title: Inorganic phosphate-triggered release of anti-cancer arsenic trioxide from a self-delivery system: an in vitro and in vivo study.
abstract: On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced toxicity compared to the free drug. These results suggest a new drug delivery strategy which might be applied for ATO therapy on solid tumors.
authors.affiliation: College of Chemistry, Nanchang University, Nanchang, 330031, P. R. China.
authors.forename: Fei-yan
authors.initials: FY
authors.lastname: Chen
authors.affiliation: Institute for Advanced Study, Nanchang University, Nanchang, 330031, P. R. China. tangqun@ncu.edu.cn.
authors.forename: Jing-wei
authors.initials: JW
authors.lastname: Yi
authors.affiliation: Institute for Advanced Study, Nanchang University, Nanchang, 330031, P. R. China. tangqun@ncu.edu.cn.
authors.forename: Zhe-jia
authors.initials: ZJ
authors.lastname: Gu
authors.affiliation: Institute for Advanced Study, Nanchang University, Nanchang, 330031, P. R. China. tangqun@ncu.edu.cn.
authors.forename: Bin-bing
authors.initials: BB
authors.lastname: Tang
authors.affiliation: Jiangxi Academy of Medical Science, Nanchang University, Nanchang, 330031, P. R. China.
authors.forename: Jian-qi
authors.initials: JQ
authors.lastname: Li
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Padmakar
authors.initials: P
authors.lastname: Kulkarni
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Radiology, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Mason
authors.affiliation: Institute for Advanced Study, Nanchang University, Nanchang, 330031, P. R. China. tangqun@ncu.edu.cn and Department of Radiology, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Tang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000737:chemistry*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003911:Dextrans / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000473:pathology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010087:Oxides / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D003911:Dextrans; D010087:Oxides; D010710:Phosphates; D000077237:Arsenic Trioxide