LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer

Natalia V. Nukolova, Hardeep S. Oberoi, Yi Zhao, Vladimir P. Chekhonin, Alexander V. Kabanov, Tatiana K Bronich

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Targeted drug delivery using multifunctional polymeric nanocarriers is a modern approach for cancer therapy. Our purpose was to prepare targeted nanogels for selective delivery of chemotherapeutic agent cisplatin to luteinizing hormone-releasing hormone (LHRH) receptor overexpressing tumor in vivo. Building blocks of such delivery systems consisted of innovative soft block copolymer nanogels with ionic cores serving as a reservoir for cisplatin (loading 35%) and a synthetic analogue of LHRH conjugated to the nanogels via poly(ethylene glycol) spacer. Covalent attachment of (D-Lys6)-LHRH to nanogels was shown to be possible without loss in either the ligand binding affinity or the nanogel drug incorporation ability. LHRH-nanogel accumulation was specific to the LHRH-receptor positive A2780 ovarian cancer cells and not toward LHRH-receptor negative SKOV-3 cells. The LHRH-nanogel cisplatin formulation was more effective and less toxic than equimolar doses of free cisplatin or untargeted nanogels in the treatment of receptor-positive ovarian cancer xenografts in mice. Collectively, the study indicates that LHRH mediated nanogel-cisplatin delivery is a promising formulation strategy for therapy of tumors that express the LHRH receptor.

Original languageEnglish (US)
Pages (from-to)3913-3921
Number of pages9
JournalMolecular Pharmaceutics
Volume10
Issue number10
DOIs
StatePublished - Oct 7 2013

Fingerprint

Gonadotropin-Releasing Hormone
Ovarian Neoplasms
Cisplatin
LHRH Receptors
NanoGel
Neoplasms
Ethylene Glycol
Poisons
Heterografts
Pharmaceutical Preparations
Ligands
Therapeutics

Keywords

  • Cisplatin
  • LHRH-targeting
  • Nanogels
  • Ovarian cancer
  • Targeted drug delivery

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Nukolova, N. V., Oberoi, H. S., Zhao, Y., Chekhonin, V. P., Kabanov, A. V., & Bronich, T. K. (2013). LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer. Molecular Pharmaceutics, 10(10), 3913-3921. https://doi.org/10.1021/mp4003688

LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer. / Nukolova, Natalia V.; Oberoi, Hardeep S.; Zhao, Yi; Chekhonin, Vladimir P.; Kabanov, Alexander V.; Bronich, Tatiana K.

In: Molecular Pharmaceutics, Vol. 10, No. 10, 07.10.2013, p. 3913-3921.

Research output: Contribution to journalArticle

Nukolova, NV, Oberoi, HS, Zhao, Y, Chekhonin, VP, Kabanov, AV & Bronich, TK 2013, 'LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer', Molecular Pharmaceutics, vol. 10, no. 10, pp. 3913-3921. https://doi.org/10.1021/mp4003688
Nukolova, Natalia V. ; Oberoi, Hardeep S. ; Zhao, Yi ; Chekhonin, Vladimir P. ; Kabanov, Alexander V. ; Bronich, Tatiana K. / LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer. In: Molecular Pharmaceutics. 2013 ; Vol. 10, No. 10. pp. 3913-3921.
@article{dca468eca2aa45159d598397717c96a3,
title = "LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer",
abstract = "Targeted drug delivery using multifunctional polymeric nanocarriers is a modern approach for cancer therapy. Our purpose was to prepare targeted nanogels for selective delivery of chemotherapeutic agent cisplatin to luteinizing hormone-releasing hormone (LHRH) receptor overexpressing tumor in vivo. Building blocks of such delivery systems consisted of innovative soft block copolymer nanogels with ionic cores serving as a reservoir for cisplatin (loading 35{\%}) and a synthetic analogue of LHRH conjugated to the nanogels via poly(ethylene glycol) spacer. Covalent attachment of (D-Lys6)-LHRH to nanogels was shown to be possible without loss in either the ligand binding affinity or the nanogel drug incorporation ability. LHRH-nanogel accumulation was specific to the LHRH-receptor positive A2780 ovarian cancer cells and not toward LHRH-receptor negative SKOV-3 cells. The LHRH-nanogel cisplatin formulation was more effective and less toxic than equimolar doses of free cisplatin or untargeted nanogels in the treatment of receptor-positive ovarian cancer xenografts in mice. Collectively, the study indicates that LHRH mediated nanogel-cisplatin delivery is a promising formulation strategy for therapy of tumors that express the LHRH receptor.",
keywords = "Cisplatin, LHRH-targeting, Nanogels, Ovarian cancer, Targeted drug delivery",
author = "Nukolova, {Natalia V.} and Oberoi, {Hardeep S.} and Yi Zhao and Chekhonin, {Vladimir P.} and Kabanov, {Alexander V.} and Bronich, {Tatiana K}",
year = "2013",
month = "10",
day = "7",
doi = "10.1021/mp4003688",
language = "English (US)",
volume = "10",
pages = "3913--3921",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "10",

