Active control of pharmacokinetics using light-responsive polymer-drug conjugates for boron neutron capture therapy.

In boron neutron capture therapy (BNCT), boron drugs should exhibit high intratumoral boron concentrations during neutron irradiation, while being cleared from the blood and normal organs. However, it is usually challenging to achieve such tumor accumulation and quick clearance simultaneously in a temporally controlled manner. Here, we developed a polymer-drug conjugate that can actively control the clearance of the drugs from the blood. This polymer-drug conjugate is based on a biocompatible polymer that passively accumulates in tumors. Its side chains were conjugated with the low-molecular-weight boron drugs, which are immediately excreted by the kidneys, via photolabile linkers. In a murine subcutaneous tumor model, the polymer-drug conjugate could accumulate in the tumor with the high boron concentration ratio of the tumor to the surrounding normal tissue (~10) after intravenous injection while a considerable amount remained in the bloodstream as well. Photoirradiation to blood vessels through the skin surface cleaved the linker to release the boron drug in the blood, allowing for its rapid clearance from the bloodstream. Meanwhile, the boron concentration in the tumor which was not photoirradiated could be maintained high, permitting strong BNCT effects. In clinical BNCT, the dose of thermal neutrons to solid tumors is determined by the maximum radiation exposure to normal organs. Thus, our polymer-drug conjugate may enable us to increase the therapeutic radiation dose to tumors in such a practical situation.

Self-Folding Macromolecular Drug Carrier for Cancer Imaging and Therapy.

Nano-sized contrast agents (NCAs) hold potential for highly specific tumor contrast enhancement during magnetic resonance imaging. Given the quantity of contrast agents loaded into a single nano-carrier and the anticipated relaxation effects, the current molecular design approaches its limits. In this study, a novel molecular mechanism to augment the relaxation of NCAs is introduced and demonstrated. NCA formation is driven by the intramolecular self-folding of a single polymer chain that possesses systematically arranged hydrophilic and hydrophobic segments in water. Utilizing this self-folding molecular design, the relaxivity value can be elevated with minimal loading of gadolinium complexes, enabling sharp tumor imaging. Furthermore, the study reveals that this NCA can selectively accumulate into tumor tissues, offering effective anti-tumor results through gadolinium neutron capture therapy. The efficacy and versatility of this self-folding molecular design underscore its promise for cancer diagnosis and treatment.

The structure and formation of giant Marimo (Aegagropila linnaei) in Lake Akan, Japan.

Aegagropila linnaei is a freshwater green alga, which at one time was distributed widely in the northern hemisphere. The aggregate often forms beautiful spherical shapes known as "lake balls" or "Marimo". The population of Marimo has been rapidly decreasing worldwide, and today the large Marimo, with a diameter of more than 12 cm, exit only in Lake Akan in Japan. However, how Marimo grow and maintain their unique spherical shape in natural habitats remains unsolved. Here we show that Marimo are "polished" into spheres by the rotation induced by wind waves. Such a process enhances the water exchange between the interior and exterior of the Marimo, thereby recycling nutrients for growth. Our results provide an intriguing model of a physical environment interacting with biological processes in a self-sustaining ecosystem. We also demonstrate that Marimo have a spherical annual ring structure, and their growth rate is associated with ice cover. The balance between the ecology of Marimo and the water environment in Lake Akan is highly vulnerable and at risk of irreversible degradation. We must endeavor to rescue Marimo from the fate of a "canary in the coal mine" of global climate change.