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Nanoscale Coordination Polymers for Platinum-Based Anticancer Drug Delivery

2008; American Chemical Society; Volume: 130; Issue: 35 Linguagem: Inglês

10.1021/ja803383k

1943-2984

William J. Rieter, Kimberly M. Pott, K. Taylor-Pashow, Wenbin Lin,

Nanoparticle-Based 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.