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Engineered Cell‐Derived Microparticles Bi2Se3/DOX@MPs for Imaging Guided Synergistic Photothermal/Low‐Dose Chemotherapy of Cancer

机译:工程化的细胞衍生微粒Bi2Se3 / DOX @ MPs用于成像指导的协同光热/小剂量化学疗法对癌症的成像

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摘要

Cell‐derived microparticles, which are recognized as nanosized phospholipid bilayer membrane vesicles, have exhibited great potential to serve as drug delivery systems in cancer therapy. However, for the purpose of comprehensive therapy, microparticles decorated with multiple therapeutic components are needed, but effective engineering strategies are limited and still remain enormous challenges. Herein, Bi Se nanodots and doxorubicin hydrochloride (DOX) co‐embedded tumor cell‐derived microparticles (Bi Se /DOX@MPs) are successfully constructed through ultraviolet light irradiation‐induced budding of parent cells which are preloaded with Bi Se nanodots and DOX via electroporation. The multifunctional microparticles are obtained with high controllability and drug‐loading capacity without unfavorable membrane surface destruction, maintaining their excellent intrinsic biological behaviors. Through membrane fusion cellular internalization, Bi Se /DOX@MPs show enhanced cellular internalization and deepened tumor penetration, resulting in extreme cell damage in vitro without considering endosomal escape. Because of their distinguished photothermal performance and tumor homing target capability, Bi Se /DOX@MPs exhibit admirable dual‐modal imaging capacity and outstanding tumor suppression effect. Under 808 nm laser irradiation, intravenous injection of Bi Se /DOX@MPs into H22 tumor‐bearing mice results in remarkably synergistic antitumor efficacy by combining photothermal therapy with low‐dose chemotherapy in vivo. Furthermore, the negligible hemolytic activity, considerable metabolizability, and low systemic toxicity of Bi Se /DOX@MPs imply their distinguished biocompatibility and great potential for tumor theranostics.
机译:细胞来源的微粒,被认为是纳米级的磷脂双层膜囊泡,具有巨大的潜力,可以用作癌症治疗中的药物传递系统。然而,出于全面治疗的目的,需要装饰有多种治疗成分的微粒,但是有效的工程策略有限,仍然是巨大的挑战。此处,Bi Se纳米点和盐酸阿霉素(DOX)共嵌入的肿瘤细胞衍生微粒(Bi Se / DOX @ MPs)是通过紫外线照射诱导的亲代细胞出芽而成功构建的,这些细胞预先通过Bi Se纳米点和DOX加载电穿孔。获得的多功能微粒具有很高的可控性和载药量,并且不会对膜表面造成不利影响,并保持了其优异的固有生物学行为。通过膜融合细胞内在化,Bi Se / DOX @ MPs显示出增强的细胞内在化和加深的肿瘤渗透,从而在不考虑内体逃逸的情况下在体外导致极端的细胞损伤。由于其出色的光热性能和肿瘤归巢靶向能力,Bi Se / DOX @ MPs具有令人赞叹的双峰成像能力和出色的肿瘤抑制作用。在808 nm激光照射下,通过将光热疗法与体内低剂量化学疗法相结合,向H22荷瘤小鼠静脉内注射Bi Se / DOX @ MPs会产生显着的协同抗肿瘤功效。此外,Bi Se / DOX @ MPs的溶血活性,可代谢性和低全身毒性均可以忽略不计,这表明它们具有出色的生物相容性,并具有治疗肿瘤治疗的巨大潜力。

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