Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells.

We describe herein a Toll-like receptor 3 (TLR3) targeting delivery system based on mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic-polycytidylic acid (poly(I:C)) for controlled cargo delivery in SK-BR-3 breast carcinoma cells. Our results show that poly(I:C)-conjugated nanoparticles efficiently targeted breast cancer cells due to dsRNA-TLR3 interaction. Such interaction also triggered apoptotic pathways in SK-BR-3, significantly decreasing cells viability. Poly(I:C) cytotoxic effect in breast carcinoma cells was enhanced by loading nanoparticles' mesopores with the anthracyclinic antibiotic doxorubicin, a commonly used chemotherapeutic agent.

Experimental and theoretical studies on the mechanism of photochemical hydrogen transfer from 2-aminobenzimidazole to nπ* and ππ* aromatic ketones.

This work has examined the photoreactivity of benzophenone (3), 2-benzoylthiophene (4), 4-methoxybenzophenone (5), 4,4'-dimethoxybenzophenone (6), and 4-carboxybenzophenone (7) with 2-aminobenzimidazole (1). Laser flash photolysis (LFP) revealed quenching of the aromatic ketone triplets by 1, leading to formation of ketyl radicals plus aminyl radical 1-H•. The quenching rate constants obtained for 3 (nπ* triplet) and 4 (ππ* triplet) were 6.2 × 10(9) and 3.9 × 10(9) M(-1) s(-1), respectively. The similarity between the two values suggests that the process is not a pure hydrogen abstraction but rather a charge transfer followed by proton transfer. This is in agreement with thermodynamic calculations, using the Rehm-Weller equation. In the case of 5 and 6, the transient absorption spectra showed distinct bands corresponding to both types of triplets (nπ* and ππ*); their ratio was found to depend on solvent polarity. In the presence of 1, spectral changes were also consistent with formation of the aminyl/ketyl radical pairs. The rate constants for quenching of both types of triplets were very high, in the range 10(9)-10(10) M(-1) s(-1). When an electron acceptor substituent was attached to the aromatic ring, as in 7 (nπ* triplet), the quenching rate constant was higher (8 × 10(9) M(-1) s(-1)), close to diffusion control. The reaction mechanism for hydrogen abstraction from 1 by triplet excited 3 or 4 was theoretically studied using density functional theory (DFT) methods. The results suggest formation of ground state molecular complexes, where one electron is transferred from the 2-aminobenzimidazole to the benzophenone or benzoylthiophene moieties upon excitation, giving radical ion pairs; subsequent proton transfer from the amino group to the carbonyl oxygen atoms leads to the neutral biradicals. A comparison between the relative energies and geometries of the species involved in the photochemical reactions indicates that all ketones follow a similar mechanism.

Experimental and theoretical (DFT) characterization of the excited states and N-centered radical species derived from 2-aminobenzimidazole, the core substructure of a family of bioactive compounds.

Fluorescence spectroscopy, laser flash photolysis (LFP), and density functional theory (DFT) calculations have been performed to understand the photobehavior of 2-aminobenzimidazole (1). The emission lifetime and quantum yield are solvent-dependent. Direct LFP of 1 at 266 nm in MeCN solution results in the generation of a transient identified as radical 1(-H)(*) by comparison with the species generated upon tert-butyl peroxide (ROOR) irradiation in the presence of 1. In addition, a transient assigned as the triplet state is detected in MeOH solution. Theoretical DFT studies on the hydrogen abstraction process support formation of a 1...OR complex, which undergoes nitrogen to oxygen hydrogen transfer, producing the above-mentioned 1(-H)(*) radicals.