Background: Efficient and specific induction of cell death in liver cancer is urgently needed. In this study, we aimed to design an exosome-based platform to deliver ferroptosis inducer (Erastin, Er) and photosensitizer (Rose Bengal, RB) into tumor tissues with high specificity./nMethods: Exosome donor cells (HEK293T) were transfected with control or CD47-overexpressing plasmid. Exosomes were isolated and loaded with Er and RB via sonication method. Hepa1-6 cell xenograft C57BL/6 model was injected with control and engineered exosomes via tail vein. In vivo distribution of the injected exosomes was analyzed via tracking the fluorescence labeled exosomes. Photodynamic therapy was conducted by 532 nm laser irradiation. The therapeutic effects on hepatocellular carcinoma and toxic side-effects were systemically analyzed./nResults: CD47 was efficiently loaded on the exosomes from the donor cells when CD47 was forced expressed by transfection. CD47 surface functionalization (Exos^CD47) made the exosomes effectively escape the phagocytosis of mononuclear phagocyte system (MPS), and thus increased the distribution in tumor tissues. Erastin and RB could be effectively encapsulated into exosomes after sonication, and the drug-loaded exosomes (Er/RB@Exos^CD47) strongly induced ferroptosis both in vitro and in vivo in tumor cells after irradiation of 532 nm laser. Moreover, compared with the control exosomes (Er/RB@Exos^Ctrl), Er/RB@Exos^CD47 displayed much lower toxicity in liver./nConclusion: The engineered exosomes composed of CD47, Erastin, and Rose Bengal, induce obvious ferroptosis in hepatocellular carcinoma (HCC) with minimized toxicity in liver and kidney. The proposed exosomes would provide a promising strategy to treat types of malignant tumors.

中文翻译：

---

设计外泌体，通过化学光动力疗法靶向有效诱导癌症铁死亡

背景：迫切需要有效且特异性地诱导肝癌细胞死亡。在本研究中，我们旨在设计一个基于外泌体的平台，以高特异性将铁死亡诱导剂（Erastin，Er）和光敏剂（Rose Bengal，RB）递送到肿瘤组织中。/n方法：外泌体供体细胞（HEK293T）转染对照或CD47过表达质粒。通过超声处理方法分离外泌体并负载 Er 和 RB。Hepa1-6细胞异种移植物C57BL/6模型通过尾静脉注射对照和工程外泌体。通过跟踪荧光标记的外泌体来分析注射的外泌体的体内分布。通过532 nm激光照射进行光动力治疗。系统分析了对肝细胞癌的治疗效果和毒副作用。/n结果：当通过转染强制表达CD47时，CD47被有效地负载到来自供体细胞的外泌体上。CD47表面功能化（Exos ^CD47）使外泌体有效逃避单核吞噬细胞系统（MPS）的吞噬，从而增加在肿瘤组织中的分布。超声处理后Erastin和RB可以有效地封装到外泌体中，并且载药外泌体（Er/RB@Exos ^CD47 ）在532 nm激光照射后在体外和体内强烈诱导肿瘤细胞铁死亡。此外，与对照外泌体（Er/RB@Exos ^Ctrl）相比，Er/RB@Exos ^CD47在肝脏中的毒性要低得多。/n结论：由 CD47、Erastin 和 Rose Bengal 组成的工程外泌体在肝脏中诱导明显的铁死亡。肝细胞癌 (HCC)，对肝脏和肾脏的毒性最小。所提出的外泌体将为治疗多种恶性肿瘤提供一种有前景的策略。