Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, Aachen 52074, Germany.
Anal Chem. 2021 Sep 7;93(35):12103-12115. doi: 10.1021/acs.analchem.1c02625. Epub 2021 Aug 24.
Despite several attempts, incorporating biological detection that supplies necessary biological information into therapeutic nanotheranostics for hypoxic tumor treatments is considered to be in its infancy. It is therefore imperative to consolidate biological detection and desirable phototherapy into a single nanosystem for maximizing theranostic advantages. Herein, we develop a versatile nanoprobe through combined fluorescence resonance energy transfer (FRET) and oxygen-augmenting strategy, namely APT, which enables glycosylation detection, O self-sufficiency, and collaborative phototherapy. Such APT nanoprobes were constructed by depositing platinum onto gold nano-bipyramids (Au NBPs), linking FITC fluorophore-labeled AS1411 aptamers for introducing FRET donors, and by conjugating G-quadruplex intercalated with TMPyP4 to their surfaces the SH-DNA chain. By installing FRET acceptors on the glycan of targeted EpCAM glycoprotein using the metabolic glycan labeling and click chemistry, FRET signals appear on the cancerous cell membranes, not normal cells, when donors and acceptors are within an appropriate distance. This actualizes protein-specific glycosylation visualization while revealing glycan-based changes correlated with tumor progression. Interestingly, the deposited platinum scavenges excessive HO as artificial nanoenzymes to transform O that alleviates tumor hypoxia and simultaneously elevates singlet oxygen (O) for inducing cancer cell apoptosis. Notably, the significant hyperthermia devastation was elicited APT nanoprobes with phenomenal photothermal therapy (PTT) efficiency (71.8%) for thermally ablating cancer cells, resulting in synergistically enhanced photodynamic-hyperthermia therapy. Consequently, APT nanoprobes nearly actualized thorough tumor ablation while demonstrating highly curative biosafety. This work offers a new paradigm to rationally explore a combined FRET and oxygen-augmenting strategy with a focus on nanotheranostics for hypoxic tumor elimination.
尽管已经进行了多次尝试，但将提供必要生物学信息的生物检测纳入治疗性纳米治疗学以治疗缺氧肿瘤仍处于起步阶段。因此，当务之急是将生物检测和理想的光疗整合到单个纳米系统中，以最大限度地发挥治疗优势。在这里，我们通过结合荧光共振能量转移（FRET）和增氧策略开发了一种多功能纳米探针，即 APT，它能够进行糖基化检测、O 自给自足和协同光疗。这种 APT 纳米探针是通过在金纳米双锥体（Au NBPs）上沉积铂、连接用于引入 FRET 供体的 FITC 荧光团标记的 AS1411 适体以及在其表面上缀合与 TMPyP4 相互作用的 G-四链体来构建的。通过使用代谢糖基化标记和点击化学将 FRET 受体安装在靶向 EpCAM 糖蛋白的糖基上，当供体和受体处于适当距离时，FRET 信号出现在癌细胞膜上，而不是正常细胞上。这实现了蛋白质特异性糖基化可视化，同时揭示了与肿瘤进展相关的糖基变化。有趣的是，沉积的铂作为人工纳米酶来清除过量的 HO 以转化 O，从而减轻肿瘤缺氧并同时提高用于诱导癌细胞凋亡的单线态氧（O）。值得注意的是，由于具有出色的光热治疗（PTT）效率（71.8%），APT 纳米探针引发了显著的高热破坏，从而协同增强了光动力-热疗。因此，APT 纳米探针几乎实现了对肿瘤的彻底消融，同时表现出高度有效的生物安全性。这项工作为合理探索基于纳米治疗学的 FRET 和增氧策略提供了一个新范例，以消除缺氧肿瘤。
