pH-sensitive micelles with charge-reversible property for tumor growth inhibition and anti-metastasis†,Journal of Materials Chemistry B

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pH-sensitive micelles with charge-reversible property for tumor growth inhibition and anti-metastasis†
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2017-12-18 00:00:00 , DOI: 10.1039/c7tb02439h
Yu Sun _{1,

2,

3,

4} , Yuling Bao _{1,

2,

3,

4,

5} , Xue Jiang _{1,

2,

3,

4} , Songwei Tan _{1,

2,

3,

4,

6} , Mingxing Yin _{1,

2,

3,

4,

5} , Conglian Yang _{1,

2,

3,

4} , Liping Zhou _{1,

2,

3,

4} , Zhiping Zhang _{1,

2,

3,

4,

6}

Affiliation

Physical properties, such as surface charge, of nanomedicines play a crucial role in their in vivo behaviors, which could eventually determine the tumor inhibition effect. Although drug delivery systems with positive charge are effective for cell internalization, this property is universally applicable to the lack of selectivity of both tumors and normal tissues, resulting in rapid blood clearance and undesired side effects. By employing charge-reversible strategies, the dilemma can be overcome and enhanced cellular uptake, prolonged circulation time and high biocompatibility can be realized. Here, we constructed Vitamin E-based micelles with charge-reversible property for the delivery of the antineoplastic agent paclitaxel. In the slightly acidic tumor microenvironment, the micelles converted from negative to positive charge due to the cleavage of the pH-sensitive bond, leading to enhanced cellular uptake and subsequently enhanced drug release. The micelles demonstrated improved antitumor efficiency both in vitro and in vivo and improved anti-metastasis effect in 4T1 orthotopic tumor model compared with those of clinically formulated Taxol and non-sensitive micelles. Besides, the micelles showed high biocompatibility and reduced side effects. Overall, these findings highlight that the micelles with charge-reversible property have great potential for cancer therapy in clinic.

中文翻译：

具有电荷可逆性质的pH敏感胶束可抑制肿瘤生长和抗转移†

纳米药物的物理性质（例如表面电荷）在其体内起着至关重要的作用行为，最终可能决定肿瘤抑制作用。尽管带正电荷的药物输送系统对于细胞内化有效，但该特性普遍适用于缺乏肿瘤和正常组织的选择性，从而导致血液快速清除和不良副作用。通过采用电荷可逆策略，可以解决这一难题，并提高细胞摄取，延长循环时间和实现高生物相容性。在这里，我们构建了具有电荷可逆性质的基于维生素E的胶束，用于递送抗肿瘤药紫杉醇。在微酸性的肿瘤微环境中，由于对pH敏感键的裂解，胶束从负电荷转变为正电荷，导致细胞摄取增加，随后药物释放增加。胶束均显示出提高的抗肿瘤效率与临床配制的紫杉醇和非敏感胶束相比，在4T1原位肿瘤模型中具有更高的体外和体内抗转移性。此外，该胶束显示出高的生物相容性并减少了副作用。总体而言，这些发现表明，具有可逆电荷性质的胶束在临床上具有巨大的癌症治疗潜力。

更新日期：2017-12-18

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