One change, many benefits : a glycine-modified bacteriochlorin with NIR absorption and a type i photochemical mechanism for versatile photodynamic therapy

Difluorinated sulfonamide porphyrin ($F_{2} PGly$) and bacteriochlorin ($F_{2} BGly$), modified by glycine residues, were synthesized and evaluated for photodynamic therapy (PDT). $F_{2} PGly$ exhibits superior stability and singlet oxygen generation efficiency but features a low-intensity band in the red range ($λ_{max}$ = 639 nm). In contrast, $F_{2} BGly$ shows a favorable, red-shifted absorption spectrum ($λ_{max}$ = 746 nm) that aligns well with phototherapeutic window, facilitating deeper tissue penetration. Moreover, it demonstrates reasonable photostability, necessary for the efficient generation of both singlet oxygen (type II) and oxygen-centered radicals (type I mechanism) which contributes to enhanced therapeutic efficacy. Importantly, the glycine modifications in $F_{2} BGly$ enhance its uptake in MCF-7 cells, known for their resistance to PDT due to efflux transport proteins like LAT1, showing great potential in the cancer cell-targeted PDT. The glycine groups potentially enable $F_{2} BGly$ to bypass these barriers, resulting in increased intracellular accumulation and more effective Reactive Oxygen Species (ROS) generation under illumination. In vivo studies indicated promising vascular-targeted PDT results, with real-time fluorescence imaging used to monitor photosensitizer distribution prior to irradiation. These findings suggest that $F_{2} BGly$ is a promising photosensitizer candidate with enhanced cancer cell selectivity and photodynamic efficiency, meriting further exploration in targeted PDT applications for multiple types of cancers.