title: Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells.
abstract: OBJECTIVE
  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
  Both111In 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.
authors.affiliation: a CIRPeB, Department of Biological Sciences & IBB CNR, University of Naples "Federico II" , Napoli, Italy.|b Invectors srl , Napoli, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Accardo
authors.affiliation: c Division of Radiological Chemistry, University Hospital Basel , Basel, Switzerland.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Mansi
authors.affiliation: d Department of Pharmaceutical and Toxicological Chemistry, University of Naples "Federico II" , Napoli, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Salzano
authors.affiliation: e Department of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori , Fondazione "G. Pascale", Napoli, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Morisco
authors.affiliation: e Department of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori , Fondazione "G. Pascale", Napoli, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Aurilio
authors.affiliation: f Department of Experimental Pharmacology, University of Naples "Federico II" , Napoli, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Parisi
authors.affiliation: f Department of Experimental Pharmacology, University of Naples "Federico II" , Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Maione
authors.affiliation: f Department of Experimental Pharmacology, University of Naples "Federico II" , Napoli, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Cicala
authors.affiliation: b Invectors srl , Napoli, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ziaco
authors.affiliation: a CIRPeB, Department of Biological Sciences & IBB CNR, University of Naples "Federico II" , Napoli, Italy.|b Invectors srl , Napoli, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Tesauro
authors.affiliation: e Department of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori , Fondazione "G. Pascale", Napoli, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Aloj
authors.affiliation: d Department of Pharmaceutical and Toxicological Chemistry, University of Naples "Federico II" , Napoli, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Rosa
authors.affiliation: a CIRPeB, Department of Biological Sciences & IBB CNR, University of Naples "Federico II" , Napoli, Italy.|b Invectors srl , Napoli, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Morelli