Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells(410 views) 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
Journal Of Drug Targeting (ISSN: 1061-186x), 2012 Nov 21; 21(3): 240-249.
Keywords: Animal Studies, Anticancer Efficacy, Bombesin Peptide, Doxorubicin Delivery, Liposomes For Drug Delivery, Amino Acid Derivative, Amphophile, Bombesin Antagonist, Bombesin Receptor, Indium 111, Lutetium 177, Macrogol, Pentetic Acid, Peptide Derivative, Tetraxetan, Amino Acid Sequence, Animal Experiment, Animal Model, Article, Binding Affinity, Binding Assay, Binding Site, Cancer Cell, Cancer Inhibition, Cell Survival, Cell Viability, Controlled Study, Cytotoxicity, Drug Delivery System, Drug Efficacy, Drug Selectivity, Drug Stability, Drug Targeting, Female, High Performance Liquid Chromatography, Human, Human Tissue, Hydrophobicity, In Vitro Study, In Vivo Study, Incubation Temperature, Isotope Labeling, Mouse, Nonhuman, Peptide Synthesis, Priority Journal, Prostate Cancer, Receptor Affinity, Tumor Growth, Tumor Volume, Tumor Xenograft, Weight Reduction, Zeta Potential,
Affiliations: *** IBB - CNR ***
CIRPeB, Department of Biological Sciences, University of Naples Federico II, Napoli, Italy
Invectors Srl, Napoli, Italy
Division of Radiological Chemistry, University Hospital Basel, Basel, Switzerland
Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Napoli, Italy
Department of Nuclear Medicine, Istituto Nazionale per Lo Studio e la Cura Dei Tumori, Fondazione G. Pascale, Napoli, Italy
Department of Experimental Pharmacology, University of Naples Federico II, Napoli, Italy
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Nagalla, S. R., Barry, B. J., Creswick, K. C., Eden, P., Taylor, J. T., Spindel, E. R., Cloning of a receptor for amphibian [Phe13] bombesin distinct from the receptor for gastrin-releasing peptide: Identification of a fourth bombesin receptor subtype (BB4) (1995) Proc Natl Acad Sci USA, 92, pp. 6205-6209
Parry, J. J., Kelly, T. S., Andrews, R., Rogers, B. E., In vitro and in vivo evaluation of 64Cu-labeled DOTA-linker-bombesin (7- 14) analogues containing different amino acid linker moieties (2007) Bioconjug Chem, 18, pp. 1110-1117
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Zhu, Y. F., Chen, C., Recent advances in small molecule gonadotrophin-releasing hormone receptor antagonists (2004) Expert Opin Ther Pat, 14, pp. 187-199
Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells
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 In-111 labeled peptide derivatives present nanomolar Kd to PC-3 cells. Lu-177 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.
Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells
No results.
Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells