Bimetallic DNAsome Decorated with G4-DNA as a Nanozyme for Targeted and Enhanced Chemo/Chemodynamic Cancer Therapy.

Cancer is indisputably one of the major threats to mankind, and hence the design of new approaches for the improvement of existing therapeutic strategies is always wanted. Herein, the design of a tumor microenvironment-responsive, DNA-based chemodynamic therapy (CDT) nanoagent with dual Fenton reaction centers for targeted cancer therapy is reported. Self-assembly of DNA amphiphile containing copper complex as the hydrophobic Fenton reaction center results in the formation of CDT-active DNAsome with Cu2+-based Fenton catalytic site as the hydrophobic core and hydrophilic ssDNA protrude on the surface. DNA-based surface addressability of the DNAsome is then used for the integration of second Fenton reaction center, which is a peroxidase-mimicking DNAzyme noncovalently loaded with Hemin and Doxorubicin, via DNA hybridization to give a CDT agent having dual Fenton reaction centers. Targeted internalization of the CDT nanoagent and selective generation of •OH inside HeLa cell are also shown. Excellent therapeutic efficiency is observed for the CDT nanoagent both in vitro and in vivo, and the enhanced efficacy is attributed to the combined and synergetic action of CDT and chemotherapy.

Multifunctional siRNA/ferrocene/cyclodextrin nanoparticles for enhanced chemodynamic cancer therapy.

The therapeutic outcome of chemodynamic therapy (CDT) is greatly hindered by the presence of oxidative damage repair proteins (MTH1) inside cancer cells. These oxidative damage repair proteins detoxify the action of radicals generated by Fenton or Fenton-like reactions. Hence, it is extremely important to develop a simple strategy for the downregulation of MTH1 protein inside cancer cells along with the delivery of metal ions into cancer cells. A one-pot host-guest supramolecular approach for the codelivery of MTH1 siRNA and metal ions into a cancer cell is reported. Our approach involves the fabrication of an inclusion complex between cationic ß-cyclodextrin and a ferrocene prodrug, which spontaneously undergoes amphiphilicity-driven self-assembly to form spherical nanoparticles (NPs) having a positively charged surface. The cationic surface of the NPs was then explored for the loading of MTH1 siRNA through electrostatic interactions. Using HeLa cells as a representative example, efficient uptake of the NPs, delivery of MTH1 siRNA and the enhanced CDT of the nanoformulation are demonstrated. This work highlights the potential of the supramolecular approach as a simple yet efficient method for the delivery of siRNA across the cell membrane for enhanced chemodynamic therapy.

Effects of combined cataract surgery and trabeculectomy with mitomycin C on ocular dimensions.

AIMS: To characterise changes in ocular dimensions after combined cataract operation and trabeculectomy with mitomycin C using separate incisions (combined operation). METHODS: 24 consecutive eyes that had combined operation and 16 eyes that had cataract operation alone were enrolled. The axial lengths before and after operations were determined with non-contact optical coherence biometry. The intraocular pressures (IOP), axial lengths, corneal curvatures, and the expected and observed refractive errors before and after operations were compared. RESULTS: After a combined operation, mean IOP was significantly reduced from 16.6 (SD 5.8) mm Hg to 10.9 (4.1) mm Hg (p<0.00001), and mean axial length was significantly shortened from 24.10 (0.98) mm to 23.98 (0.96) mm (p<0.00001). The mean axial length reduction after combined operation (117 (57) microm) was significantly larger than the reduction after cataract operation alone (75 (38) microm, p<0.02), and correlated significantly with the postoperative IOP (p<0.002). There was a mean with the rule surgically induced corneal astigmatism of 0.44 (0.83) dioptre by vector analysis, and a significant increase of mean keratometry reading of 0.23 (0.46) dioptre after a combined operation. However, there was no significant difference between the expected and observed refractive errors. CONCLUSIONS: Despite an alteration of the axial length and corneal curvature, the refractive outcome after a combined operation did not differ significantly from the predicted refraction.