominantly accumulated in HSC with additional uptake in hepatocytes. Assessment of target receptors in human cirrhotic livers revealed that M6P/IGFII-receptor expression was present in fibrotic areas. PDGF-beta receptor expression was abundantly expressed on human fibroblasts.Conclusions: These studies show that 15dPGJ(2) coupled to either M6PHSA or pPBHSA is specifically taken up by HSC and is highly effective within these cells. Both carriers differ with respect to receptor specificity, leading to differences in intrahepatic distribution. Nevertheless, both carriers can be used to deliver the apoptosis-inducing drug 15dPGJ(2) to HSC in vivo.

KW - antifibrotic drugs

KW - drug targeting

KW - hepatic stellate cells

KW - liver fibrosis

KW - 15dPGJ2

KW - FACTOR-II RECEPTOR

KW - PROLIFERATOR-ACTIVATED RECEPTORS

KW - MANNOSE 6-PHOSPHATE RECEPTOR

KW - GROWTH-FACTOR RECEPTOR

KW - MONOCLONAL-ANTIBODIES

KW - SELECTIVE DELIVERY

KW - MYCOPHENOLIC-ACID

KW - RAT

KW - ALBUMIN

KW - EXPRESSION

U2 - 10.1007/s11095-006-9175-2

DO - 10.1007/s11095-006-9175-2

M3 - Article

VL - 24

SP - 566

EP - 574

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 3

ER -

ID: 4529027