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.
Subject(s)
Antineoplastic Agents/administration & dosage , Biomarkers/chemistry , Camptothecin/administration & dosage , DNA/chemistry , Nucleic Acids/chemistry , Silicon Dioxide/chemistry , Antineoplastic Agents/chemistry , Base Sequence , Biocatalysis , Breast Neoplasms/pathology , Camptothecin/chemistry , DNA Primers , Female , Fluorescent Dyes/chemistry , Humans , Rhodamines/chemistry , Spectrometry, FluorescenceABSTRACT
The photonic- and redox-triggered cyclic uptake and release of organic substrates in functionalized mesoporous SiO2 nanoparticles (NPs) is demonstrated. The mesoporous SiO2 NPs are functionalized with nitrospiropyran photoisomerizable units. Rhodamine B is encapsulated in the channels of the SiO2 NPs and trapped by the hydrophobic nitrospiropyran capping units. Photoisomerization of the capping units to the protonated nitromerocyanine groups opens the channels and releases the encapsulated dye. Similarly, modification of the SiO2 channels by chloronaphthoquinone units traps eosin Y in the channels, by means of donor-acceptor interactions. The reduction of the quinone units to the chloronaphth hydroquinone donor groups opens the channels and releases the encapsulated substrate. The novelty of the study rests on the demonstration of the reversible and cyclic photostimulated or redox-activated uptake and release of substrates from the mesoporous SiO2 NPs.
