A near-infrared (NIR) absorbing diradical-platinum( ii ) complex solubilized in PBS by albumin can kill MCF-7 cells by the photothermal effect.

Owing to its biopenetrability and minimal invasiveness, near-infrared (NIR) light in the region between 700–1100 nm has attracted attention in cancer diagnosis and therapy. Our group previously reported that the hydrophobic diradical-platinum(II) complex PtL₂ is a promising agent for cancer photothermal therapy (L = 3,5-dibromo-1,2-diiminobenzosemiquinonate radical). Because PtL₂ does not fluoresce, its intercellular uptake of PtL₂ cannot be observed with a fluorescence microscope. In this study, we clarified the uptake and intracellular behavior of PtL₂ solubilized by bovine serum albumin (BSA) using hyperspectral imaging enabling spectrophotometric analysis of the image. The spectral changes in the obtained images indicated that the internalization of PtL₂ was followed by crystallization of the complex during the long incubation period (> 4 h). Additionally, the binding constant K_b = 5.91 × 10⁴ M^–1 could be estimated upon fluorescence quenching analysis of BSA upon binding of PtL₂; K_b is two orders of magnitude smaller than that of albumin–common drugs. Considering the small K_b and low solubility of PtL₂ in water, we ultimately proposed the internalization path and fate of PtL₂ in the cell: release of PtL₂ from BSA near cellular membranes and subsequent cellular uptake via membrane permeation followed by saturation, resulting in crystallization. Graphical abstract

Photothermal therapy (PTT) is a promising approach for cancer treatment that has minimal side effects. It locally heats tumors using agents that convert near-infrared (NIR) light energy into heat. We previously reported that the NIR-absorbing hydrophobic diradical-platinum(II) complex PtL₂ (L = 3,5-dibromo-1,2-diiminobenzosemiquinonato radical) can kill cancer cells through its photothermal conversion ability. In this study, we developed PtL₂-loading nanoparticles (PtL₂@RNPs) for the delivery of the complex to tumors based on the enhanced permeability and retention effect using an amphiphilic block copolymer that can scavenge reactive oxygen species. PtL₂@RNPs exhibited particle diameters of 20–30 nm, an encapsulation efficiency exceeding 90%, and loading capacities of up to 12%. Under NIR laser irradiation, PtL₂@RNPs stably generated heat with almost 100% photothermal conversion efficiency. Although the particles were not modified for cancer cell targeting, their uptake by cancer cells was approximately double that by normal cells. PtL₂@RNPs exhibited NIR absorption and effectively killed cancer cells at a low irradiation power (0.15 W). Normal cells treated with PtL₂@RNPs remained largely undamaged under identical irradiation conditions, demonstrating a cancer-cell-specific photothermal killing effect. These findings can provide insights for future basic studies on cancer cells and the development of effective cancer treatment modalities.

Ln ₃ TCAS ₂ -polyethyleneimine supramolecular nanogels, featuring high drug loading capacity (LC) and enhanced MRI relaxivity, enable efficient intracellular Gd delivery and produce potent neutron capture therapy (NCT) effects.

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.