Drug Delivery and Translational Research

, Volume 9, Issue 1, pp 215–226 | Cite as

Easy formulation of liposomal doxorubicin modified with a bombesin peptide analogue for selective targeting of GRP receptors overexpressed by cancer cells

  • Antonella Accardo
  • Silvia Mannucci
  • Elena Nicolato
  • Federica Vurro
  • Carlo Diaferia
  • Pietro Bontempi
  • Pasquina MarzolaEmail author
  • Giancarlo MorelliEmail author
Original Article


The article concerns the obtainment of liposomal doxorubicin (Dox) in which liposomes are externally modified with a targeting peptide able to drive the formulation in a selective way on membrane receptors overexpressed in tumors. We developed a kit composed by three different vials: (A) a vial containing a sterile, translucent, red dispersion of the liposomal doxorubicin drug (Doxil®), (B) a vial filled with a lyophilized powder of a modified phospholipid with a reactive function (DSPE-Peg-maleimide), and (C) a vial containing a 1–9 bombesin peptide analogue (Cys-BN-AA1) chemically modified to react in stoichiometric ratio respect to DSPE-Peg-maleimide. The chosen peptide is a stable analogue antagonist of the wild-type 1–9 bombesin peptide; it is very stable in serum; maintains high specificity, with nanomolar affinity, towards gastrin release peptide receptors (GRPRs indicated also as BB2); and is overexpressed in some cancer cells. Results on animal studies clearly indicate that in mice treated with the kit product (i.e., pegylated liposomal Dox modified with the bombesin analogue, Doxil-BN-AA1), tumor growth is reduced, with an improved efficacy respect to mice treated with non-modified pegylated liposomal Dox or with saline solution.


Bombesin peptide Liposomes Doxorubicin delivery Anticancer efficacy Formulation kit 


Funding information

This research was funded by Italian Ministry for Research (M.I.U.R.), 0016/09 593/2000 (Invectors) and FIRB “RINAME” RBAP114AMK projects.

Compliance with ethical standards

Conflict of interest

A. Accardo and G. Morelli participate in a spin-off company (Invectors, srl) devoted to the development of targeted liposomal compounds for cancer therapy. The other authors report no conflicts of interest in this work.


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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  • Antonella Accardo
    • 1
    • 2
  • Silvia Mannucci
    • 3
  • Elena Nicolato
    • 3
  • Federica Vurro
    • 3
  • Carlo Diaferia
    • 1
  • Pietro Bontempi
    • 4
  • Pasquina Marzola
    • 4
    Email author
  • Giancarlo Morelli
    • 1
    • 2
    Email author
  1. 1.Department of Pharmacy and Interuniversity Research Centre on Bioactive Peptides (CIRPeB), IBB CNRUniversity of Naples “Federico II”NaplesItaly
  2. 2.Invectors srlNaplesItaly
  3. 3.Department of Neurological Biomedical and Movement SciencesUniversity of VeronaVeronaItaly
  4. 4.Department of Computer ScienceUniversity of VeronaVeronaItaly

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