Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells

A potential theranostic agent

Antonella Accardo, Giuseppina Salsano, Anna Morisco, Michela Aurilio, Antonio Parisi, Francesco Maione, Carla Cicala, Diego Tesauro, Luigi Aloj, Giuseppe De Rosa, Giancarlo Morelli

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Objectives: Drug delivery systems consisting of liposomes displaying a cell surface receptor-targeting peptide are being developed to specifically deliver chemotherapeutic drugs to tumors overexpressing a target receptor. This study addresses novel liposome composition approaches to specifically target tissues overexpressing bombesin (BN) receptors. Methods: A new amphiphilic peptide derivative (MonY-BN) containing the BN(7-14) peptide, the DTPA (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two C18 alkyl chains, and polyethylene glycol spacers, has been synthesized by solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN with 1,2-distearoyl-sn-glycero- 3-phosphocholine (DSPC). The structural and biological properties of these new target-selective drug-delivery systems have been characterized. Results: Liposomes with a DSPC/MonY-BN (97/3 molar ratio) composition showed a diameter of 145.5±31.5 nm and a polydispersity index of 0.20 ± 0.05. High doxorubicin (Dox) loading was obtained with the remote pH gradient method using citrate as the inner buffer. Specific binding to PC-3 cells of DSPC/MonY-BN liposomes was obtained (2.7% ± 0.3%, at 37°C), compared with peptide-free DSPC liposomes (1.4% ± 0.2% at 37°C). Incubation of cells with DSPC/ MonY-BN/Dox showed significantly lower cell survival compared with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft-bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour growth inhibition (60%) compared with nonspecific DSPC/ Dox liposomes (36%) relative to control animals. Conclusion: The structural and loading properties of DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are encouraging for further development of this approach for target-specific cancer chemotherapy.

Original languageEnglish
Pages (from-to)2007-2017
Number of pages11
JournalInternational Journal of Nanomedicine
Volume7
DOIs
Publication statusPublished - 2012

Fingerprint

Bombesin Receptors
Phosphorylcholine
Liposomes
Bombesin
Peptides
Cells
Doxorubicin
Neoplasms
Drug Delivery Systems
Tumors
Bearings (structural)
Proton-Motive Force
Chemotherapy
Gradient methods
Theranostic Nanomedicine
Cell Surface Receptors
Polydispersity
Cytotoxicity
Chelating Agents
Chelation

Keywords

  • Bombesin peptide
  • Doxorubicin delivery
  • Gastrin-releasing peptide receptors
  • PC-3 cells
  • Theranostic applications

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Organic Chemistry
  • Drug Discovery

Cite this

Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells : A potential theranostic agent. / Accardo, Antonella; Salsano, Giuseppina; Morisco, Anna; Aurilio, Michela; Parisi, Antonio; Maione, Francesco; Cicala, Carla; Tesauro, Diego; Aloj, Luigi; De Rosa, Giuseppe; Morelli, Giancarlo.

In: International Journal of Nanomedicine, Vol. 7, 2012, p. 2007-2017.

Research output: Contribution to journalArticle

Accardo, Antonella ; Salsano, Giuseppina ; Morisco, Anna ; Aurilio, Michela ; Parisi, Antonio ; Maione, Francesco ; Cicala, Carla ; Tesauro, Diego ; Aloj, Luigi ; De Rosa, Giuseppe ; Morelli, Giancarlo. / Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells : A potential theranostic agent. In: International Journal of Nanomedicine. 2012 ; Vol. 7. pp. 2007-2017.
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abstract = "Objectives: Drug delivery systems consisting of liposomes displaying a cell surface receptor-targeting peptide are being developed to specifically deliver chemotherapeutic drugs to tumors overexpressing a target receptor. This study addresses novel liposome composition approaches to specifically target tissues overexpressing bombesin (BN) receptors. Methods: A new amphiphilic peptide derivative (MonY-BN) containing the BN(7-14) peptide, the DTPA (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two C18 alkyl chains, and polyethylene glycol spacers, has been synthesized by solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN with 1,2-distearoyl-sn-glycero- 3-phosphocholine (DSPC). The structural and biological properties of these new target-selective drug-delivery systems have been characterized. Results: Liposomes with a DSPC/MonY-BN (97/3 molar ratio) composition showed a diameter of 145.5±31.5 nm and a polydispersity index of 0.20 ± 0.05. High doxorubicin (Dox) loading was obtained with the remote pH gradient method using citrate as the inner buffer. Specific binding to PC-3 cells of DSPC/MonY-BN liposomes was obtained (2.7{\%} ± 0.3{\%}, at 37°C), compared with peptide-free DSPC liposomes (1.4{\%} ± 0.2{\%} at 37°C). Incubation of cells with DSPC/ MonY-BN/Dox showed significantly lower cell survival compared with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft-bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour growth inhibition (60{\%}) compared with nonspecific DSPC/ Dox liposomes (36{\%}) relative to control animals. Conclusion: The structural and loading properties of DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are encouraging for further development of this approach for target-specific cancer chemotherapy.",
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T2 - A potential theranostic agent

AU - Accardo, Antonella

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AU - Morisco, Anna

AU - Aurilio, Michela

AU - Parisi, Antonio

AU - Maione, Francesco

AU - Cicala, Carla

AU - Tesauro, Diego

AU - Aloj, Luigi

AU - De Rosa, Giuseppe

AU - Morelli, Giancarlo

PY - 2012

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N2 - Objectives: Drug delivery systems consisting of liposomes displaying a cell surface receptor-targeting peptide are being developed to specifically deliver chemotherapeutic drugs to tumors overexpressing a target receptor. This study addresses novel liposome composition approaches to specifically target tissues overexpressing bombesin (BN) receptors. Methods: A new amphiphilic peptide derivative (MonY-BN) containing the BN(7-14) peptide, the DTPA (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two C18 alkyl chains, and polyethylene glycol spacers, has been synthesized by solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN with 1,2-distearoyl-sn-glycero- 3-phosphocholine (DSPC). The structural and biological properties of these new target-selective drug-delivery systems have been characterized. Results: Liposomes with a DSPC/MonY-BN (97/3 molar ratio) composition showed a diameter of 145.5±31.5 nm and a polydispersity index of 0.20 ± 0.05. High doxorubicin (Dox) loading was obtained with the remote pH gradient method using citrate as the inner buffer. Specific binding to PC-3 cells of DSPC/MonY-BN liposomes was obtained (2.7% ± 0.3%, at 37°C), compared with peptide-free DSPC liposomes (1.4% ± 0.2% at 37°C). Incubation of cells with DSPC/ MonY-BN/Dox showed significantly lower cell survival compared with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft-bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour growth inhibition (60%) compared with nonspecific DSPC/ Dox liposomes (36%) relative to control animals. Conclusion: The structural and loading properties of DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are encouraging for further development of this approach for target-specific cancer chemotherapy.

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