Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent
Antonella Accardo1,2*, Giuseppina Salsano3*, Anna Morisco4, Michela Aurilio4, Antonio Parisi5, Francesco Maione5, Carla Cicala5, Diego Tesauro1,2, Luigi Aloj4, Giuseppe De Rosa3, Giancarlo Morelli1,21CIRPeB, Department of Biological Sciences and IBB CNR, University of Naples “Federico...
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Dove Medical Press
2012
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oai:doaj.org-article:88b361968d8c42989c5331bb1b9dde172021-12-02T07:28:37ZPeptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent1176-91141178-2013https://doaj.org/article/88b361968d8c42989c5331bb1b9dde172012-04-01T00:00:00Zhttp://www.dovepress.com/peptide-modified-liposomes-for-selective-targeting-of-bombesin-recepto-a9705https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Antonella Accardo1,2*, Giuseppina Salsano3*, Anna Morisco4, Michela Aurilio4, Antonio Parisi5, Francesco Maione5, Carla Cicala5, Diego Tesauro1,2, Luigi Aloj4, Giuseppe De Rosa3, Giancarlo Morelli1,21CIRPeB, Department of Biological Sciences and IBB CNR, University of Naples “Federico II”, 2Invectors srl, 3Department of Pharmaceutical Chemistry, University of Naples “Federico II”, 4Department of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, 5Department of Experimental Pharmacology, University of Naples “Federico II”, Napoli, Italy*These authors contributed equally to this workObjectives: 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.Keywords: bombesin peptide, doxorubicin delivery, gastrin-releasing peptide receptors, PC-3 cells, theranostic applicationsAccardo ASalsano GMorisco AAurilio MParisi AMaione FCicala CTesauro DAloj LDe Rosa GMorelli GDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 2007-2017 (2012) |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 Accardo A Salsano G Morisco A Aurilio M Parisi A Maione F Cicala C Tesauro D Aloj L De Rosa G Morelli G Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent |
| description |
Antonella Accardo1,2*, Giuseppina Salsano3*, Anna Morisco4, Michela Aurilio4, Antonio Parisi5, Francesco Maione5, Carla Cicala5, Diego Tesauro1,2, Luigi Aloj4, Giuseppe De Rosa3, Giancarlo Morelli1,21CIRPeB, Department of Biological Sciences and IBB CNR, University of Naples “Federico II”, 2Invectors srl, 3Department of Pharmaceutical Chemistry, University of Naples “Federico II”, 4Department of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, 5Department of Experimental Pharmacology, University of Naples “Federico II”, Napoli, Italy*These authors contributed equally to this workObjectives: 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.Keywords: bombesin peptide, doxorubicin delivery, gastrin-releasing peptide receptors, PC-3 cells, theranostic applications |
| format |
article |
| author |
Accardo A Salsano G Morisco A Aurilio M Parisi A Maione F Cicala C Tesauro D Aloj L De Rosa G Morelli G |
| author_facet |
Accardo A Salsano G Morisco A Aurilio M Parisi A Maione F Cicala C Tesauro D Aloj L De Rosa G Morelli G |
| author_sort |
Accardo A |
| title |
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_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_sort |
peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent |
| publisher |
Dove Medical Press |
| publishDate |
2012 |
| url |
https://doaj.org/article/88b361968d8c42989c5331bb1b9dde17 |
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