Simple and Multifunctional Natural Self-Assembled Sterols with Anticancer Activity-Mediated Supramolecular Photosensitizers for Enhanced Antitumor Photodynamic Therapy
Simple and Multifunctional Natural Self-Assembled Sterols with Anticancer Activity-Mediated Supramolecular Photosensitizers for Enhanced Antitumor Photodynamic Therapy
复制标题
简单且多功能的天然自组装甾醇具有抗癌活性介导的超分子光敏剂，用于增强抗肿瘤光动力治疗
DOI：
10.1021/acsami.9b07404
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发表时间：
2019-08-21
影响因子：
9.5
通讯作者：
Yang, Xin
中科院分区：
文献类型：
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作者：
Cheng, Jianjun;Zhao, Haitian;Yang, Xin
基于纳米药物递送或联合治疗的超分子光敏剂已被提出作为一种有前途的癌症治疗策略。本研究筛选并开发了一系列具有自组装能力、抗癌活性、生物相容性和生物降解性的多功能单组分、载体型天然小分子甾醇（麦角甾醇、β-谷甾醇和豆甾醇），用于光敏剂二氢卟酚e6（Ce 6）的光动力学联合抗肿瘤治疗。所得到的麦角甾醇-Ce 6纳米药物（Ergo-Ce 6 NPs）通过促进I型光反应而增强活性氧（ROS）的产生，而Ce 6主要通过分子间π-π堆积和疏水相互作用以单体状态存在于组装的Ergo-Ce 6 NPs中。此外，由于改善的水溶性和稳定性以及更高的细胞间ROS产生，Ergo-Ce 6 NPs显示出显著的体外光毒性，在相当低的Ce 6剂量（1 μ g/mL）下，对4 T1和MCF-7癌细胞的细胞抑制率分别为约73%和92%。此外，Ergo NPs优异的肿瘤靶向能力和延长的血液循环确保了Ergo-Ce 6 NPs的快速肿瘤积聚，导致显著增强的体内抗癌效率为86.4%，高于Ergo NPs（51.0%）或Ce 6 PDT单独的抗癌能力（59.5%）。此外，所得纳米药物具有更好的生物相容性和生物降解性以及低的体内毒性，所有这些都确保了安全的肿瘤治疗。本研究为开发更多天然自组装生物小分子纳米材料，用于制备新型医用光敏剂提供了一个很好的前景。
Supramolecular photosensitizers based on nanosized drug delivery or combination therapy have been proposed as a promising strategy for cancer treatment. Herein, we screen and develop a series of multifunctional single-component, carrier-based, natural small-molecule sterols (ergosterol, beta-sitosterol, and stigmasterol) that simultaneously possess self-assembly ability, anticancer activity, and better biocompatibility and biodegradability to deliver photosensitizer chlorin e6 (Ce6) for significantly combined and safe antitumor photodynamic therapy. The resultant ergosterol-Ce6 nanodrugs (Ergo-Ce6 NPs) have enhanced reactive oxygen species (ROS) generation by promoting type I photoreactions, while Ce6 mainly exists in the monomer state in assembled Ergo-Ce6 NPs via intermolecular pi-pi stacking and hydrophobic interactions. In addition, with the improved water solubility and stability and higher intercellular ROS generation, Ergo-Ce6 NPs show remarkably in vitro phototoxicity with approximately 73% and 92% cell inhibition ratios to 4T1 and MCF-7 cancer cells at a rather low dosage of Ce6 (1 mu g/mL), respectively. Moreover, the excellent tumor targeting ability of Ergo NPs and prolonged blood circulation ensure a quick tumor accumulation of Ergo-Ce6 NPs, resulting in a significantly enhanced in vivo anticancer efficiency of 86.4%, higher than that of the anticancer ability of Ergo NPs (51.0%) or Ce6 PDT alone (59.5%). Furthermore, the resulting nanodrugs have better biocompatibility and biodegradability and low in vivo toxicity, and all of which ensure a safe tumor therapy. This study provides a promising perspective to develop more natural self-assembled biological small-molecule nanomaterials for the fabrication of novel medicinal photosensitizers for clinical application in the future.