Abstract

Aims

To construct a self-assembly supramolecular drug delivery system (DDS) to co-deliver chlorin e6 (Ce6) and tripeptide tyroseroleutide (YSL) and evaluate the anti-tumour effects.

Methods

A supramolecular DDS was constructed via self-assembly of Ce6 and YSL based on π-π stacking and hydrogen-bond interaction. The size, morphology, stability, in vitro drug release, cellular uptake, cytotoxicity, pharmacokinetics analysis and pharmacodynamics analysis were respectively studied.

Results

Ce6-YSL nanoparticles with a uniform size of 75 ± 3.5 nm (PDI = 0.128) and monodispersed spherical morphology were constructed. The nanoparticles exhibited good stability with zeta potential −21.2 ± 1.73 mV. Under the weak acidic conditions, the accumulative drug release was 82.8% (w/w) (pH = 6.0) and 91.5% (w/w) (pH = 5.0), respectively, indicating that nanoparticles performed smart responsive properties and achieved controlled release characteristics in acidic tumour microenvironment. In addition, nanoparticles could easily enter the tumour cells and induce ROS production and inhibit cell proliferation in SMMCC-7721 cells with IC₅₀ value 3.4 ± 0.023 μg/mL under laser irradiation. Furthermore, the nanoparticles could retain a much higher blood concentration in vivo and displayed excellent antitumor effect in tumour-bearing mice, showing no influence on body weight.

Conclusions

This self-assembly supramolecular DDS can be used for combination of photodynamic therapy and chemotherapy in future research.

中文翻译：

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用于光动力疗法和化疗联合的自组装超分子药物递送系统

 抽象的

 目标

构建自组装超分子药物递送系统（DDS）共同递送二氢卟酚e6（Ce6）和三肽酪氨酸（YSL）并评估其抗肿瘤作用。

 方法

基于π-π堆积和氢键相互作用，通过Ce6和YSL自组装构建了超分子DDS。分别对其大小、形态、稳定性、体外药物释放、细胞摄取、细胞毒性、药代动力学分析和药效学分析进行了研究。

 结果

构建了尺寸均匀为 75 ± 3.5 nm（PDI = 0.128）和单分散球形形态的 Ce6-YSL 纳米颗粒。纳米粒子表现出良好的稳定性，zeta 电位为-21.2 ± 1.73 mV。在弱酸性条件下，累积药物释放率分别为82.8%（w/w）（pH = 6.0）和91.5%（w/w）（pH = 5.0），表明纳米粒子表现出智能响应特性并实现了控释。酸性肿瘤微环境的特点。此外，在激光照射下，纳米颗粒可以很容易地进入肿瘤细胞，诱导ROS产生并抑制SMMCC-7721细胞的细胞增殖，IC ₅₀值为3.4 ± 0.023 μg/mL。此外，纳米粒子在体内可以保留更高的血液浓度，并且在荷瘤小鼠中表现出优异的抗肿瘤效果，且对体重没有影响。

 结论

这种自组装超分子DDS可在未来的研究中用于光动力疗法和化疗的结合。