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Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent

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 tar...

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Autores principales: Accardo, Antonella, Salsano, Giuseppina, Morisco, Anna, Aurilio, Michela, Parisi, Antonio, Maione, Francesco, Cicala, Carla, Tesauro, Diego, Aloj, Luigi, De Rosa, Giuseppe, Morelli, Giancarlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356180/
https://www.ncbi.nlm.nih.gov/pubmed/22619538
http://dx.doi.org/10.2147/IJN.S29242
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author Accardo, Antonella
Salsano, Giuseppina
Morisco, Anna
Aurilio, Michela
Parisi, Antonio
Maione, Francesco
Cicala, Carla
Tesauro, Diego
Aloj, Luigi
De Rosa, Giuseppe
Morelli, Giancarlo
author_facet Accardo, Antonella
Salsano, Giuseppina
Morisco, Anna
Aurilio, Michela
Parisi, Antonio
Maione, Francesco
Cicala, Carla
Tesauro, Diego
Aloj, Luigi
De Rosa, Giuseppe
Morelli, Giancarlo
author_sort Accardo, Antonella
collection PubMed
description 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 C(18) 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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spelling pubmed-33561802012-05-22 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 Int J Nanomedicine Original Research 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 C(18) 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. Dove Medical Press 2012 2012-04-17 /pmc/articles/PMC3356180/ /pubmed/22619538 http://dx.doi.org/10.2147/IJN.S29242 Text en © 2012 Accardo et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
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
title Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent
title_full Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent
title_fullStr Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent
title_full_unstemmed Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent
title_short Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent
title_sort peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356180/
https://www.ncbi.nlm.nih.gov/pubmed/22619538
http://dx.doi.org/10.2147/IJN.S29242
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