Prussian blue nanoparticles as nanocargoes for delivering DNA drugs to cancer cells.

We studied the use of Prussian blue nanoparticles (PBNPs) as novel nanocarriers for sending DNA drugs into cancer cells. 11-mercaptoundecanoic acid (MUA) was used to functionalize the surfaces of PBNPs (nanocubes with an average dimension of 75 nm) for subsequent covalent grafting of a 33-mer DNA drug with a FAM reporter at the 3' end. The PBNPs synthesis and DNA drug conjugation were characterized by transmission electron microscopy (TEM) and Fourier-transform infrared absorption (FTIR), respectively. The drug was a decoy oligodeoxynucleotide (dODN) that inhibits the signal transducer and activator of transcription 3 (STAT3). The DNA-PBNPs drug (dODN@MUA-PBNPs) was delivered into human prostate carcinoma 22rv1 cells by endocytosis in vitro as confirmed by confocal fluorescence microscopy. MTT cell viability assays were carried out to assess the effect of the DNA-PBNPs drug. The results showed that the dODN molecules were successfully conjugated to the MUA modified PBNPs via amide and/or disulfide bond formation and could thus be successfully delivered into the cancer cells. The control experiments showed that the unconjugated dODN molecules were not able to enter the cancer cells no matter whether non-functionalized PBNPs were present or not. It was also found that the DNA-PBNPs drugs were internalized and then distributed homogeneously throughout the cell, including cytoplasmic and nucleic regions, after endocytosis. The cancer cell-killing ability increased with the amount of dODN conjugated on PBNPs and the dosage of DNA-PBNPs drug internalized.