title: Nanotechnologies to use bisphosphonates as potent anticancer agents: the effects of zoledronic acid encapsulated into liposomes.
abstract: Zoledronic acid (ZOL) is a potent amino-bisphosphonate used for the treatment of bone metastases with recently reported antitumor activity. However, the short plasma half-life and rapid accumulation in bone limits the use of ZOL as an antitumor agent in extraskeletal tissues. Therefore, we developed stealth liposomes encapsulating ZOL (LipoZOL) to increase extraskeletal drug availability. Compared to free ZOL, LipoZOL induced a stronger inhibition of growth of a range of different cancer cell lines in vitro. LipoZOL also caused significantly larger inhibition of tumor growth and increased the overall survival in murine models of human prostate cancer and multiple myeloma, in comparison with ZOL. Moreover, a strong inhibition of vasculogenetic events without evidence of necrosis in the tumor xenografts from prostate cancer was recorded after treatment with LipoZOL. We demonstrated both antitumor activity and tolerability of LipoZOL in preclinical animal models of both solid and hematopoietic malignancies, providing a rationale for early exploration of use of LipoZOL as a potential anticancer agent in cancer patients.
  
  
  BACKGROUND
  The short plasma half-life and rapid accumulation in bone limits the use of zoledronic acid as an antitumor agent in extraskeletal tissues. Therefore, stealth liposomes encapsulating ZOL (LipoZOL) have been developed to increase extraskeletal drug availability.
authors: Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy.
authors: Monica
authors: M
authors: Marra
authors: Giuseppina
authors: G
authors: Salzano
authors: Carlo
authors: C
authors: Leonetti
authors: Pierfrancesco
authors: P
authors: Tassone
authors: Marco
authors: M
authors: Scarsella
authors: Silvia
authors: S
authors: Zappavigna
authors: Teresa
authors: T
authors: Calimeri
authors: Renato
authors: R
authors: Franco
authors: Giuseppina
authors: G
authors: Liguori
authors: Giovanni
authors: G
authors: Cigliana
authors: Roberta
authors: R
authors: Ascani
authors: Maria Immacolata
authors: MI
authors: La Rotonda
authors: Alberto
authors: A
authors: Abbruzzese
authors: Pierosandro
authors: P
authors: Tagliaferri
authors: Michele
authors: M
authors: Caraglia
authors: Giuseppe
authors: G
authors: De Rosa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008081:Liposomes / Q000737:chemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D008081:Liposomes; D000077211:Zoledronic Acid