title: Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CIRPeB, Department of Biological Sciences and IBB CNR, University of Naples Federico II, Napoli, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Accardo
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Salsano
authors.forename: Anna
authors.initials: A
authors.lastname: Morisco
authors.forename: Michela
authors.initials: M
authors.lastname: Aurilio
authors.forename: Antonio
authors.initials: A
authors.lastname: Parisi
authors.forename: Francesco
authors.initials: F
authors.lastname: Maione
authors.forename: Carla
authors.initials: C
authors.lastname: Cicala
authors.forename: Diego
authors.initials: D
authors.lastname: Tesauro
authors.forename: Luigi
authors.initials: L
authors.lastname: Aloj
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Rosa
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Morelli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001839:Bombesin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050997:Nanomedicine; D004369:Pentetic Acid / Q000737:chemistry; D010446:Peptide Fragments / Q000008:administration & dosage*; D010713:Phosphatidylcholines / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D018004:Receptors, Bombesin; D013501:Surface-Active Agents; C118536:bombesin (7-14); D004369:Pentetic Acid; D004317:Doxorubicin; C010942:1,2-distearoyllecithin; D001839:Bombesin