Construction of mannosylated glycol-nanoparticles for near-infrared bioimaging and photodynamic therapy targeting breast cancer cells
TL;DR
Two donor–π–acceptor type photosensitizers, TC1 and TC2, are designed by bridging electron-rich carbazole with electron-withdrawing tricyanofuran (TCF) via thiophene or EDOT moieties as promising targeted theranostic agents for NIR imaging and PDT of breast cancer.
Abstract
Photodynamic therapy (PDT) offers a promising approach for cancer treatment, but developing photosensitizers (PSs) with tumor targeting and near-infrared (NIR) imaging capabilities remains challenging. Herein, we designed two donor–π–acceptor (D–π–A) type photosensitizers, TC1 and TC2, by bridging electron-rich carbazole with electron-withdrawing tricyanofuran (TCF) via thiophene or EDOT moieties. Both PSs exhibited broad absorption, NIR fluorescence emission (>650 nm), and efficient type-I/II reactive oxygen species (ROS) generation under light irradiation. To improve aqueous dispersibility and breast cancer targeting, we conjugated PEGylated mannose to TC1 and TC2, yielding glycol-nanoparticles TC1M and TC2M. These nanoparticles maintained desirable NIR optical properties and ROS generation capacity while exhibiting excellent biocompatibility. Notably, mannose receptor-mediated endocytosis enabled selective uptake by MDA-MB-231 breast cancer cells over normal bEnd.3 cells, allowing targeted fluorescence imaging. Furthermore, TC2M demonstrated potent photodynamic activity, reducing cell viability to 23.15% at 20 µM under light irradiation through efficient intracellular ROS generation. This study presents mannose-functionalized glycol-nanoparticles as promising targeted theranostic agents for NIR imaging and PDT of breast cancer.