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
SN - 0734-9750
VL - 30
SP - 302
EP - 309
JO - Biotechnology Advances
JF - Biotechnology Advances
IS - 1
ER -