Medicinal
leads that are also compatible with imaging technologies
are attractive, as they facilitate the development of therapeutics
through direct mechanistic observations at the molecular level. In
this context, the uptake and antimicrobial activities of several luminescent
dinuclear RuII complexes against E. coli were assessed and compared to results obtained for another ESKAPE
pathogen, the Gram-positive major opportunistic pathogen Enterococcus
faecalis, V583. The most promising lead displays potent activity,
particularly against the Gram-negative bacteria, and potency is retained
in the uropathogenic multidrug resistant EC958 ST131 strain. Exploiting
the inherent luminescent properties of this complex, super-resolution
STED nanoscopy was used to image its initial localization at/in cellular
membranes and its subsequent transfer to the cell poles. Membrane
damage assays confirm that the complex disrupts the bacterial membrane
structure before internalization. Mammalian cell culture and animal
model studies indicate that the complex is not toxic to eukaryotes,
even at concentrations that are several orders of magnitude higher
than its minimum inhibitory concentration (MIC). Taken together, these
results have identified a lead molecular architecture for hard-to-treat,
multiresistant, Gram-negative bacteria, which displays activities
that are already comparable to optimized natural product-based leads.
Combining metallo-drugs with ionising radiation for synergistic cancer cell killing: chemical design principles, mechanisms of action and emerging applications.
Cancer treatment and therapy have made significant leaps and bounds in these past decades. However, there are still cases where surgical removal is impossible, metastases are challenging, and chemotherapy and radiotherapy pose severe side effects. Therefore, a need to find more effective and specific treatments still exists. One way is through the utilization of drug delivery agents (DDA) based on nanomaterials. In 2001, mesoporous silica nanoparticles (MSNs) were first used as DDA and have gained considerable attention in this field. The popularity of MSNs is due to their unique properties such as tunable particle and pore size, high surface area and pore volume, easy functionalization and surface modification, high stability and their capability to efficiently entrap cargo molecules. This review describes the latest advancement of MSNs as DDA for cancer treatment. We focus on the fabrication of MSNs, the challenges in DDA development and how MSNs address the problems through the development of smart DDA using MSNs. Besides that, MSNs have also been applied as a multifunctional DDA where they can serve in both the diagnostic and treatment of cancer. Overall, we argue MSNs provide a bright future for both the diagnosis and treatment of cancer.
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