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Phototherapeutic agents exhibit excellent performance in both Type I photodynamic therapy (PDT) and photothermal therapy (PTT); however, designing mitochondria-targeted phototherapeutic agents (PTAs) remains challenging. Feng Shouhua from Jilin University and Ma Pingan’s team from the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, proposed the development of multifunctional PTAs using benzene, furan, and thiophene as π-bridges. In particular, the STB with thiophene as a π-bridge benefits from stronger donor-acceptor (D−A) interactions, reducing the singlet-triplet energy gap (ΔES1‑T1), allowing more free molecular intramolecular rotation, and exhibiting excellent near-infrared (NIR) emission, effective Type I reactive oxygen species (ROS) generation, and relatively high photothermal conversion efficiency (PCE).

Figure 1: Material structure and preparation and application of mitochondria-targeted STB-NP in multimodal imaging-guided PDT and PTT synergistic therapy.

Figure 2: Photophysical properties and theoretical calculations

Figure 3: Photodynamic characteristics

Figure 4: Photothermal properties

Figure 5: In vitro phototherapeutic performance

Figure 6: Multimodal imaging-guided in vivo phototherapy
In vitro and in vivo experiments indicate that the positively charged STB not only actively targets the mitochondria of tumor cells but also exhibits strong anti-tumor effects and good in vivo imaging capabilities. This work ingeniously establishes a win-win strategy through π-bridge engineering, breaking the balance barrier between ROS generation and photothermal conversion, promoting the dual enhancement of PDT and PTT performance, and stimulating the development of multimodal imaging-guided precise phototherapy for cancer.
In summary, STB-NP performs well both in vitro and in vivo, demonstrating active targeting accumulation in tumor regions, real-time in vivo fluorescence imaging capabilities, and significant tumor suppression treatment with low side effects.


Original link: https://pubs.acs.org/doi/full/10.1021/acsnano.3c06542
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