Single-cell and bulk ICP-MS investigation of accumulation patterns of Pt-based metallodrugs in cisplatin-sensitive and -resistant cell models.

In research enabling preclinical development and attaining a deeper understanding of the behavior of metallodrugs in cancer cells with acquired resistance, intracellular Pt accumulation could be considered an important biomarker and analytical focus. In this work, Pt accumulation patterns in terms of the number of cells and Pt mass in single cells were precisely defined by using inductively coupled plasma-mass spectrometry (ICP-MS) operating in a fast time-resolved analysis mode. This technique is otherwise known as single-cell (SC)-ICP-MS.

Investigations on detoxification mechanisms of novel para-phenylenediamine analogues through N-acetyltransferase 1 (NAT-1).

Para-phenylenediamine (PPD) is one of the most used chemicals in oxidative hair dyes. However, its use has been associated with adverse effects on health, including contact dermatitis and other systemic toxicities. Novel PPD derivatives have been proposed as a safer replacement for PPD.

Targeted Antibacterial Strategy Based on Reactive Oxygen Species Generated from Dioxygen Reduction Using an Organoruthenium Complex.

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.

Interfering with Metabolic Profile of Triple-Negative Breast Cancers Using Rationally Designed Metformin Prodrugs.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by an aberrant metabolic phenotype with high metastatic capacity, resulting in poor patient prognoses and low survival rates. We designed a series of novel Au cyclometalated prodrugs of energy-disrupting Type II antidiabetic drugs namely, metformin and phenformin. Prodrug activation and release of the metformin ligand was achieved by tuning the cyclometalated Au fragment.

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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.