Study on cellular uptake of a hydrophobic near-infrared-absorbing diradical-platinum(II) complex solubilized by albumin using hyperspectral imaging, spectrophotometry, and spectrofluorimetry.

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 Kb = 5.91 × 104 M-1 could be estimated upon fluorescence quenching analysis of BSA upon binding of PtL2; Kb is two orders of magnitude smaller than that of albumin-common drugs. Considering the small Kb 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.

MRI Contrasting Agent Based on Mn-MOF-74 Nanoparticles with Coordinatively Unsaturated Sites.

PURPOSE: The development of magnetic resonance imaging (MRI) contrasting agents (CAs) that are safer and have a higher relaxivity than Gd(III)-based agents is a significant research topic. Herein, we propose the use of a Mn-based metal organic framework (MOF), Mn-MOF-74, characterized by a safe paramagnetic center, a coordinatively unsaturated site (CUS) for aquation, and a long rotational correlation time, endowing high relaxivity. Furthermore, biocompatibility and delivery to the tumor are generally expected for MOFs that are obtainable in the nanometer size range. PROCEDURE: Drop-wise mixing of 2,5-dihydroxyterephthalic acid (DHTP) and Mn(II) acetate yielded Mn-MOF-74 with a diameter of < 150 nm, which was then modified with 1-fivefold higher amounts of poly(ethylene glycol) (M.W. = 5000) to afford MOFs stably dispersed in water for at least 24 h. RESULTS: The longitudinal and transverse relaxivity of the PEG-modified MOF was in the range of r1 = 8.08-13.5 and r2 = 32.7-46.8 mM-1 s-1, respectively (1.0 T, 23.7-23.9 °C), being larger than those of typical Gd(III)- and Mn(II)-based CAs of single-nuclear metal complexes. The in vivo imaging of a tumor-bearing mouse clearly showed that the tumor could be readily recognized due to signal enhancement (117%) in T1-weighted images, whereas other tissues showed small signal changes. CONCLUSIONS: These results suggest that PEG-Mn-MOF-74 can be passively delivered to tumors and can act as a high-relaxivity T1 agent.

Emergence of the super antenna effect in mixed crystals of ytterbium and lutetium complexes showing near-infrared luminescence.

The synthesis of luminescent molecular crystalline materials requires a good understanding of the luminescence properties of crystals in which many molecules are densely packed. Previously, we studied the near-infrared (NIR) luminescence of a trivalent ytterbium (Yb(iii)) complex with a Schiff base ligand, tris[2-(5-methylsalicylideneimino)ethyl]amine (H3L). Herein, we extended our study on the Yb complex (YbL) to enhance and understand its solid-state luminescence via mixed crystallization with the lutetium complex (LuL). We prepared (YbL) x (LuL)1-x mixed crystals (x = 0.01, 0.05, 0.1, 0.2, 0.3, 0.5, and 0.7) and studied their NIR luminescence properties. The NIR luminescence intensity per Yb(iii) ion for (YbL)0.01(LuL)0.99 was determined to be two orders of magnitude larger than that for YbL. The excitation spectral shape of (YbL)0.01(LuL)0.99 was different from the absorption spectral shape of YbL but similar to that of LuL. We attribute this observation to the emergence of an intermolecular energy-migration path. In the mixed crystals, LuL molecules acted as a light-harvesting super antenna for Yb(iii) luminescence. Decay measurements of the NIR luminescence for (YbL) x (LuL)1-x with x > 0.2 showed mono-exponential decay, while (YbL) x (LuL)1-x with x < 0.1 showed a grow-in component, which reflected the lifetime of the intermediate state for energy migration. The decay lifetime values tended to increase with decreasing x, suggesting that Yb(iii) isolation resulted in a reduction in concentration quenching. We propose that the luminescence enhancement in the highly Yb-diluted conditions was mainly caused by an increase in the super antenna effect.

Selective crystallization of dysprosium complex from neodymium/dysprosium mixture enabled by cooperation of coordination and crystallization.

Designing a molecular-level Ln3+ separation system remains a challenge for developing next-generation separation methodologies. Herein, we report crystallization-based Nd3+/Dy3+ separation using a tripodal Schiff base ligand. Highly selective crystallization of the Dy3+ complex was enabled by cooperation between the coordination and crystallization processes.

Short Radiative Lifetime and Non-Triplet Sensitization in Near-Infrared-Luminescent Yb(III) Complex with Tripodal Schiff Base.

We prepared Ln(III) (Ln=Eu, Gd, and Yb) complexes with a tripodal Schiff base, tris[2-(5-methylsalicylideneimino)ethyl]amine (H3 L) and studied their photophysical properties. Upon ligand excitation, YbL showed Yb(III)-centered luminescence in the near-infrared region. While the overall quantum yield (0.60(1)%) of YbL in acetonitrile was moderate among the reported values for Yb(III) complexes, its radiative lifetime (0.33(2) ms) was significantly shorter than those reported previously. We propose that the ligand-to-metal charge-transfer (LMCT) state mediated the sensitization in YbL. The emission and excitation spectra of EuL indicated the participation of the LMCT state in the sensitization. The radiative lifetime (0.84(7) ms) for EuL in the solid state was rather short compared to those of reported Eu(III) complexes. Our results show that the Yb(III) complex with the Schiff base ligand has two features: the short radiative lifetime and the non-triplet sensitization path.

Photostable near-infrared-absorbing diradical-platinum(ii) complex solubilized by albumin toward a cancer photothermal therapy agent.

A hydrophobic diradical-platinum(ii) complex was solubilized in aqueous solutions by using bovine serum albumin and exhibited photothermal conversion under near-infrared (NIR) light irradiation. The complex was introduced into cancer cells and induced cell death upon absorption of NIR. These results imply that the complex can function as a photothermal therapeutic agent.