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通过靶向神经母细胞瘤多涎酸的纳米导弹进行光热治疗。

Photothermal Therapy of Neuroblastoma via Polysialic Acid-Targeting Nanomissiles.

机构信息

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China.

出版信息

Small. 2022 Nov;18(46):e2201671. doi: 10.1002/smll.202201671. Epub 2022 Sep 26.

Abstract

Exploring new targets and developing novel targeted therapies are urgently needed for neuroblastoma therapy. Polysialic acid (polySia), a linear homopolymer of sialic acid units that correlates well with tumor progression and poor prognosis, has emerged as a potential target for neuroblastoma. However, the lack of polySia-specific binding reagents has severely limited the development of polySia-targeting therapeutics for neuroblastoma. Herein, the construction of polySia-targeting nanomissiles via molecular imprinting for the photothermal therapy of neuroblastoma is reported. Oligosialic acid (oligoSia) containing 3-4 units is considered as a characteristic structure for the recognition of polySia, while oligoSia containing 4-7 units digested from polySia is employed as the template. Via boronate-affinity controllable oriented surface imprinting, oligoSia-imprinted nanoparticles (oSia-MIP) are prepared. The oSia-MIP allows for specifically recognizing polySia and targeting polySia overexpressed neuroblastoma cells in vitro and in vivo. oSia-MIP loaded with indocyanine green is prepared and experimentally demonstrated to be a potent targeted photothermal therapeutic for neuroblastoma. Equipping the core substrate with functional entities, the developed polySia targeting nanoplatform can be accommodated to various therapeutic modalities, holding great promise for neuroblastoma targeted therapy.

摘要

探索新的靶点并开发新的靶向治疗方法对于神经母细胞瘤的治疗至关重要。多涎酸(polySia)是一种与肿瘤进展和预后不良密切相关的唾液酸单元的线性同聚物,已成为神经母细胞瘤的一个潜在靶点。然而,缺乏多涎酸特异性结合试剂严重限制了神经母细胞瘤多涎酸靶向治疗药物的发展。本文报道了通过分子印迹构建用于神经母细胞瘤光热治疗的多涎酸靶向纳米导弹。含有 3-4 个单元的寡涎酸(oligoSia)被认为是识别多涎酸的特征结构,而从多涎酸中消化得到的含有 4-7 个单元的寡涎酸则被用作模板。通过硼酸亲和可控定向表面印迹,制备了寡涎酸印迹纳米颗粒(oSia-MIP)。oSia-MIP 能够特异性识别多涎酸,并在体外和体内靶向表达多涎酸的神经母细胞瘤细胞。制备了装载吲哚菁绿的 oSia-MIP,并进行了实验验证,结果表明其是一种有效的针对神经母细胞瘤的靶向光热治疗试剂。通过在核心基质上配备功能实体,开发的多涎酸靶向纳米平台可以适应各种治疗模式,为神经母细胞瘤的靶向治疗带来了广阔的前景。

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