}

TY - JOUR

T1 - LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer

AU - Nukolova, Natalia V.

AU - Oberoi, Hardeep S.

AU - Zhao, Yi

AU - Chekhonin, Vladimir P.

AU - Kabanov, Alexander V.

AU - Bronich, Tatiana K

PY - 2013/10/7

Y1 - 2013/10/7

N2 - Targeted drug delivery using multifunctional polymeric nanocarriers is a modern approach for cancer therapy. Our purpose was to prepare targeted nanogels for selective delivery of chemotherapeutic agent cisplatin to luteinizing hormone-releasing hormone (LHRH) receptor overexpressing tumor in vivo. Building blocks of such delivery systems consisted of innovative soft block copolymer nanogels with ionic cores serving as a reservoir for cisplatin (loading 35%) and a synthetic analogue of LHRH conjugated to the nanogels via poly(ethylene glycol) spacer. Covalent attachment of (D-Lys6)-LHRH to nanogels was shown to be possible without loss in either the ligand binding affinity or the nanogel drug incorporation ability. LHRH-nanogel accumulation was specific to the LHRH-receptor positive A2780 ovarian cancer cells and not toward LHRH-receptor negative SKOV-3 cells. The LHRH-nanogel cisplatin formulation was more effective and less toxic than equimolar doses of free cisplatin or untargeted nanogels in the treatment of receptor-positive ovarian cancer xenografts in mice. Collectively, the study indicates that LHRH mediated nanogel-cisplatin delivery is a promising formulation strategy for therapy of tumors that express the LHRH receptor.

AB - Targeted drug delivery using multifunctional polymeric nanocarriers is a modern approach for cancer therapy. Our purpose was to prepare targeted nanogels for selective delivery of chemotherapeutic agent cisplatin to luteinizing hormone-releasing hormone (LHRH) receptor overexpressing tumor in vivo. Building blocks of such delivery systems consisted of innovative soft block copolymer nanogels with ionic cores serving as a reservoir for cisplatin (loading 35%) and a synthetic analogue of LHRH conjugated to the nanogels via poly(ethylene glycol) spacer. Covalent attachment of (D-Lys6)-LHRH to nanogels was shown to be possible without loss in either the ligand binding affinity or the nanogel drug incorporation ability. LHRH-nanogel accumulation was specific to the LHRH-receptor positive A2780 ovarian cancer cells and not toward LHRH-receptor negative SKOV-3 cells. The LHRH-nanogel cisplatin formulation was more effective and less toxic than equimolar doses of free cisplatin or untargeted nanogels in the treatment of receptor-positive ovarian cancer xenografts in mice. Collectively, the study indicates that LHRH mediated nanogel-cisplatin delivery is a promising formulation strategy for therapy of tumors that express the LHRH receptor.

KW - Cisplatin

KW - LHRH-targeting

KW - Nanogels

KW - Ovarian cancer

KW - Targeted drug delivery

UR - http://www.scopus.com/inward/record.url?scp=84888205008&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888205008&partnerID=8YFLogxK

U2 - 10.1021/mp4003688

DO - 10.1021/mp4003688

M3 - Article

C2 - 23957812

AN - SCOPUS:84888205008

VL - 10

SP - 3913

EP - 3921

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 10

ER -