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用于癌症治疗的基于pH敏感和氧化还原响应性聚(四乙二醇)纳米颗粒的平台。

pH-sensitive and redox-responsive poly(tetraethylene glycol) nanoparticle-based platform for cancer treatment.

作者信息

Sun Qian, Kong Nuocheng, Zhao Hanqing, Zhang Xianwen, Tao Qimeng, Jiang Hao, Xuan Aili, Li Xianming

机构信息

Jinan University, Guangzhou 510632, Guangdong, People's Republic of China.

Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui, People's Republic of China.

出版信息

Nanotechnology. 2024 Sep 27;35(49). doi: 10.1088/1361-6528/ad7c54.

DOI:10.1088/1361-6528/ad7c54
PMID:39293467
Abstract

Effective drug delivery with precise tumour targeting is crucial for cancer treatment. To address the challenges posed by the specificity and complexity of the tumour microenvironment, we developed a poly(tetraethylene glycol)-based disulfide nanoparticle (NP) platform and explored its potential in cancer treatment, focusing on drug loading and controlled release performance. Poly(tetraethylene glycol) NPs were characterised using nuclear magnetic resonance spectroscopy, mass spectrometry, and ultraviolet-visible spectroscopy. Additionally, we evaluated physicochemical properties, including dynamic light scattering, zeta potential analysis, drug loading capacity (DLC), and drug loading efficiency (DLE). The impact of NPs on the mouse colorectal cancer cell line (CT26) and NIH3T3 cells was assessed using a cytotoxicity assay, live/dead staining assay, flow cytometry, and confocal fluorescence microscopy. The experimental results align with the expected chemical structure and physicochemical properties of poly(tetraethylene glycol) NPs. These NPs exhibit high DLE (78.7%) and DLC (12%), with minimal changes in particle size over time in different media.experiments revealed that the NPs can induce significant cytotoxicity and apoptosis in CT26 cells. Cellular uptake notably increases with increasing concentration and exposure time. The confocal microscopic analysis confirmed the effective distribution and accumulation of NPs within cells. In conclusion, poly(tetraethylene glycol) NPs hold promise for improving drug-delivery efficiency, offering potential advancements in cancer treatment.

摘要

实现精确的肿瘤靶向给药对癌症治疗至关重要。为应对肿瘤微环境的特异性和复杂性带来的挑战,我们开发了一种基于聚(四乙二醇)的二硫键纳米颗粒(NP)平台,并探索了其在癌症治疗中的潜力,重点关注药物负载和控释性能。使用核磁共振光谱、质谱和紫外可见光谱对聚(四乙二醇)纳米颗粒进行了表征。此外,我们评估了其物理化学性质,包括动态光散射、zeta电位分析、药物负载量(DLC)和药物负载效率(DLE)。使用细胞毒性试验、活/死染色试验、流式细胞术和共聚焦荧光显微镜评估了纳米颗粒对小鼠结肠癌细胞系(CT26)和NIH3T3细胞的影响。实验结果与聚(四乙二醇)纳米颗粒预期的化学结构和物理化学性质相符。这些纳米颗粒表现出高DLE(78.7%)和DLC(12%),在不同介质中随时间粒径变化最小。实验表明,纳米颗粒可在CT26细胞中诱导显著的细胞毒性和凋亡。细胞摄取量随浓度和暴露时间的增加而显著增加。共聚焦显微镜分析证实了纳米颗粒在细胞内的有效分布和积累。总之,聚(四乙二醇)纳米颗粒有望提高药物递送效率,为癌症治疗带来潜在进展。

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