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用于胶质母细胞瘤应用的肿瘤靶向金纳米颗粒的优化

Optimization of Tumor Targeting Gold Nanoparticles for Glioblastoma Applications.

作者信息

Allen Nicholas C, Chauhan Rajat, Bates Paula J, O'Toole Martin G

机构信息

Department of Bioengineering, University of Louisville, Louisville, KY 40292, USA.

Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.

出版信息

Nanomaterials (Basel). 2022 Nov 2;12(21):3869. doi: 10.3390/nano12213869.

Abstract

Glioblastoma brain tumors represent an aggressive form of gliomas that is hallmarked by being extremely invasive and aggressive due to intra and inter-tumoral heterogeneity. This complex tumor microenvironment makes even the newer advancements in glioblastoma treatment less effective long term. In developing newer treatment technologies against glioblastoma, one should tailor the treatment to the tumor microenvironment, thus allowing for a more robust and sustained anti-glioblastoma effect. Here, we present a novel gold nanoparticle therapy explicitly designed for bioactivity against glioblastoma representing U87MG cell lines. We employ standard conjugation techniques to create oligonucleotide-coated gold nanoparticles exhibiting strong anti-glioblastoma behavior and optimize their design to maximize bioactivity against glioblastoma. Resulting nanotherapies are therapy specific and show upwards of 75% inhibition in metabolic and proliferative activity with stark effects on cellular morphology. Ultimately, these gold nanotherapies are a good base for designing more multi-targeted approaches to fighting against glioblastoma.

摘要

胶质母细胞瘤是一种侵袭性很强的胶质瘤,其特征是由于肿瘤内部和肿瘤之间的异质性而具有极强的侵袭性。这种复杂的肿瘤微环境使得即使是胶质母细胞瘤治疗方面的最新进展,从长期来看效果也不太理想。在开发针对胶质母细胞瘤的新型治疗技术时,应该根据肿瘤微环境来定制治疗方案,从而实现更强有力且持久的抗胶质母细胞瘤效果。在此,我们展示了一种专门设计用于对代表U87MG细胞系的胶质母细胞瘤具有生物活性的新型金纳米粒子疗法。我们采用标准偶联技术来制备具有强抗胶质母细胞瘤行为的寡核苷酸包被金纳米粒子,并对其设计进行优化,以最大限度地提高对胶质母细胞瘤的生物活性。所得的纳米疗法具有治疗特异性,对代谢和增殖活性的抑制率高达75%以上,对细胞形态有显著影响。最终,这些金纳米疗法是设计更多针对胶质母细胞瘤的多靶点治疗方法的良好基础。

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