Nanoparticles loaded with nutlin-3 display cytotoxicity towards p53 wildtype JVM-2 but not towards p53mutated bjab leukemic cells

R. Voltan, P. Secchiero, B. Ruozi, L. Caruso, F. Forni, M. Palomba, G. Zauli, M. A. Vandelli

Research output: Contribution to journalArticlepeer-review


The small molecule Nutlin-3 is a potent antagonist of the murine double minute 2 (MDM2)/p53 interaction exhibiting promising therapeutic anti-cancer activity. Nutlin-3 has been proposed as an anti-neoplastic agent for the treatment of onco-hematological diseases characterized by a lower incidence of p53 mutation with respect to solid tumors. Indeed, based on its selective non-genotoxic p53 activation, Nutlin-3 might represent an alternative to the current cytotoxic chemotherapy. To overcome the poor bioavailability of Nutlin-3, we have assessed the potential efficacy of Nutlin-3 loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NP) against hematological malignancies. To test the specificity of the anti-leukemic activity, we have used leukemic cell lines characterized by different p53 status (JVM-2 and BJAB). NP loaded with Nutlin-3 (NP-Nutlin) were rapidly taken up by the leukemic cells and were as effective as native Nutlin-3 in promoting both induction of apoptosis and cell cycle arrest in p53wild-type JVM-2 cells, but not in p53 mutated BJAB cells. Moreover, injection of NP-Nutlin, but not of free Nutlin-3, in a JVM-2-derived xenograft mouse model, reduced the subcutaneous tumor volume and promoted induction of apoptosis in the tumor mass. Overall, the chemical and structural characteristics of the NP-Nutlin-3, as well as their biological activity in vitro and in vivo, made them promising for further preclinical evaluations as potentially useful anti-leukemic carriers.

Original languageEnglish
Pages (from-to)2712-2722
Number of pages11
JournalCurrent Medicinal Chemistry
Issue number21
Publication statusPublished - Jul 2013


  • Apoptosis
  • B-cell leukemia
  • Cell cycle
  • Nutlin-3
  • P53
  • PLGA nanoparticles

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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