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 journalArticle

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

Fingerprint

zoledronic acid
Liposomes
Nanoparticles
Self assembly
Acids
Neoplasms
Tumors
Heterografts
Bone

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

Cite this

New self-assembly nanoparticles and stealth liposomes for the delivery of zoledronic acid : A comparative study. / Marra, Monica; Salzano, Giuseppina; Leonetti, Carlo; Porru, Manuela; Franco, Renato; Zappavigna, Silvia; Liguori, Giuseppina; Botti, Gerardo; Chieffi, Paolo; Lamberti, Monica; Vitale, Giovanni; Abbruzzese, Alberto; La Rotonda, Maria Immacolata; De Rosa, Giuseppe; Caraglia, Michele.

In: Biotechnology Advances, Vol. 30, No. 1, 01.2012, p. 302-309.

Research output: Contribution to journalArticle

Marra, M, Salzano, G, Leonetti, C, Porru, M, Franco, R, Zappavigna, S, Liguori, G, Botti, G, Chieffi, P, Lamberti, M, Vitale, G, Abbruzzese, A, La Rotonda, MI, De Rosa, G & Caraglia, M 2012, 'New self-assembly nanoparticles and stealth liposomes for the delivery of zoledronic acid: A comparative study', Biotechnology Advances, vol. 30, no. 1, pp. 302-309. https://doi.org/10.1016/j.biotechadv.2011.06.018
Marra, Monica ; Salzano, Giuseppina ; Leonetti, Carlo ; Porru, Manuela ; Franco, Renato ; Zappavigna, Silvia ; Liguori, Giuseppina ; Botti, Gerardo ; Chieffi, Paolo ; Lamberti, Monica ; Vitale, Giovanni ; Abbruzzese, Alberto ; La Rotonda, Maria Immacolata ; De Rosa, Giuseppe ; Caraglia, Michele. / New self-assembly nanoparticles and stealth liposomes for the delivery of zoledronic acid : A comparative study. In: Biotechnology Advances. 2012 ; Vol. 30, No. 1. pp. 302-309.
@article{068946cd1ec04d278eface023fc5676c,
title = "New self-assembly nanoparticles and stealth liposomes for the delivery of zoledronic acid: A comparative study",
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.",
keywords = "Calcium phosphate nanoparticles, Liposomes, Nanotechnology, Necrosis, Neo-angiogenesis, Prostate adenocarcinoma, Self-assembly nanoparticles, Signal transduction pathways, Tumour-associated macrophages, Zoledronic acid",
author = "Monica Marra and Giuseppina Salzano and Carlo Leonetti and Manuela Porru and Renato Franco and Silvia Zappavigna and Giuseppina Liguori and Gerardo Botti and Paolo Chieffi and Monica Lamberti and Giovanni Vitale and Alberto Abbruzzese and {La Rotonda}, {Maria Immacolata} and {De Rosa}, Giuseppe and Michele Caraglia",
year = "2012",
month = "1",
doi = "10.1016/j.biotechadv.2011.06.018",
language = "English",
volume = "30",
pages = "302--309",
journal = "Biotechnology Advances",
issn = "0734-9750",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - New self-assembly nanoparticles and stealth liposomes for the delivery of zoledronic acid

T2 - A comparative study

AU - Marra, Monica

AU - Salzano, Giuseppina

AU - Leonetti, Carlo

AU - Porru, Manuela

AU - Franco, Renato

AU - Zappavigna, Silvia

AU - Liguori, Giuseppina

AU - Botti, Gerardo

AU - Chieffi, Paolo

AU - Lamberti, Monica

AU - Vitale, Giovanni

AU - Abbruzzese, Alberto

AU - La Rotonda, Maria Immacolata

AU - De Rosa, Giuseppe

AU - Caraglia, Michele

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

KW - Calcium phosphate nanoparticles

KW - Liposomes

KW - Nanotechnology

KW - Necrosis

KW - Neo-angiogenesis

KW - Prostate adenocarcinoma

KW - Self-assembly nanoparticles

KW - Signal transduction pathways

KW - Tumour-associated macrophages

KW - Zoledronic acid

UR - http://www.scopus.com/inward/record.url?scp=84855725118&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855725118&partnerID=8YFLogxK

U2 - 10.1016/j.biotechadv.2011.06.018

DO - 10.1016/j.biotechadv.2011.06.018

M3 - Article

C2 - 21741464

AN - SCOPUS:84855725118

VL - 30

SP - 302

EP - 309

JO - Biotechnology Advances

JF - Biotechnology Advances

SN - 0734-9750

IS - 1

ER -