De novo design of NIR-II thioxanthene dye and phosphate-driven charge transfer-coupled J-aggregates for high resolution tumor angiography and type I phototherapy against hypoxic tumors

Abstract

Regulating the photophysical properties of NIR-II dyes via atomic engineering to inhibit type II reactive oxygen species (ROS, ¹O₂) generation and only generate type I ROS (O₂˙⁻ and ˙OH), and modulating dye aggregation for fabricating charge transfer (CT)-coupled J-aggregates (J_CT-aggregates) to amplify O₂˙⁻ and ˙OH yield remain major challenges with rare reports. Herein, we de novo designed a NIR-II thioxanthene dye SOH. The heavy atom effect of sulfur and the twisted conjugated skeleton strengthened spin–orbit coupling (SOC) by 9.3-fold and intersystem crossing (ISC) efficiency by 86.5-fold and reduced the lowest triplet excited state (T₁) energy level to 0.959 eV, completely inhibiting ¹O₂ generation while only initiating O₂˙⁻ and ˙OH production, with a photothermal conversion efficiency (PCE) of 42.3%. Furthermore, electrostatic interactions between phosphates (HPO₄²⁻) and the positively charged skeleton of SOH drove the formation of J_CT-aggregates (P-SOH NPs), leading to a prominent redshift (beyond 350 nm) of absorption/emission to 1120/1134 nm, 36.1-fold fluorescence enhancement, 59.0-fold increased type I ROS yield, and PCE elevated to 51.1%. P-SOH NPs achieved NIR-II high-resolution tumor angiography (fluorescence resolution: 0.34 mm, signal-to-background ratio (SBR) = 4.56; photoacoustic resolution: 0.11 mm, SBR = 17.2). The type I phototherapy of P-SOH NPs maintained high tumor cell killing efficiency even in hypoxia, achieving complete tumor ablation.