The People's Hospital of Gaozhou, Maoming, 525200, PR China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, PR China.
Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, PR China.
Biomaterials. 2022 Oct;289:121779. doi: 10.1016/j.biomaterials.2022.121779. Epub 2022 Sep 2.
Due to the aggregation-caused quenching (ACQ) and weak photo-penetrating ability, the application of phototheranostic agents in drug delivery field is greatly limited. Ferroptosis, a newly discovered cell death mode, has not been extensively studied in the field of phototherapy up to now. Here, a new near-infrared II (NIR-II) molecule with aggregation-induced emission (AIE) property (named TSST) co-assembled with DHA-PEG and ferrocene as nanoparticles (DFT-NP), which was rationally designed and synthesized. The DFT-NP exhibited enhanced NIR-II fluorescence, photothermal, photoacoustic, magnetic resonance imaging, AIE and ferroptosis capacities. The NIR-II fluorescence intensity of obtained nanoparticles was improved, owing to the strong interaction between DHA and TSST, which limited the intramolecular rotation restriction and non-radiative attenuation of TSST to discourage energy dissipation in aggregation state. Inspiringly, the generated photothermal effect by DFT-NP can promote the Fenton reaction of ferrocene and HO, resulting in dissolution of the nanoparticles and cancer cells expedited ferroptosis via accumulation lipid free radicals of DHA. The released TSST enhanced the photothermal and photoacoustic imaging effects through removing the DHA restriction to restore the non-radiative attenuation. This work is the first example of nanoparticles that integrates four-mode imaging, photothermal and ferroptosis-induced therapy functions, which offers great advantages for potential clinical applications.
由于聚集引起的猝灭（ACQ）和光穿透能力弱，光治疗剂在药物输送领域的应用受到了极大的限制。铁死亡，一种新发现的细胞死亡方式，在光疗领域尚未得到广泛研究。在这里，一种具有聚集诱导发射（AIE）特性的新型近红外 II（NIR-II）分子（命名为 TSST）与 DHA-PEG 和二茂铁共组装成纳米颗粒（DFT-NP），这是一种合理设计和合成的纳米颗粒。DFT-NP 表现出增强的近红外 II 荧光、光热、光声、磁共振成像、AIE 和铁死亡能力。由于 DHA 与 TSST 之间的强相互作用，获得的纳米颗粒的近红外 II 荧光强度得到了提高，这限制了 TSST 的分子内旋转限制和非辐射衰减，以阻止聚集状态下的能量耗散。令人鼓舞的是，DFT-NP 产生的光热效应可以促进二茂铁和 HO 的芬顿反应，导致纳米颗粒的溶解和癌细胞通过积累 DHA 的游离脂质自由基加速铁死亡。释放的 TSST 通过去除 DHA 的限制来恢复非辐射衰减，增强了光热和光声成像效应。这项工作是首例将四种模式成像、光热和铁死亡诱导治疗功能集成在一体的纳米颗粒，为潜在的临床应用提供了巨大的优势。
