Low-power laser irradiation of red light has been recognized as a promising tool across a vast variety of biomedical applications. However, deep understanding of the molecular mechanisms behind laser-induced cellular effects remains a significant challenge. Here, we investigated mechanisms involved in the death process in human hepatic cell line Huh7 at a laser irradiation. We decoupled distinct cell death pathways targeted by laser irradiations of different powers. Our data demonstrate that high dose laser irradiation exhibited the highest levels of total reactive oxygen species production, leading to cyclophilin D-related necrosis via the mitochondrial permeability transition. On the contrary, low dose laser irradiation resulted in the nuclear accumulation of superoxide and apoptosis execution. Our findings offer a novel insight into laser-induced cellular responses, and reveal distinct cell death pathways triggered by laser irradiation. The observed link between mitochondria depolarization and triggering ROS could be a fundamental phenomenon in laser-induced cellular responses.

Remote control of the interaction of magnetic nanoparticles with cells is fundamental to any potential downstream applications of magnetic nanoparticles such as gene and drug delivery vehicles and magnetic cell labeling. Thus, approaches based on the application of external magnetic fields to increase the efficiency of magnetic cell labeling are desirable. Here, we report a simple approach that enhances magnetic cell labeling using pulsed magnetic fields. The rate of uptake of superparamagnetic iron oxide nanoparticles (SPIONs) and transport across the cell membrane were enhanced upon application of a high intensity (7 T) short pulse width (∼15 μs) magnetic field. We present a quantitative analysis and mechanistic explanation of how a pulsed magnetic field influences the uptake of SPIONs by cells. Our findings offer insights into the mechanics of how pulsed magnetic fields can be effectively used to optimize magnetic cell labeling, which can provide a basis for better controlled biomedical applications of SPIONs.

Proteins of the mammalian target of rapamycin (mTOR) signaling axis are overexpressed or mutated in cancers. However, clinical inhibition of mTOR signaling as a therapeutic strategy in oncology shows rather limited progress. Nanoparticle-based mTOR targeted therapy proposes an attractive therapeutic option for various types of cancers. Along with the progress in the biomedical applications of nanoparticles, we start to realize the challenges and opportunities that lie ahead. Here, we critically analyze the current literature on the modulation of mTOR activity by nanoparticles, demonstrate the complexity of cellular responses to functionalized nanoparticles, and underline challenges lying in the identification of the molecular mechanisms of mTOR signaling affected by nanoparticles. We propose the idea that subcytotoxic doses of nanoparticles could be relevant for the induction of subcellular structural changes with possible involvement of mTORC1 signaling. The evaluation of the mechanisms and therapeutic effects of nanoparticle-based mTOR modulation will provide fundamental knowledge which could help in developing safe and efficient nano-therapeutics.