Nanoscale coordination polymers for platinum-based anticancer drug delivery.
Pt-containing nanoscale coordination polymer (NCP) particles with the formula of Tb2(DSCP)3(H2O)12 (where DSCP represents disuccinatocisplatin), NCP-1, were precipitated from an aqueous solution of Tb3+ ions and DSCP bridging ligands via the addition of a poor solvent. SEM and TEM images showed that as-synthesized NCP-1 exhibited a spherical morphology with a DLS diameter of 58.3 +/- 11.3 nm. NCP-1 particles were stabilized against rapid dissolution in water by encapsulation in shells of amorphous silica. The resulting silica-coated particles NCP-1' exhibited significantly longer half-lives for DSCP release from the particles (a t1/2 of 9 h for NCP-1' with 7 nm silica coating vs t1/2 of 1 h for as-synthesized NCP-1). In vitro cancer cell cytotoxicity assays with the human colon carcinoma cell line (HT-29) showed that internalized NCP-1' particles readily released the DSCP moieties which were presumably reduced to cytotoxic Pt(II) species to give the Pt-containing NCPs anticancer efficacy superior to the cisplatin standard. The generality of this degradable nanoparticle formulation should allow for the design of NCPs as effective delivery vehicles for a variety of biologically and medically important cargoes such as therapeutic and imaging agents.
Rieter
William J
WJ
Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Pott
Kimberly M
KM
Taylor
Kathryn M L
KM
Lin
Wenbin
W
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002945:Cisplatin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D019073:HT29 Cells; D006801:Humans; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry*; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry; D013725:Terbium / Q000737:chemistry; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D013725:Terbium; D012822:Silicon Dioxide; C067490:terbium chloride; D002945:Cisplatin