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半乳甘露聚糖武装超顺磁性氧化铁纳米颗粒作为叶酸受体靶向多功能诊疗试剂在癌症治疗中的应用。

Galactomannan armed superparamagnetic iron oxide nanoparticles as a folate receptor targeted multi-functional theranostic agent in the management of cancer.

机构信息

Laboratory of Biopharmaceuticals & Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram 695011, Kerala, India.

Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Thiruvananthapuram 695019, Kerala, India.

出版信息

Int J Biol Macromol. 2022 Oct 31;219:740-753. doi: 10.1016/j.ijbiomac.2022.07.185. Epub 2022 Jul 28.

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) represent a versatile class of theranostics with profound applications in biomedicine. An eco-friendly modification of SPIONs was attempted with a 110 kDa galactomannan (PSP001) isolated from the fruit rind of Punica granatum. The PSP001 appended SPIONs favor unique advantages including tumor-targeted accumulation and improved biocompatibility. The antineoplastic agent methotrexate (MTX) was covalently attached with the galactomannan in the SPIONs to yield PSP-IO NPs that demonstrated a reduction-sensitive drug release kinetics favoring MTX accumulation selectively in the tumor cells. Folate receptor (FR) targeted cancer cell uptake followed by the stimuli-responsive release of the payload favored improved biocompatibility and lack of toxicity in BALB/c mice. Superior tumor reduction capacity with marked survival benefits was observed in Ehrlich ascites carcinoma (EAC) bearing solid tumor mice. Phantom imaging of the carrier (PSP-IO) and the drug-loaded (PSP-IO-MTX NPs) nano-constructs generated an r2 relaxivity of 335.3 mM S and 333.79 mM S respectively indicating the remarkable contrast in magnetic resonance imaging (MRI) which was confirmed in syngraft and xenograft murine models. It is worth mentioning that PSP-IO-MTX NPs with a facile fabrication process offered an affordable nano-theranostic agent for targeted concurrent MR imaging and FR-mediated targeted tumor therapy favoring bed-side applications.

摘要

超顺磁性氧化铁纳米粒子(SPIONs)是一类多功能的治疗诊断一体化试剂,在生物医药领域有广泛的应用。本研究尝试用从石榴果皮中分离得到的 110 kDa 半乳甘露聚糖(PSP001)对 SPIONs 进行绿色环保的修饰。PSP001 修饰的 SPIONs 具有独特的优势,包括肿瘤靶向聚集和提高生物相容性。将抗肿瘤药物甲氨蝶呤(MTX)通过共价键连接到 SPIONs 上的半乳甘露聚糖上,得到 PSP-IO NPs,其表现出还原敏感的药物释放动力学,有利于 MTX 选择性地在肿瘤细胞中积累。叶酸受体(FR)靶向癌细胞摄取,随后响应刺激释放有效载荷,有利于提高生物相容性和缺乏在 BALB/c 小鼠中的毒性。在荷实体瘤的艾氏腹水癌(EAC)小鼠中观察到具有显著生存获益的优越肿瘤缩小能力。载体(PSP-IO)和载药(PSP-IO-MTX NPs)纳米构建体的幻影成像产生了 r2 弛豫率分别为 335.3 mM·s-1 和 333.79 mM·s-1,表明磁共振成像(MRI)有显著的对比,在同种异体和异种移植小鼠模型中得到了证实。值得注意的是,具有简便制备工艺的 PSP-IO-MTX NPs 提供了一种负担得起的靶向同时磁共振成像和 FR 介导的靶向肿瘤治疗的纳米治疗一体化试剂,有利于床边应用。

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