Unlike conventional carrier–based drug delivery systems, anticancer nano–prodrugs are carrier–free nanoparticles with a high drug loading capacity that have shown approximately 10–fold higher therapeutic efficacy compared to marketed drugs in animal experiments. However, their detailed biological behavior, particularly their cellular membrane permeability and intracellular degradation processes, remained unclear. Using fluorescence microscopy based on Förster resonance energy transfer (FRET), we successfully tracked the cellular uptake and intracellular dynamics of nano–prodrugs, which had previously been difficult to observe. This paper describes the comprehensive process from endocytic cellular uptake to intracellular particle degradation and conversion into active drug molecules.

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We have investigated translocation of nanoparticles (NPs) across cell membrane under a weak external electric field. In this review, we introduced a molecular dynamics simulation study on NP translocation across cholesterol– containing phospholipid membranes under an electric field. A unique finding was presented, namely that NP can translocate directly across even cholesterol–containing membrane without irreversible membrane disruption. We also introduced an experimental study on the membrane crossing of an intracellular delivery compound using charged NP and a weak external electric field. This study demonstrated that adding NPs under a weak electric field can enhance permeability of a model delivery compound (dextran) across a cell membrane with less damage.

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Metal complexes exhibit different features (magnetism, light absorption, fluorescence, etc.), which are expected to function as contrasting and/or therapeutic agents in medical treatment. We have studied two series of metal complexes, lanthanide–thiacalix[4]arene–p–tetrasulfonate (LnIII–TCAS) complexes and diradical–platinum (PtII) complexes toward cancer diagnosis and treatment. Gadolinium (GdIII)–TCAS complexes can be used for magnetic resonance imaging (MRI) and neutron capture therapy (NCT) due to the magnetism and neutron capture reaction of GdIII. Diradical–PtII complexes can act as contrasting agents for photoacoustic imaging (PAI) and therapeutic agents for photothermal therapy (PTT). In this article, we will introduce the performance of these two metal complexes and their applications to nanomedicine targeting cancer, while also explaining the principles of imaging and treatment modalities.

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Temperature at the microscopic level is a critical physical parameter in biological systems. In recent years, we have been developing chemical approaches for measuring and controlling intracellular temperature. For instance, we have generated temperature–sensitive fluorescent dyes capable of sensing intracellular temperature, enabling intracellular thermometry. By targeting these dyes to specific organelles, we have achieved organelle–specific thermometry. Using this approach, we successfully visualized thermogenesis in brown adipocytes, a model thermogenic cell. In addition to measurement, we have established methods for creating localized heat spots within live cells. By utilizing photothermal dyes that convert light into heat and can be selectively accumulated in cells, we have created tiny heat spots. These tools have allowed thermodynamic manipulation of cellular functions, such as inducing cell death and muscle contraction. We hope this article inspires researchers across various fields by highlighting the critical role of microscopic temperature.

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The concept of “precision medicine”, which analyzes genomic information at the individual patient level and utilizes it for treatment, is rapidly expanding. Gene therapy and nucleic acid therapy, which complement and suppress the expression of disease–related genes respectively, are expected to become powerful technologies to meet unmet medical needs. Notably, an RNA vaccine against SARS–CoV–2 has been approved. This historical success now accelerates the innovation of mRNA–based medicine worldwide. In these application, lipid nanoparticles (LNPs) are the key delivery system of mRNA and nucleic acids. In this manuscript, the basic concept and design of the intracellular environment–responsive lipid will be summarized. In parallel, I will introduce our original lipid–like materials (ssPalm: SS–cleavable and pH–activated lipid–like material), and application using these materials.

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Since magnetic nanoparticles generate heat in a high–frequency alternating magnetic field, researchers have conducted magnetic hyperthermia, in which magnetic nanoparticles are delivered to tumors and magnetic–field– induced heating is used to destroy the tumor. If magnetic nanoparticles can be delivered to tumors, tumors can be heated by irradiating an alternating magnetic field from outside the body, enabling specific hyperthermia to kill only cancer cells with heat. The authors have previously produced magnetite cationic liposomes in which magnetic nanoparticles are embedded in liposomes made of positively charged lipids, antibody–conjugated magnetite nanoparticles in which antibody drugs are bound to the surface of magnetic nanoparticles, and mitochondria–targeted magnetite nanoparticles in which magnetic nanoparticles are coated with a polymer containing a compound that specifically accumulates in mitochondria. In addition, we have developed melanoma–targeted magnetite nanoparticles in which NPrCAP, a drug that molecularly targets the mechanism by which melanoma is bound to magnetic nanoparticles. In this paper, we will describe these functional magnetic nanoparticles and discuss the future prospects.

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Nanofiltration membrane has been developed specifically targeting Direct Lithium Extraction (DLE) from brine, since the demand for lithium–ion batteries continues to grow following the global trends toward decarbonization and electrification. This increasing demand necessitates DLE from more readily–available and environmentally–friendly methods compared to traditional open–pit mining. Our newly–developed nanofiltration element “FilmTec^TM LiNE–XD” enables high lithium passage from typical chloride–rich Li–brine streams and an excellent selectivity over divalent metals such as magnesium. In addition, LiNE–XD provides robust and reliable operations with long–lasting service time under minimized energy consumption; > 30% energy saving compared to other options.

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