Bioactive Natural Small Molecule-Tuned Coassembly of Photosensitive Drugs for Highly Efficient Synergistic and Enhanced Type I Photochemotherapy
Bioactive Natural Small Molecule-Tuned Coassembly of Photosensitive Drugs for Highly Efficient Synergistic and Enhanced Type I Photochemotherapy
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DOI：
10.1021/acsami.0c13164
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发表时间：
2020-09-30
影响因子：
9.5
通讯作者：
Yang, Xin
中科院分区：
文献类型：
--
作者：
Cheng, Jianjun;Zhao, Haitian;Yang, Xin
自组装天然小分子(NSM)具有良好的抗癌活性，作为一种无需结构修饰的新型给药平台，在生物医学领域的应用越来越受到人们的关注。然而，由于缺乏对NSM作为药物载体的认识和实用性，限制了其目前在生物医学上的应用。在这里，我们通过绿色和简便的超分子共组装策略，报道和开发了一系列无载体的萜类天然小分子介导的共组装光敏药物，用于增强和协同化疗/光动力学治疗。在筛选了17个萜类NSM后，我们鉴定了11个化合物，它们可以形成可调节药物大小的NSM-Ce6纳米粒子。对具有代表性的白桦脂酸(BC)介导的纳米共组装(BC-Ce6 NPs)的分析揭示了共组装策略的高效性，并突出了NSM作为新型药物传递平台的巨大潜力。通过分子动力学模拟和理论计算，我们解释了共组装过程的奥秘，表明BC二聚体单元的线性共面排列是形成棒状或球形形态的主要原因。同时，我们证明了单重态和三重态之间能量差的减小(Delta E-ST)通过I型光反应机制促进了中心点OH的生成，从而促进了有效的活性氧物种的生成。组装的纳米药物显示出多种良好的治疗特性，确保了高效肿瘤消融的93.6%的显著增强、协同和安全的组合抗癌效果。这项工作不仅拓展了天然生物可降解材料广泛应用于生物领域的可能性，而且为构建NSM介导的用于精确治疗的纳米协同组装体提供了新的视角。
Self-assembling natural small molecules (NSMs) with favorable anticancer activity are of increasing interest as novel drug delivery platforms without structural modification for biomedical applications. However, a lack of knowledge and practicability of NSMs as drug carriers limited their current biomedical application. Here, via a green and facile supramolecular coassembly strategy, we report and develop a series of carrier-free terpenoid natural small molecule-mediated coassembled photosensitive drugs for enhanced and synergistic chemo/photodynamic therapy. After screening 17 terpenoid NSMs, we identified 11 compounds that could form coassembled NSMs-Ce6 NPs with regulatable drug sizes. Analysis of the representative betulonic acid (BC)-mediated nano-coassemblies (BC-Ce6 NPs) reveals the high efficiency of the coassembly strategy and highlights the tremendous potential of NSMs as novel drug delivery platforms. Through molecular dynamics simulation and theoretical calculations, we elucidate the mystery of the coassembly process, indicating that the linear coplanar arrangement of BC dimeric units is primarily responsible for the formation of rod-like or spherical morphology. Meanwhile, we demonstrated that the reduced energy gap between the singlet and triplet excited states (Delta E-ST) facilitates efficient reactive oxygen species generation by promoting center dot OH generation via a type I photoreaction mechanism. The assembled nanodrugs exhibit multiple favorable therapeutic features, ensuring a remarkably enhanced, synergistic, and secure combinatorial anticancer efficacy of 93.6% with highly efficient tumor ablation. This work not only expands the possibility of natural biodegradable materials for wide biological applications but also provides a new perspective for the construction of NSM-mediated nano-coassemblies for precision therapy.