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首页> 外文期刊>ACS applied materials & interfaces >Simple and Multifunctional Natural Self-Assembled Sterols with Anticancer Activity-Mediated Supramolecular Photosensitizers for Enhanced Antitumor Photodynamic Therapy
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Simple and Multifunctional Natural Self-Assembled Sterols with Anticancer Activity-Mediated Supramolecular Photosensitizers for Enhanced Antitumor Photodynamic Therapy

机译：简单和多功能自然自组装甾醇，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

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摘要

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.
机译：已经提出了基于纳米化药物递送或组合治疗的超分子光敏剂作为癌症治疗的有希望的策略。在此，我们筛选并开发一系列多功能单组分，载体的天然小分子甾醇（Ergosterol，Beta-sitosterol和Stigmasterol），其同时具有自组装能力，抗癌活性和更好的生物相容性和生物补充剂为显着组合和安全的抗肿瘤光动力疗法提供光敏剂氯蛋白E6（CE6）。由此得到的Ergosterol-Ce6纳米载体（ERGO-CE6 NPS）通过促进I型光电反应具有增强的活性氧物质（ROS），而CE6主要存在于通过分子间PI-PI堆叠和疏水相互作用组装的ERGO-CE6 NP中的单体状态。此外，随着水溶性和稳定性和更高的细胞间ROS产生，ERGO-CE6 NPS在体外光炎，在CE6的相当低的剂量下，具有约73％和92％的细胞抑制比至4T1和MCF-7癌细胞的体外光毒性。 （1μg/ ml）。此外，ERGO NPS和延长血液循环的优异肿瘤靶向能力确保了ERGO-CE6 NPS的快速肿瘤积累，导致体内抗癌效率显着增强86.4％，高于ERGO NPS的抗癌能力（51.0单独的％）或CE6 PDT（59.5％）。此外，所得的纳米树脂具有更好的生物相容性和生物降解性，并且体内毒性低，并且所有这些都确保了安全的肿瘤疗法。本研究提供了有希望的观点，可开发更自然的自组装生物小分子纳米材料，用于制造未来临床应用的新型药用光敏。

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