Doble synergetic anticancer activity through a combined chemo-photodynamic therapy and bioimaging of a novel Cas-ZnONPs all-in-one system.

A strategy for cancer treatment was implemented, based on chemo-photodynamic therapy, utilizing a novel formulation, low-cost system called Cas-ZnONPs. This system consisted of the incorporation of Casiopeina III-ia (CasIII-ia), a hydrophilic copper coordination compound with well-documented anti-neoplastic activity, on Zinc oxide nanoparticles (ZnONPs) with apoptotic activity and lipophilicity, allowing them to permeate biological barriers. Additionally, ZnONPs exhibited fluorescence, with emission at different wavelengths depending on their agglomeration and enabling real-time tracking biodistribution. Also, ZnONPs served as a sensitizer, generating reactive oxygen species (ROS) in situ. In in vitro studies on HeLa and MDA-MB-231 cell lines, a synergistic effect was observed with the impregnated CasIII-ia on ZnONPs. The anticancer activity had an increase in cellular inhibition, depending on the dose of exposure to UV-vis irradiation. In in vivo studies utilized zebrafish models for xenotransplanting stained MDA-MB-231 cells and testing the effectiveness of Cas-ZnONPs treatment. The treatment successfully eliminated cancer cells, both when combined with Photodynamic Therapy (PDT) and when used alone. However, a significantly higher concentration (50 times) of Cas-ZnONPs was required in the absence of PDT. This demonstrates the potential of Cas-ZnONPs in cancer treatment, especially when combined with PDT.

Fluorescent probe for early mitochondrial voltage dynamics.

Mitochondrial voltage dynamics plays a crucial role in cell healthy and disease. Here, a new fluorescent probe to monitor mitochondrial early voltage variations is described. The slowly permeant probe is retained in mitochondria during measurements to avoid interferences from natural membrane potential by incorporating an hydrolizable ester function. Voltage, local polarity, pH parameters and transmembrane dynamics were found to be deeply correlated opening a approach in mitochondrial sensing.

Tuning the Cell Uptake and Subcellular Distribution in BODIPY-Carboranyl Dyads: An Experimental and Theoretical Study.

A set of BODIPY-carboranyl dyads synthesized by a Sonogashira cross-coupling reaction, where different C-substituted ortho- and meta-carboranyl fragments have been linked to a BODIPY fluorophore is described. Chemical, photophysical and physicochemical analyses are presented, including NMR and single XRD experiments, optical absorption/emission studies and partition coefficient (log P) measurements. These studies, supported by DFT computations (M06-2X/6-31G**), provide an explanation to the largely divergent cell income that these fluorescent carboranyl-based fluorophores display, for which a structural or physicochemical explanation remains elusive. By studying the cell uptake efficiency and subcellular localization for our set of dyads on living HeLa cells, we tracked the origins of these differences to significant variations in their static dipole moments and partition coefficients, which tune their ability to interact with lipophilic microenvironments in cells. Remarkably, m-carboranyl-BODIPY derivatives with a higher lipophilicity are much better internalised by cells than their homologous with o-carborane, suggesting that m-isomers are potentially better theranostic agents for in vitro bioimaging and boron carriers for boron neutron capture therapy.

Diversity-Oriented Synthesis of Highly Fluorescent Fused Isoquinolines for Specific Subcellular Localization.

A multicomponent diversity-oriented synthesis of new highly emissive tetracyclic isoquinolines that target specific organelles is described. The title compounds were prepared via a three-step protocol starting with an Ugi four-component reaction, followed by either an intramolecular alkyne hydroarylation and subsequent alkene isomerization or through a Pomeranz-Fritsch-type cyclization with a final intramolecular Heck reaction. Subcellular localization studies of these compounds using green channel confocal microscopy revealed remarkable and distinctive distribution patterns in live cells, showing an unprecedented high selectivity and imaging contrast. The differentiated organelle visualization-including localizers for mitochondria, lysosomes, Golgi apparatus, endoplasmic reticulum, and plasma membrane-was achieved by varying the nature of the tetracyclic system and substituent pattern, changing the original four-component set in the starting Ugi reaction.

Unravelling the modus-operandi of chromenylium-cyanine fluorescent probes: a case study.

Small-molecule fluorescent probes having optimized optical properties, such as high photostability and brightness, local microenvironment sensitivity and specific subcellular localizations, are increasingly available. Although the basis for designing efficient fluorophores for bioimaging applications is well established, implementing an improvement in a given photophysical characteristic always tends to compromise another optical property. This problem has enormous consequences for in vivo imaging, where ensuring a specific localization and precise control of the probe response is challenging. Herein we discuss a fluorescent probe, CC334, as a case study of the chromenylium-cyanine family that commonly exhibits highly complex photophysical schemes and highly interfered bioanalytical responses. By an exhaustive and concise analysis of the CC334 optical responses including detailed spectroscopic calibrations, steady-state microenvironment effects, ultrafast photophysics analysis and computational studies, we elucidate a new strategy to apply the probe in the singlet oxygen reactive oxygen species (1O2-ROS) monitoring using in vitro and in vivo models. The probe provides a new avenue for designing fluorescent probes to understand the dynamic behavior of subcellular environments.

Tracking mitochondrial 1O2-ROS production through a differential mitochondria-nucleoli fluorescent probe.

The dual-emissive fluorescent probe described here enabled dynamic tracking of singlet oxygen (1O2)-ROS species production and localization dynamics between the mitochondria and nucleoli in the presence of agents perturbing the mitochondrial membrane potential and under a photodynamic (PDT) system. Local structural information during the probe-1O2 interaction was followed by spectrally resolved confocal microscopy.