Formation of glycosylated nano-photosensitizers for glucose facilitated near-infrared bioimaging and photodynamic therapy against cancer cells.

Abstract

Photodynamic therapy (PDT) integrated with near-infrared (NIR) fluorescence imaging emerges as a promising theranostic approach for precise cancer management, yet the development of biocompatible, targetable, and highly efficient photosensitizers (PSs) is still in urgent demand. Herein, we rationally design and synthesize two novel carbazole-tricyanofuran (TCF)-based donor-π-acceptor (D-π-A) PSs (1 and 2), which exhibit broad absorption, NIR fluorescence, and efficient reactive oxygen species (ROS) generation through both type-I and type-II pathways under 590 nm light irradiation. To improve water solubility, biocompatibility, and tumor-accumulation ability, triglycol (TEG)-functionalized glucose is conjugated onto the PS skeletons to construct glycosylated nano-PSs (1G and 2G). The glucose moieties enable active cellular uptake through overexpressed glucose transporters (GLUTs) on cancer cells. Both 1G and 2G retain favorable NIR optical properties and robust ROS generation capability in aqueous media. In vitro studies demonstrate that 1G and 2G possess negligible dark cytotoxicity and can realize specific NIR fluorescence bioimaging in A549 and HeLa cancer cells. Notably, 2G exhibits excellent photodynamic antitumor efficiency, effectively killing cancer cells upon light irradiation via ROS-mediated cell death. This work provides a feasible glycosylation strategy for constructing NIR-emissive organic nano-photosensitizers, offering a promising candidate for glucose-facilitated cancer theranostics.