Biology subjects

Nomoto, T.

Publications and source records attributed to Nomoto, T..

2 recordsLinked to original sources

bioRxiv2026

Light power density governs local and systemic responses to photodynamic therapy

Photodynamic therapy (PDT) is a promising remedy against tumor cells by light activation of a photosensitizer, and its systemic antitumor effects are commonly attributed to immunogenic cell death and the release of soluble damage-associated molecular patterns (DAMPs). Here, we show that light power density (mW/cm2), which is often treated as a mere technical parameter, determines whether PDT suppresses distant, unirradiated tumors. At an identical light dose (J/cm2), PDT at a low power density sustained singlet oxygen (1O2) generation in tumors, preserved tumor perfusion, and suppressed both irradiated and unirradiated tumors. PDT at a high power density resulted in reduced 1O2 generation, reduced tumor perfusion, and increased programmed death-ligand 1 (PD-L1) expression in unirradiated tumors without inhibiting their growth. Serum levels of soluble DAMPs did not differ between the two conditions, whereas circulating small extracellular vesicles (sEVs) carried distinct protein cargo. Power density is thus a controllable determinant of the systemic effects of PDT, and circulating sEVs are candidate mediators of these effects.

cancer biology↗

bioRxiv2026

Sequentially Self-Assembled Supramolecular Nanocomplexes Enable Systemic Cas9 RNP Delivery and In Vivo Tumor Genome Editing

In vivo genome editing with CRISPR-Cas9 ribonucleoproteins (RNPs) holds substantial therapeutic promise, yet rapid bloodstream clearance and the absence of delivery systems capable of systemic tumor targeting have hindered its clinical translation. Herein, a supramolecular ternary complex platform is reported in which Cas9/sgRNA RNPs are co-assembled with tannic acid (TA) and phenylboronic acid (PBA)-conjugated polymers through sequential self-assembly, producing [~]30 nm core-shell ternary complexes that protect RNPs from enzymatic degradation and dissociate selectively at endosomal pH. Upon intravenous administration in subcutaneous tumor-bearing mice, these ternary complexes exhibit prolonged blood circulation and preferential tumor accumulation, achieving 37.2% gene editing at tumor sites compared with only 1.5% for free RNPs. The platform successfully knocks out previously undruggable oncogenes including mutant KRAS and polo-like kinase 1 (PLK1), markedly suppressing tumor growth in vivo. By integrating sequential supramolecular self-assembly with stimuli-responsive cargo release, this strategy establishes a generalizable framework for systemically administered in vivo CRISPR therapeutics.

bioengineering↗