New self-assembly nanoparticles and stealth liposomes for the delivery of zoledronic acid: A comparative study

Monica Marra, Giuseppina Salzano, Carlo Leonetti, Manuela Porru, Renato Franco, Silvia Zappavigna, Giuseppina Liguori, Gerardo Botti, Paolo Chieffi, Monica Lamberti, Giovanni Vitale, Alberto Abbruzzese, Maria Immacolata La Rotonda, Giuseppe De Rosa, Michele Caraglia

Research output: Contribution to journalArticlepeer-review

Abstract

Zoledronic acid (ZOL) is a drug whose potent anti-cancer activity is limited by its short plasma half-life and rapid uptake and accumulation within bone. We have recently proposed new delivery systems to avoid ZOL accumulation into the bone, thus improving extra-skeletal bioavailability. In this work, we have compared the technological and anti-cancer features of either ZOL-containing self-assembly PEGylated nanoparticles (NPs) or ZOL-encapsulating PEGylated liposomes (LIPO-ZOL). ZOL-containing NPs showed superior technological characteristics in terms of mean diameter, size distribution, and ZOL encapsulation efficiency, compared to LIPO-ZOL. Moreover, the anti-cancer activity of NPs in nude mice xenografted with prostate cancer PC3 cells was higher than that one induced by LIPO-ZOL. In addition, NPs induced the complete remission of tumour xenografts and an increase of survival time higher than that one observed with LIPO-ZOL. It has also to be considered that PC3 tumour xenografts were almost completely resistant to the anti-cancer effects induced by free ZOL. Both nanotechnological products did not induce toxic effects not affecting the mice weight nor inducing deaths. Moreover, the histological examination of some vital organs such as liver, kidney and spleen did not find any changes in terms of necrotic effects or modifications in the inflammatory infiltrate. On the other hand, NPs but not LIPO-ZOL caused a statistically significant reduction of the tumour associated macrophages (TAM) in tumour xenografts. This effect was paralleled by a significant increase of both necrotic and apoptotic indexes. The effects of the NPs were also higher in terms of neo-angiogenesis inhibition. These results suggest the future preclinical development of ZOL-encapsulating NPs in the treatment of human cancer.

Original languageEnglish
Pages (from-to)302-309
Number of pages8
JournalBiotechnology Advances
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Calcium phosphate nanoparticles
  • Liposomes
  • Nanotechnology
  • Necrosis
  • Neo-angiogenesis
  • Prostate adenocarcinoma
  • Self-assembly nanoparticles
  • Signal transduction pathways
  • Tumour-associated macrophages
  • Zoledronic acid

ASJC Scopus subject areas

  • Biotechnology

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