NIR-II-Excited Type-I Conjugated Polymer Photosensitizer for Cancer Photodynamic Therapy.

Abstract

Type-I photodynamic therapy (PDT) is highly effective against hypoxic tumors, with its efficacy further enhanced by near-infrared-II (NIR-II, 1000-1700 nm) excitation, which offers deeper tissue penetration than conventional NIR-I (700-1000 nm). However, most reported organic NIR-II photosensitizers (PSs) are only NIR-II emissive but remain NIR-I-excited. NIR-II-excited type-I PSs are rare and generally limited by low ROS yields, often requiring high-power irradiation with photothermal co-treatment to achieve meaningful therapeutic outcomes. Thus, rationally designing efficient organic type-I PSs directly activated by NIR-II light remains a challenge. Herein, we report a general strategy for designing efficient NIR-II-excited organic Type-I PSs (PNT-PFT NPs) based on linked donor-acceptor through-space charge transfer (CT) for PDT of hypoxic solid tumors. The through-space CT based on linked donor-acceptor pairs redshifts and amplifies the NIR-II absorption of the PNT-PFT NPs. Additionally, the donor-acceptor energy alignment facilitates directional flow of electrons, increasing free-electron yield for O₂-to-ROS conversion. As a result, PNT-PFT NPs efficiently generated ROS and achieved 89.3% tumor inhibition in 4T1 models under low-power 1064 nm irradiation. This study not only offers a general guideline for tailoring NIR-II-excited Type-I PSs via through-space CT in linked donor-acceptor pairs but also provides mechanistic insights into Type-I PS design.