Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells

Antonella Accardo, Rosalba Mansi, Giuseppina Salzano, Anna Morisco, Michela Aurilio, Antonio Parisi, Francesco Maione, Carla Cicala, Barbara Ziaco, Diego Tesauro, Luigi Aloj, Giuseppe De Rosa, Giancarlo Morelli

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose: This study addresses novel peptide modified liposomal doxorubicin to specifically target tissues overexpressing bombesin (BN) receptors. Methods: DOTA-(AEEA)2-peptides containing the [7-14]bombesin and the new BN-AA1 sequence have been synthesized to compare their binding properties and in serum stabilities. The amphiphilic peptide derivative (MonY-BN-AA1) containing BN-AA1, a hydrophobic moiety, polyethylenglycole (PEG), and diethylenetriaminepentaacetate (DTPA), has been synthesized. Liposomes have been obtained by mixing of MonY-BN-AA1 with 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC). Results: Both 111In labeled peptide derivatives present nanomolar Kd to PC-3 cells. 177Lu labeled peptide DOTA-(AEEA)2-BN-AA1 is very stable (half-life 414.1 h), while DOTA-(AEEA)2-BN, shows a half-life of 15.5 h. In vivo studies on the therapeutic efficacy of DSPC/MonY-BN-AA1/Dox in comparison to DSPC/MonY-BN/Dox, were performed in PC-3 xenograft bearing mice. Both formulations showed similar tumor growth inhibition (TGI) compared to control animals treated with non-targeted DSPC/Dox liposomes or saline solution. For DSPC/MonY-BN-AA1/Dox the maximum effect was observed 19 days after treatment. Conclusions: DSPC/MonY-BN-AA1/Dox nanovectors confirm the ability to selectively target and provide therapeutic efficacy in mice. The lack of receptor activation and possible acute biological side effects provided by using the AA1 antagonist bombesin sequence should provide safe working conditions for further development of this class of drug delivery vehicles.

Original languageEnglish
Pages (from-to)240-249
Number of pages10
JournalJournal of Drug Targeting
Volume21
Issue number3
DOIs
Publication statusPublished - Apr 2013

Fingerprint

Bombesin
Peptides
Neoplasms
Liposomes
Half-Life
liposomal doxorubicin
Bombesin Receptors
Heterografts
Sodium Chloride
1,2-distearoyllecithin
Therapeutics

Keywords

  • Animal studies
  • Anticancer efficacy
  • Bombesin peptide
  • Doxorubicin delivery
  • Liposomes for drug delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells. / Accardo, Antonella; Mansi, Rosalba; Salzano, Giuseppina; Morisco, Anna; Aurilio, Michela; Parisi, Antonio; Maione, Francesco; Cicala, Carla; Ziaco, Barbara; Tesauro, Diego; Aloj, Luigi; De Rosa, Giuseppe; Morelli, Giancarlo.

In: Journal of Drug Targeting, Vol. 21, No. 3, 04.2013, p. 240-249.

Research output: Contribution to journalArticle

Accardo, A, Mansi, R, Salzano, G, Morisco, A, Aurilio, M, Parisi, A, Maione, F, Cicala, C, Ziaco, B, Tesauro, D, Aloj, L, De Rosa, G & Morelli, G 2013, 'Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells', Journal of Drug Targeting, vol. 21, no. 3, pp. 240-249. https://doi.org/10.3109/1061186X.2012.741138
Accardo, Antonella ; Mansi, Rosalba ; Salzano, Giuseppina ; Morisco, Anna ; Aurilio, Michela ; Parisi, Antonio ; Maione, Francesco ; Cicala, Carla ; Ziaco, Barbara ; Tesauro, Diego ; Aloj, Luigi ; De Rosa, Giuseppe ; Morelli, Giancarlo. / Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells. In: Journal of Drug Targeting. 2013 ; Vol. 21, No. 3. pp. 240-249.
@article{20d12ed55b6f430da8c046895a7cd704,
title = "Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells",
abstract = "Purpose: This study addresses novel peptide modified liposomal doxorubicin to specifically target tissues overexpressing bombesin (BN) receptors. Methods: DOTA-(AEEA)2-peptides containing the [7-14]bombesin and the new BN-AA1 sequence have been synthesized to compare their binding properties and in serum stabilities. The amphiphilic peptide derivative (MonY-BN-AA1) containing BN-AA1, a hydrophobic moiety, polyethylenglycole (PEG), and diethylenetriaminepentaacetate (DTPA), has been synthesized. Liposomes have been obtained by mixing of MonY-BN-AA1 with 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC). Results: Both 111In labeled peptide derivatives present nanomolar Kd to PC-3 cells. 177Lu labeled peptide DOTA-(AEEA)2-BN-AA1 is very stable (half-life 414.1 h), while DOTA-(AEEA)2-BN, shows a half-life of 15.5 h. In vivo studies on the therapeutic efficacy of DSPC/MonY-BN-AA1/Dox in comparison to DSPC/MonY-BN/Dox, were performed in PC-3 xenograft bearing mice. Both formulations showed similar tumor growth inhibition (TGI) compared to control animals treated with non-targeted DSPC/Dox liposomes or saline solution. For DSPC/MonY-BN-AA1/Dox the maximum effect was observed 19 days after treatment. Conclusions: DSPC/MonY-BN-AA1/Dox nanovectors confirm the ability to selectively target and provide therapeutic efficacy in mice. The lack of receptor activation and possible acute biological side effects provided by using the AA1 antagonist bombesin sequence should provide safe working conditions for further development of this class of drug delivery vehicles.",
keywords = "Animal studies, Anticancer efficacy, Bombesin peptide, Doxorubicin delivery, Liposomes for drug delivery",
author = "Antonella Accardo and Rosalba Mansi and Giuseppina Salzano and Anna Morisco and Michela Aurilio and Antonio Parisi and Francesco Maione and Carla Cicala and Barbara Ziaco and Diego Tesauro and Luigi Aloj and {De Rosa}, Giuseppe and Giancarlo Morelli",
year = "2013",
month = "4",
doi = "10.3109/1061186X.2012.741138",
language = "English",
volume = "21",
pages = "240--249",
journal = "Journal of Drug Targeting",
issn = "1061-186X",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells

