Background: An improved light activated disinfection technique utilizing a specific photosensitizer formulation, liquid optical-conduit, oxygen-carrier and light energy of appropriate wavelength has been introduced recently. This study tested the efficacy of this improved light activated disinfection on ex vivo biofilms of Enterococcus faecalis at two different stages of maturation. Methods: Eighty-five tooth sections were prepared and endodontic biofilm of E. faecalis were grown within the root canal. In stage 1, conventional light activated disinfection (LAD), chemical disinfectant (sodium hypochlorite) and improved LAD were tested on four-day-old (immature) biofilms. In stage 2, conventional LAD, improved LAD and chemomechanical disinfection (alone and in combination with improved LAD) were tested on four-week-old (mature) biofilms. Results: Sodium hypochlorite and improved LAD showed the ability to significantly inactivate bacteria in four-day-old biofilms when compared to the control and LAD (p < 0.05). Inactivation of bacteria from deeper dentine was higher in improved LAD than sodium hypochlorite. In four-week-old biofilms, a combination of chemomechanical disinfection and improved LAD produced significant bacterial killing compared to either chemomechanical disinfection or improved LAD alone. Conclusions: This study highlighted the potential of improved LAD to kill bacteria within dentinal tubules. In combination with chemomechanical preparation, the improved LAD significantly inactivated four-week-old biofilm bacteria.

Pathogenic microorganisms pose a serious threat to global public health due to their persistent adaptation and growing resistance to antibiotics. Alternative therapeutic strategies are required to address this growing threat. Bactericidal antibiotics that are routinely prescribed to treat infections rely on hydroxyl radical formation for their therapeutic efficacies. We developed a redox approach to target bacteria using organotransition metal complexes to mediate the reduction of cellular O 2 to H 2 O 2 , as a precursor for hydroxyl radicals via Fenton reaction. We prepared a library of 480 unique organoruthenium Schiff-base complexes using a coordination-driven three-component assembly strategy and identified the lead organoruthenium complex Ru1 capable of selectively invoking oxidative stress in Gram-positive bacteria, in particular methicillin-resistant Staphylococcus aureus , via transfer hydrogenation reaction and/or single electron transfer on O 2 . This strategy paves the way for a targeted antimicrobial approach leveraging on the redox chemistry of organotransition metal complexes to combat drug resistance.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer,c haracterized by an aberrant metabolic phenotype with high metastatic capacity, resulting in poor patient prognoses and low survival rates.W e designed as eries of novel Au III cyclometalated prodrugs of energy-disrupting Type II antidiabetic drugs namely,m etformin and phenformin. Prodrug activation and release of the metformin ligand was achieved by tuning the cyclometalated Au III fragment. The lead complex 3met was 6000-fold more cytotoxic compared to uncoordinated metformin and significantly reduced tumor burden in mice with aggressive breast cancers with lymphocytic infiltration into tumor tissues.These effects was ascribed to 3met interfering with energy production in TNBCs and inhibiting associated pro-survival responses to induce deadly metabolic catastrophe.

A common challenge in Pt­(IV) prodrug design is the limited repertoire of linkers available to connect the Pt­(IV) scaffold with the bioactive payload. The commonly employed linkers are either too stable, leading to a linker artifact on the payload upon release, or too unstable, leading to premature release. In this study, we report the synthesis of a new class of Pt­(IV) prodrugs using masked self-immolative 4-aminobenzyl linkers for controlled and traceless codrug delivery. Upon reduction of self-immolative Pt­(IV) prodrugs, the detached axial ligands undergo decarboxylation and 1,6-elimination for payload release. Introduction of self-immolative linkers conferred good aqueous stability to the Pt­(IV) codrug complex. Investigation revealed that efficient 1,6-elimination could be attributed to stabilization of the p-aza-quinone-methide intermediate. In particular, the self-immolative Pt­(IV) prodrugs with cinnamate and coumarin derivatives were more potent than the coadministration of cisplatin with an unconjugated cinnamate or coumarin payload in vitro.

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