Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China.
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
Biomaterials. 2022 Apr;283:121476. doi: 10.1016/j.biomaterials.2022.121476. Epub 2022 Mar 18.
In view of the fact that pancreatic cancer, called as the king of cancer, is one of the most lethal malignancies, exploring effective technologies for pancreatic cancer diagnosis and therapy remains an appealing yet significantly challenging task. Phototheranostics has recently received considerable attention by virtue of its various distinctive advantages. However, the limited penetration depth, strong oxygen-dependence and high heat shock protein-inhibition of conventional phototheranostic materials severely hamper their overall theranostic efficacy, especially for deep-seated hypoxia tumors, such as pancreatic tumor. In this study, an aggregation-induced emission (AIE)-featured photosensitizer, namely DCTBT, synchronously sharing NIR-II fluorescence imaging (FLI), diminished oxygen-dependent type-I photodynamic therapy (PDT) and high-efficiency photothermal therapy (PTT) functions was subtly constructed by molecular engineering. With the aid of an EGFR-targeting-peptide-modified amphiphilic polymer, the as-prepared DCTBT-loaded liposomes is capable of effectively accumulating at and visualizing pancreatic tumor, as well as significantly suppressing the tumor growth on both subcutaneous and orthotopic PANC-1 tumor mice models. This study thus brings useful insights into designing the next generation of cancer theranostic agents for potential clinical applications.
鉴于胰腺癌被称为“癌中之王”,是最致命的恶性肿瘤之一,探索有效的胰腺癌诊断和治疗技术仍然是一项极具吸引力但极具挑战性的任务。光热治疗最近因其各种独特的优势而受到广泛关注。然而,传统光热治疗材料的有限穿透深度、强氧依赖性和高热休克蛋白抑制严重限制了其整体治疗效果,尤其是对于深部缺氧肿瘤,如胰腺癌。在本研究中,通过分子工程巧妙构建了一种具有聚集诱导发射(AIE)特性的光敏剂,即 DCTBT,同时具有近红外二区荧光成像(FLI)、减弱的氧依赖性 I 型光动力治疗(PDT)和高效光热治疗(PTT)功能。借助 EGFR 靶向肽修饰的两亲聚合物,制备的负载 DCTBT 的脂质体能够有效地在胰腺肿瘤处聚集并进行可视化,并且显著抑制皮下和原位 PANC-1 肿瘤小鼠模型中的肿瘤生长。因此,这项研究为设计用于潜在临床应用的下一代癌症治疗药物提供了有益的见解。