AU - Accardo, Antonella

AU - Mansi, Rosalba

AU - Salzano, Giuseppina

AU - Morisco, Anna

AU - Aurilio, Michela

AU - Parisi, Antonio

AU - Maione, Francesco

AU - Cicala, Carla

AU - Ziaco, Barbara

AU - Tesauro, Diego

AU - Aloj, Luigi

AU - De Rosa, Giuseppe

AU - Morelli, Giancarlo

PY - 2013/4

Y1 - 2013/4

N2 - Purpose: This study addresses novel peptide modified liposomal doxorubicin to specifically target tissues overexpressing bombesin (BN) receptors. Methods: DOTA-(AEEA)2-peptides containing the [7-14]bombesin and the new BN-AA1 sequence have been synthesized to compare their binding properties and in serum stabilities. The amphiphilic peptide derivative (MonY-BN-AA1) containing BN-AA1, a hydrophobic moiety, polyethylenglycole (PEG), and diethylenetriaminepentaacetate (DTPA), has been synthesized. Liposomes have been obtained by mixing of MonY-BN-AA1 with 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC). Results: Both 111In labeled peptide derivatives present nanomolar Kd to PC-3 cells. 177Lu labeled peptide DOTA-(AEEA)2-BN-AA1 is very stable (half-life 414.1 h), while DOTA-(AEEA)2-BN, shows a half-life of 15.5 h. In vivo studies on the therapeutic efficacy of DSPC/MonY-BN-AA1/Dox in comparison to DSPC/MonY-BN/Dox, were performed in PC-3 xenograft bearing mice. Both formulations showed similar tumor growth inhibition (TGI) compared to control animals treated with non-targeted DSPC/Dox liposomes or saline solution. For DSPC/MonY-BN-AA1/Dox the maximum effect was observed 19 days after treatment. Conclusions: DSPC/MonY-BN-AA1/Dox nanovectors confirm the ability to selectively target and provide therapeutic efficacy in mice. The lack of receptor activation and possible acute biological side effects provided by using the AA1 antagonist bombesin sequence should provide safe working conditions for further development of this class of drug delivery vehicles.

AB - Purpose: This study addresses novel peptide modified liposomal doxorubicin to specifically target tissues overexpressing bombesin (BN) receptors. Methods: DOTA-(AEEA)2-peptides containing the [7-14]bombesin and the new BN-AA1 sequence have been synthesized to compare their binding properties and in serum stabilities. The amphiphilic peptide derivative (MonY-BN-AA1) containing BN-AA1, a hydrophobic moiety, polyethylenglycole (PEG), and diethylenetriaminepentaacetate (DTPA), has been synthesized. Liposomes have been obtained by mixing of MonY-BN-AA1 with 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC). Results: Both 111In labeled peptide derivatives present nanomolar Kd to PC-3 cells. 177Lu labeled peptide DOTA-(AEEA)2-BN-AA1 is very stable (half-life 414.1 h), while DOTA-(AEEA)2-BN, shows a half-life of 15.5 h. In vivo studies on the therapeutic efficacy of DSPC/MonY-BN-AA1/Dox in comparison to DSPC/MonY-BN/Dox, were performed in PC-3 xenograft bearing mice. Both formulations showed similar tumor growth inhibition (TGI) compared to control animals treated with non-targeted DSPC/Dox liposomes or saline solution. For DSPC/MonY-BN-AA1/Dox the maximum effect was observed 19 days after treatment. Conclusions: DSPC/MonY-BN-AA1/Dox nanovectors confirm the ability to selectively target and provide therapeutic efficacy in mice. The lack of receptor activation and possible acute biological side effects provided by using the AA1 antagonist bombesin sequence should provide safe working conditions for further development of this class of drug delivery vehicles.

KW - Animal studies

KW - Anticancer efficacy

KW - Bombesin peptide

KW - Doxorubicin delivery

KW - Liposomes for drug delivery

UR - http://www.scopus.com/inward/record.url?scp=84875916349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875916349&partnerID=8YFLogxK

U2 - 10.3109/1061186X.2012.741138

DO - 10.3109/1061186X.2012.741138

M3 - Article

VL - 21

SP - 240

EP - 249

JO - Journal of Drug Targeting

JF - Journal of Drug Targeting

SN - 1061-186X

IS - 3

ER -