Molecular Engineering Design of Enhanced Donor–Acceptor Therapeutic Reagent for Efficient Image‐Guided Photodynamic Therapy

The greatest barrier to the further development and clinical application of tumor image-guided photodynamic therapy (PDT), is the inconsistency between the fluorescence intensity and singlet oxygen generation yield of the photosensitizer under light excitation. Herein, a novel donor-acceptor (D-A) system is designed from the point of molecular selection by wrapping a classical porphyrin molecule (5,10,15,20-tetraphenylphorphyrin, H2 TPP) as an acceptor into conjugated polymer (Poly[N,N'-bis(4-butylpheny)-N,N'-bis(phenyl)benzidine], ADS254BE) as a donor through fluorescence resonance energy transfer (FRET) mechanism, which exhibits bright red emission centered at 650 nm (quantum yield, 0.12), relatively large Stoke shift of 276 nm, enhanced singlet oxygen generation rate of 0.73, and excellent photostability. The investigations on distribution and killing effect of nanomaterials in cancer cells reveal that ADS254BE/H2 TPP NPs can accumulate in the cytoplasm for imaging while simultaneously producing a large amount of singlet oxygen to remarkably kill cancer cells, which can be used for real-time image-guided PDT. In the xenograft tumor model, real-time imaging and long-term tracing in tumor tissue with ADS254BE/H2 TPP NPs disclose that the growth of lung cancer in mice can be effectively inhibited during in situ imaging. From the standpoint of molecular engineering design, this work provides a feasible strategy for novel D-A systems to improve the development of image-guided PDT.