A Novel Photothermal Nanocrystals of Cu_7S_4 Hollow Structure for Efficient Ablation of Cancer Cells

Cu2-x S nanocrystals(NCs), characterized by low cost, low toxicity, high stability and high photothermal conversion efficiency, provide promising platforms as photothermal agents. Herein, a novel twostep synthesis has been developed for Cu7S4 nanocrystals with hollow structure using the as-prepared copper nanoparticles as starting a solid precursor followed by hot-injection of sulfide source.The Cu7S4 NCs exhibit intense absorption band at Near-infrared(NIR) wavelengths due to localized surface plasmon resonance(LSPR)mode, which can effectively convert 980 nm-laser energy into heat.Moreover, the localized high temperature created by Cu7S4 NCs under NIR irradiation could result in efficient photothermal ablation(PTA) of cancer cells in vivo, demonstrating a novel and promising photothermal nanomaterials.

Super-resolution imaging for in situ monitoring sub-cellular micro-dynamics of small molecule drug

Small molecule drugs play a pivotal role in the arsenal of anticancer pharmacological agents. Nonetheless, their small size poses a challenge when directly visualizing their localization, distribution, mechanism of action (MOA), and target engagement at the subcellular level in real time. We propose a strategy for developing triple-functioning drug beacons that seamlessly integrate therapeutically relevant bioactivity, precise subcellular localization, and direct visualization capabilities within a single molecular entity. As a proof of concept, we have meticulously designed and constructed a boronic acid fluorescence drug beacon using coumarin–hemicyanine (CHB). Our CHB design includes three pivotal features: a boronic acid moiety that binds both adenosine triphosphate (ATP) and adenosine diphosphate (ADP), thus depleting their levels and disrupting the energy supply within mitochondria;a positively charged component that targets the drug beacon to mitochondria;and a sizeable conjugated luminophore that emits fluorescence, facilitating the application of structured illumination microscopy (SIM). Our study indicates the exceptional responsiveness of our proof-of-concept drug beacon to ADP and ATP, its efficacy in inhibiting tumor growth, and its ability to facilitate the tracking of ADP and ATP distribution around the mitochondrial cristae. Furthermore, our investigation reveals that the micro-dynamics of CHB induce mitochondrial dysfunction by causing damage to the mitochondrial cristae and mitochondrial DNA. Altogether, our findings highlight the potential of SIM in conjunction with visual drug design as a potent tool for monitoring the in situ MOA of small molecule anticancer compounds. This approach represents a crucial advancement in addressing a current challenge within the field of small molecule drug discovery and validation.