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量子点/生物聚合物/化疗药物的双功能超分子纳米杂化物,用于体外生物成像和杀伤脑癌细胞。

Dual-functional supramolecular nanohybrids of quantum dot/biopolymer/chemotherapeutic drug for bioimaging and killing brain cancer cells in vitro.

机构信息

Center of Nanoscience, Nanotechnology and Innovation - CeNano(2)I, Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais - UFMG, Av. Antônio Carlos, 6627, Belo Horizonte, MG, Brazil.

Center of Nanoscience, Nanotechnology and Innovation - CeNano(2)I, Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais - UFMG, Av. Antônio Carlos, 6627, Belo Horizonte, MG, Brazil; Department of Preventive Veterinary Medicine, Veterinary School, Federal University of Minas Gerais - UFMG, Brazil.

出版信息

Colloids Surf B Biointerfaces. 2019 Dec 1;184:110507. doi: 10.1016/j.colsurfb.2019.110507. Epub 2019 Sep 14.

Abstract

Glioblastoma (GBM) is the utmost aggressive and lethal primary brain cancer, which has a poor prognosis and remains virtually incurable. Nanomedicine with emerging disruptive nanotechnology alternatives, including designed supramolecular nanohybrids has excellent potential as multimodal tools against cancer by combining nanomaterials, biomacromolecules, and drugs. Thus, we developed and constructed for the first time quantum dot-biopolymer-drug nanohybrids based on host-guest chemistry for simultaneous bioimaging, targeting, and anti-cancer drug delivery against GBM cells in vitro. ZnS fluorescent quantum dots (ZnS-QDs) were produced using chemically modified polysaccharide, carboxymethylcellulose (CMC), as water-soluble capping ligand and biofunctional layer via a facile one-step eco-friendly aqueous colloidal process at room temperature and physiological pH. These hybrid inorganic-organic nanocolloids (ZnS@CMC) were electrostatically conjugated with doxorubicin (DOX) anti-cancer drug forming innovative supramolecular complexes (ZnS@CMC-DOX) for amalgamating bioimaging and killing cancer cells. These nanoconjugates were characterized regarding their optical and physicochemical properties combined with morphological and structural features. The cytocompatibility was evaluated by MTT assay using healthy and GBM cells. The results showed that ultra-small ZnS-QDs were expertly produced uniform nanocolloids (average size = 3.6 nm). They demonstrated photoluminescence emission within the visible range of spectra. The cell viability results in vitro showed no cytotoxicity of ZnS@CMC nanohybrids towards both cell types. In summary, the novelty of this research relies on using a nanotheranostic strategy for developing ZnS@CMC-DOX nanohybrids with supramolecular vesicle-like structures. They behaved simultaneously as active fluorescent nanoprobes and nanocarriers with modulated drug release for bioimaging and killing malignant glioma cells proving the high potential for applications in cancer nanomedicine.

摘要

胶质母细胞瘤(GBM)是最具侵袭性和致命性的原发性脑癌,预后不良,几乎无法治愈。新兴的颠覆性纳米技术替代方案的纳米医学,包括设计的超分子纳米杂化物,具有通过结合纳米材料、生物大分子和药物作为对抗癌症的多模式工具的巨大潜力。因此,我们首次开发并构建了基于主客体化学的量子点-生物聚合物-药物纳米杂化物,用于体外同时进行生物成像、靶向和抗癌药物递送针对 GBM 细胞。使用化学修饰的多糖羧甲基纤维素(CMC)作为水溶性封端配体和生物功能层,通过简便的一步法在室温下和生理 pH 值下在水溶液中制备了荧光量子点(ZnS-QDs)胶体。这些杂化无机-有机纳米胶体(ZnS@CMC)通过静电与阿霉素(DOX)抗癌药物共轭,形成创新的超分子复合物(ZnS@CMC-DOX),用于融合生物成像和杀伤癌细胞。这些纳米复合物的光学和物理化学性质以及形态和结构特征进行了表征。通过使用健康细胞和 GBM 细胞的 MTT 测定法评估细胞相容性。结果表明,成功制备了超小的 ZnS-QDs 均匀纳米胶体(平均尺寸为 3.6nm)。它们在可见光谱范围内显示出光致发光发射。体外细胞活力结果表明,ZnS@CMC 纳米杂化物对两种细胞类型均无细胞毒性。总之,本研究的新颖之处在于使用纳米治疗策略开发具有超分子囊泡样结构的 ZnS@CMC-DOX 纳米杂化物。它们同时表现为具有调制药物释放的活性荧光纳米探针和纳米载体,用于生物成像和杀伤恶性神经胶质瘤细胞,证明了在癌症纳米医学中应用的巨大潜力。

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