Recent advances in phototheranostics emphasize the unique potential of porphyrin-based compounds in dual-function strategies combining photodynamic therapy (PDT) and optical imaging (1,2). The aim of this study was to explore the potential of metal complexes of designed porphyrinoids for either antimicrobial photodynamic inactivation (PDI) or tumor-targeted PDT and imaging. A library of zinc(II)-, palladium(II)-, and platinum(II)-coordinated porphyrins, phthalocyanines, and bacteriochlorins was evaluated. Photophysical properties were characterized using advanced spectroscopic and photochemical techniques, including time-resolved singlet oxygen phosphorescence, EPR spin trapping. Fluorescence confocal microscopy, transmission electron microscopy, and real-time ROS detection were used to assess biological effects. Biological efficacy was evaluated in planktonic and biofilm cultures of multidrug-resistant (MDR) bacteria, infected human keratinocytes, and patient-derived hiPSC tumor organoids, followed by validation in murine models of bacterial wound infections and CT26 colon carcinoma. Zn(II) and Pd(II) porphyrins exhibited outstanding PDI activity, including complete eradication of S. aureus biofilms and inhibition of bacterial invasion into mammalian cells (3).
To extend therapeutic applications to cancer diagnosis and therapy, further modification of macrocycle was employed to shift absorption toward the near infrared (NIR). Among the compounds studied, the sulfonamide bacteriochlorin (F₄BMet) and Zn(II) phthalocyanine (ZnSO₂tBu) showed superior performance. Both displayed high singlet oxygen quantum yields, strong NIR absorption/emission, and tumor-selective accumulation. In CT26-bearing mice, ZnSO₂tBu induced 84% complete tumor regression following vascular-targeted PDT (4), while F₄BMet enabled 30% long-term cures and optical tumor tracking (5). 3D fluorescence imaging, histopathological analysis, and in vivo pharmacokinetic studies confirmed selective photodamage and mechanistic engagement.
Finally, our most recent results on a novel class of tetrapyrrolic conjugates functionalized with acetaminophen moieties for cyclooxygenase-2 targeted PDT. These bioconjugates were rationally designed to enhance tumor selectivity by exploiting COX-2 overexpression in the tumor microenvironment. The lead compound exhibited excellent tumor accumulation, vascular-targeted PDT efficacy (80% long-term cures in CT26-bearing mice), and modulation of prostaglandin and VEGF signaling pathways. Their performance supports the feasibility of receptor-guided molecular design in phototheranostics.
All these findings demonstrate that precise control over metal coordination, macrocyclic structure, and formulation enables the development of clinically relevant porphyrinoid-based agents for image-guided eradication of infectious and neoplastic lesions.