Department of Chemical Engineering, National Taiwan University of Science and Technology, 43, Section 4, Keelung Road, Taipei 10607, Taiwan, Republic of China.
Department of Chemistry, National Tsing Hua University, 101, Section 2, Guangfu Road, Hsinchu 30013, Taiwan, Republic of China.
Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:179-189. doi: 10.1016/j.msec.2019.03.074. Epub 2019 Mar 26.
Multimodal therapy is an emerging medical intervention to overcome the current limitation in cancer therapy combining treatment modalities with different mechanisms of action to eradicate tumors. This study demonstrates a targeted multifunctional bovine serum albumin (BSA)-functionalized CuFeS/chlorin e6 (Ce6) for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) effects. The CuFeS nanocrystals were synthesized through a simple heating-up approach and transferred into an aqueous phase using BSA in an ultrasonic-assisted microemulsion method. The as-prepared CuFeS@BSA nanoparticles further conjugated with folic acid (FA) followed by attachment of Ce6 to form the Ce6:CuFeS@BSA-FA nanohybrid with improved solubility and strong near-infrared (NIR) absorbance and fluorescence. It is the first report to fabricate the targeted Ce6:CuFeS@BSA-FA hybrid and evaluates their synergistic PTT/PDT effect using a single laser. The Ce6:CuFeS@BSA-FA hybrid showed lower toxicity in vitro (HeLa and HepG2 cells) and in vivo (zebrafish embryos), while they are selectively recognized and internalized by HeLa cells that over-express folate receptors. Compared to each modality applied separately, the combined single-laser-induced PTT and PDT treatment showed the enhanced generation of heat and reactive oxygen species (ROS) with synergistic cancer killing under 671 nm laser irradiation (10 min, 1 W/cm). As a biocompatible targeted nanoprobe, the multifunctional nanohybrid holds promise in combined PDT/PTT synergistic therapy to achieve better efficacy.
多模态治疗是一种新兴的医学干预手段，旨在克服当前癌症治疗的局限性，将具有不同作用机制的治疗方式相结合，以消灭肿瘤。本研究展示了一种靶向多功能牛血清白蛋白（BSA）功能化的 CuFeS/叶绿素 e6（Ce6），用于协同光热治疗（PTT）和光动力治疗（PDT）。通过简单的加热方法合成了 CuFeS 纳米晶体，并在超声辅助微乳液法中使用 BSA 将其转化为水相。所制备的 CuFeS@BSA 纳米粒子进一步与叶酸（FA）偶联，然后附着 Ce6 形成 Ce6:CuFeS@BSA-FA 纳米杂化物，提高了其溶解度和强近红外（NIR）吸收和荧光。这是首次制备靶向 Ce6:CuFeS@BSA-FA 杂化物，并使用单一激光评估其协同 PTT/PDT 效应。Ce6:CuFeS@BSA-FA 杂化物在体外（HeLa 和 HepG2 细胞）和体内（斑马鱼胚胎）表现出较低的毒性，而它们可以被过表达叶酸受体的 HeLa 细胞选择性识别和内化。与每种单独应用的模式相比，在 671nm 激光照射下（10min，1W/cm），联合单激光诱导的 PTT 和 PDT 治疗显示出增强的热和活性氧（ROS）的产生，具有协同的癌症杀伤作用。作为一种生物相容性的靶向纳米探针，多功能纳米杂化物有望在联合 PDT/PTT 协同治疗中实现更好的疗效。
