title: Biocatalytic release of an anticancer drug from nucleic-acids-capped mesoporous SiO2 Using DNA or molecular biomarkers as triggering stimuli.
abstract: DNA-gated mesoporous SiO2 nanoparticles, MP-SiO2 NPs, loaded with rhodamine B, RhB, act as "smart" materials that reveal complementary "sense" and "release" functionalities. The unlocking of the DNA pore-capping units is achieved by the biocatalytic cleavage of the DNA, and the unlocking process is amplified by the regeneration of the analyte-trigger. The RhB-loaded MP-SiO2 NPs are capped with nucleic acid hairpin structures that lock the RhB in the pores. Opening of the hairpin structures by a nucleic acid analyte trigger or by the formation of an aptamer-substrate (ATP) complex leads to the formation of duplex structures being cleaved by exonuclease III, Exo III, or the nicking enzyme, Nb. BbvCI. This results in the regeneration of the target analytes, the autonomous unlocking of the pores, and the release of RhB. The systems reveal selectivity, and one-, two-, three-base mutations in the target DNA, or substitution of ATP with other triphosphate nucleotides, prohibit the unlocking of the pores. In analogy to the biocatalytic release of the model fluorophore substrates, the anticancer drug camptothecin, CPT, was entrapped in the pores and locked by the 1 or 11 hairpin structures. The drug was released from the pores in the presence of the nucleic acid 2 or ATP and the Exo III, as biocatalyst. Similarly, CPT locked in the pores by the 6 or 12 hairpins were released from the pores in the presence of ATP and Nb. BbvCI, as nicking enzyme, respectively. The effects of the CPT-loaded MP-SiO2 NPs, capped with the ATP-dependent lock 6, on the viability of MDA-231 breast cancer cells and MCF-10a normal breast cells were examined. We find that after 48 h, 65% cell death was observed for the MDA-231 cancer cells, where only 25% cell death was observed for the normal cells. The higher cell death of the cancer cells correlates well with the enhanced metabolic synthesis of ATP in the cancerous cells.
authors.affiliation: Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Zhanxia
authors.initials: Z
authors.lastname: Zhang
authors.forename: Dora
authors.initials: D
authors.lastname: Balogh
authors.forename: Fuan
authors.initials: F
authors.lastname: Wang
authors.forename: Sohn Yang
authors.initials: SY
authors.lastname: Sung
authors.forename: Rachel
authors.initials: R
authors.lastname: Nechushtai
authors.forename: Itamar
authors.initials: I
authors.lastname: Willner
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001483:Base Sequence; D055162:Biocatalysis; D015415:Biomarkers / Q000737:chemistry*; D001943:Breast Neoplasms / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage* / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D017931:DNA Primers; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D009696:Nucleic Acids / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D017931:DNA Primers; D005456:Fluorescent Dyes; D009696:Nucleic Acids; D012235:Rhodamines; D012822:Silicon Dioxide; D004247:DNA; C029773:rhodamine B; D002166:Camptothecin