Synthesis and characterization of CREKA-conjugated iron oxide nanoparticles for hyperthermia applications.

Synthesis and characterization of CREKA-conjugated iron oxide nanoparticles for hyperthermia applications.
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DOI:
10.1016/j.actbio.2014.01.025
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发表时间:
2014-06
期刊:
影响因子:
9.7
通讯作者:
Hilt, J. Zach
Hilt, J. Zach
中科院分区:
工程技术1区
文献类型:
--
作者:
Kruse, Anastasia M.;Meenach, Samantha A.;Anderson, Kimberly W.;Hilt, J. Zach

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当前在癌症治疗应用中全身递送纳米粒子的挑战之一是缺乏有效的肿瘤定位。涂有交联葡聚糖的氧化铁纳米颗粒被肿瘤归巢肽 CREKA 功能化,该肽与肿瘤细胞外基质中的纤维蛋白原复合物结合。这使得这些纳米粒子能够归巢到肿瘤组织。氧化铁纳米颗粒核心允许颗粒在暴露于交变磁场 (AMF) 时加热,而葡聚糖涂层可稳定悬浮液中的颗粒并降低系统的细胞毒性。磁介导热疗 (MMH) 可以加热肿瘤组织,从而提高使用氧化铁纳米粒子的传统癌症治疗的功效。虽然 MMH 提供了局部加热的机会,但该方法目前仍受到颗粒无法渗透到肿瘤组织的限制,即使在有效靶向递送到肿瘤部位后也是如此。所展示的 CREKA 共轭纳米粒子的尺寸、稳定性、加热能力和生物相容性均得到表征。这些颗粒的水合直径为 52 nm,在 PBS 和含有 10% v/v FBS 的介质中稳定至少 12 小时,并且当暴露于 AMF 时,由于平均比吸收率 (SAR) 为 83.5 W/g,会产生足够的热量将溶液温度提高到高温范围 (41 – 45 °C)。细胞毒性研究表明,这些颗粒在低浓度下长时间暴露后具有较低的细胞毒性。使用纤维蛋白原凝血测定来确定 CREKA 缀合颗粒的结合亲和力,该结合亲和力明显大于葡聚糖(仅涂覆氧化铁纳米颗粒)的结合亲和力,证明了该颗粒系统有效归巢于多种肿瘤位置的潜力。最后,与单独使用顺铂或 MMH 治疗相比,体外 MMH 增强了顺铂的作用。
One of the current challenges in the systemic delivery of nanoparticles in cancer therapy applications is the lack of effective tumor localization. Iron oxide nanoparticles coated with crosslinked dextran were functionalized with the tumor homing peptide CREKA, which binds to fibrinogen complexes in the extracellular matrix of tumors. This allows for the homing of these nanoparticles to tumor tissue. The iron oxide nanoparticle core allows for particle heating upon exposure to an alternating magnetic field (AMF) while the dextran coating stabilizes the particles in suspension and decreases the cytotoxicity of the system. Magnetically mediated hyperthermia (MMH) allows for the heating of tumor tissue to increase the efficacy of traditional cancer treatments using the iron oxide nanoparticles. While MMH provides the opportunity for localized heating, this method is currently limited by the lack of particle penetration into tumor tissue, even after effective targeted delivery to the tumor site. The CREKA-conjugated nanoparticles presented were characterized for their size, stability, heating capabilities and biocompatibility. The particles had a hydrated diameter of 52 nm, were stable in PBS and media with 10% v/v FBS over at least twelve hours, and generated enough heat to raise solution temperatures well into the hyperthermia range (41 – 45 °C) when exposed to an AMF due to an average specific absorption rate (SAR) of 83.5 W/g. Cytotoxicity studies demonstrated that the particles have low cytotoxicity over long exposure times at low concentrations. A fibrinogen clotting assay was used to determine the binding affinity of CREKA-conjugated particles, which was significantly greater than the binding affinity of dextran, only coated iron oxide nanoparticles demonstrating the potential for this particle system to effectively home to a variety of tumor locations. Finally, it was shown that in vitro MMH increased the effects of cisplatin compared to cisplatin or MMH treatments alone.
用于基于热疗的治疗和受控药物递送的磁纳米材料。
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