Department of Molecular Biomedical Science, North Carolina State University, Raleigh, NC, USA.
Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, NC, USA.
Theranostics. 2020 Feb 10;10(8):3474-3487. doi: 10.7150/thno.39434. eCollection 2020.
Cancer is the second leading cause of death worldwide and patients are in urgent need of therapies that can effectively target cancer with minimal off-target side effects. Exosomes are extracellular nano-shuttles that facilitate intercellular communication between cells and organs. It has been established that tumor-derived exosomes contain a similar protein and lipid composition to that of the cells that secrete them, indicating that exosomes might be uniquely employed as carriers for anti-cancer therapeutics. : We isolated exosomes from two cancer cell lines, then co-cultured each type of cancer cells with these two kinds of exosomes and quantified exosome. HT1080 or Hela exosomes were systemically injected to Nude mice bearing a subcutaneous HT1080 tumor to investigate their cancer-homing behavior. Moreover, cancer cell-derived exosomes were engineered to carry Doxil (a common chemotherapy drug), known as D-exo, were used to detect their target and therapeutic efficacy as anti-cancer drugs. Exosome proteome array analysis were used to reveal the mechanism underly this phenomenon. : Exosomes derived from cancer cells fuse preferentially with their parent cancer cells, in vitro. Systemically injected tumor-derived exosomes home to their original tumor tissues. Moreover, compared to Doxil alone, the drug-loaded exosomes showed enhanced therapeutic retention in tumor tissues and eradicated them more effectively in nude mice. Exosome proteome array analysis revealed distinct integrin expression patterns, which might shed light on the underlying mechanisms that explain the exosomal cancer-homing behavior. : Here we demonstrate that the exosomes' ability to target the parent cancer is a phenomenon that opens up new ways to devise targeted therapies to deliver anti-tumor drugs.
癌症是全球第二大致死原因，患者急需能够有效靶向癌症且副作用最小的治疗方法。外泌体是细胞间通讯的细胞外纳米载体。已经证实，肿瘤来源的外泌体含有与分泌它们的细胞相似的蛋白质和脂质组成，这表明外泌体可能被独特地用作抗癌治疗药物的载体。我们从两种癌细胞系中分离出外泌体，然后将每种类型的癌细胞与这两种外泌体共培养并定量外泌体。将 HT1080 或 Hela 外泌体系统地注射到携带皮下 HT1080 肿瘤的裸鼠中，以研究它们的癌症归巢行为。此外，将癌细胞衍生的外泌体工程化携带 Doxil（一种常用的化疗药物），称为 D-exo，用于检测它们作为抗癌药物的靶向和治疗效果。外泌体蛋白质组阵列分析用于揭示这种现象的机制。癌细胞来源的外泌体在体外优先与它们的母癌细胞融合。系统注射的肿瘤来源的外泌体归巢到它们原来的肿瘤组织。此外，与单独的 Doxil 相比，载药外泌体在肿瘤组织中表现出增强的治疗保留效果，并更有效地根除裸鼠中的肿瘤。外泌体蛋白质组阵列分析揭示了不同的整合素表达模式，这可能为解释外泌体癌症归巢行为的潜在机制提供线索。在这里，我们证明了外泌体靶向母癌细胞的能力是一种现象，为设计靶向治疗方法以递送抗癌药物开辟了新途径。
