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Stem cell-mediated delivery of SPIO-loaded gold nanoparticles for the theranosis of liver injury and hepatocellular carcinoma

机译:干细胞介导的载有SPIO的金纳米颗粒的递送,用于肝损伤和肝细胞癌的治疗

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The treatment of liver injuries or hepatocellular carcinoma (HCC) has been hindered by the lack of efficient drug delivery. Even with the help of nanoparticles or other synthetic delivering agents, a large portion of the dose is still sequestered in the reticuloendothelial system. As an alternative, adipose-derived mesenchymal cells (AD-MSCs), which have the capability of homing to the injured liver, can be used as a unique carrier for theranostic agents. Theranostic agents must have the capacity for being non-toxic to host cells during transportation, and for timely activation once they arrive at the injury sites. In this study, we loaded AD-MSCs with superparamagnetic iron oxide-coated gold nanoparticles (SPIO@AuNPs) and tested their effects against liver injury and HCC in cells and in mice. SPIO@AuNP is a non-toxic magnetic resonance (MR)-active contrast agent that can generate heat when irradiated with near-infrared laser. Our results showed that SPIO@AuNPs were successfully transfected into AD-MSCs without compromising either cell viability (P > 0.05) or cell differentiability. In vivo MR imaging and histologic analysis confirmed the active homing of AD-MSCs. Upon laser irradiation, the SPIO@AuNP-loaded AD-MSCs could thermally ablate surrounding HCC tumor cells. SPIO@AuNP-loaded AD-MSCs proved a promising theranostic approach for injured liver and HCC.
机译:肝损伤或肝细胞癌(HCC)的治疗由于缺乏有效的药物输送而受到阻碍。即使借助纳米颗粒或其他合成的递送剂,大部分剂量仍被隔离在网状内皮系统中。作为替代方案,具有归巢至受伤肝脏的能力的脂肪来源的间充质细胞(AD-MSC)可用作治疗试剂的独特载体。治疗试剂必须具有在运输过程中对宿主细胞无毒的能力,并且一旦到达损伤部位就必须及时活化。在这项研究中,我们向AD-MSC加载了超顺磁性氧化铁涂层金纳米颗粒(SPIO @ AuNPs),并测试了它们对细胞和小鼠肝损伤和HCC的作用。 SPIO @ AuNP是一种无毒的磁共振(MR)活性造影剂,当用近红外激光照射时会产生热量。我们的结果表明,SPIO @ AuNPs已成功转染到AD-MSC中,而没有损害细胞活力(P> 0.05)或细胞分化能力。体内MR成像和组织学分析证实了AD-MSC的主动归巢。激光照射后,装载SPIO @ AuNP的AD-MSC可以热消融周围的HCC肿瘤细胞。 SPIO @ AuNP装载的AD-MSC被证明是治疗肝脏和肝癌的有前景的治疗方法。

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