Allan H. Conney Laboratory for Anticancer Research, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.
Allan H. Conney Laboratory for Anticancer Research, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.
J Control Release. 2024 Apr;368:650-662. doi: 10.1016/j.jconrel.2024.03.020. Epub 2024 Mar 18.
Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.
脑深部的胶质母细胞瘤（GBM）比其他肿瘤更难诊断和治疗。这些挑战阻碍了将可靠诊断与靶向治疗相结合的高影响力治疗方法的发展。在这里，通过“扩展共轭和分子转子”策略，开发了具有近红外二区（NIR-II）吸附和聚集诱导发射（AIE）的有效菁染料（IRLy），用于深部原位 GBM 的多模态成像和光疗。通过合理的分子转子修饰成功合成了 IRLy，具有更强的穿透力、更高的信噪比和高达约 60%的高光热转换效率（PCE），可实现高效的 NIR-II 光响应。进一步制备了多功能纳米颗粒（Tf-IRLy NPs），通过转铁蛋白（Tf）作为靶向配体来穿过血脑屏障（BBB）。Tf-IRLy NPs 在体外和体内均表现出良好的生物安全性和对 GBM 的肿瘤富集，从而实现了准确、高效和低侵入性的 NIR-II 多模态成像和光热治疗。这种多功能的 Tf-IRLy 纳米系统可为高效、精确和低侵入性的多协同脑靶向光治疗提供参考。此外，“扩展共轭和分子转子”策略可用于指导其他光热剂的设计。
