State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, P. R. China.
Key Lab of Organic Optoelectronics & Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing, 100084, P. R. China.
Small. 2023 May;19(19):e2300203. doi: 10.1002/smll.202300203. Epub 2023 Feb 12.
Extensive efforts have been devoted to the design of organic photothermal agents (PTAs) that absorb in the second near-infrared (NIR-II) bio-window, which can provide deeper tissue penetration that is significant for phototheranostics of lethal brain tumors. Herein, the first example of NIR-II-absorbing small organic molecule (N1) derived from perylene monoamide (PMI) and its bio-application after nano-encapsulation of N1 to function as a nano-agent for phototheranostics of deep orthotopic glioblastoma (GBM) is reported. By adopting a dual modification strategy of introducing a donor-acceptor unit and extending π-conjugation, the obtained N1 can absorb in 1000-1400 nm region and exhibit high photothermal conversation due to the apparent intramolecular charge transfer (ICT). A choline analogue, 2-methacryloyloxyethyl phosphorylcholine, capable of interacting specifically with receptors on the surface of the blood-brain barrier (BBB), is used to fabricate the amphiphilic copolymer for the nano-encapsulation of N1. The obtained nanoparticles demonstrate efficient BBB-crossing due to the receptor-mediated transcytosis as well as the small nanoparticle size of approximately 26 nm. The prepared nanoparticles exhibit excellent photoacoustic imaging and significant growth inhibition of deep orthotopic GBM. The current study demonstrates the enormous potential of PMI-based NIR-II PTAs and provides an efficient phototheranostic paradigm for deep orthotopic GBM.
研究人员致力于设计能在近红外二区（NIR-II）生物窗口吸收的有机光热剂（PTAs），这能为致死性脑肿瘤的光疗提供更深的组织穿透性。在此，报道了首例源自苝单酰胺（PMI）的 NIR-II 吸收小分子（N1）及其在纳米封装后的生物应用，N1 被纳米封装后可作为深部原位神经胶质瘤（GBM）光疗的纳米剂。通过采用引入给体-受体单元和扩展π共轭的双重修饰策略，得到的 N1 在 1000-1400nm 区域内吸收，并由于明显的分子内电荷转移（ICT）而表现出高的光热转换效率。采用 2-（甲基丙烯酰氧）乙基磷酸胆碱，一种能与血脑屏障（BBB）表面受体特异性相互作用的胆碱类似物，用于制备用于 N1 纳米封装的两亲性共聚物。所得纳米粒子由于受体介导的转胞作用以及约 26nm 的小纳米粒子尺寸，表现出有效的 BBB 穿越能力。所制备的纳米粒子表现出优异的光声成像和对深部原位 GBM 的显著抑制生长效果。本研究展示了基于 PMI 的近红外二区 PTAs 的巨大潜力，并为深部原位 GBM 提供了一种有效的光疗范例。
