Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou First People's Hospital, Cancer Center of Zhejiang University, Hangzhou, 310006, China.
Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Adv Mater. 2024 Sep;36(36):e2405275. doi: 10.1002/adma.202405275. Epub 2024 Jul 27.
The development of minimally invasive surgery has greatly advanced precision tumor surgery, but sometime suffers from restricted visualization of the surgical field, especially during the removal of abdominal tumors. A 3-D inspection of tumors could be achieved by intravenously injecting tumor-selective fluorescent probes, whereas most of which are unable to instantly distinguish tumors via in situ spraying, which is urgently needed in the process of surgery in a convenient manner. In this study, this work has designed an injectable and sprayable fluorescent nanoprobe, termed Poly-g-BAT, to realize rapid tumor imaging in freshly dissected human colorectal tumors and animal models. Mechanistically, the incorporation of γ-glutamyl group facilitates the rapid internalization of Poly-g-BAT, and these internalized nanoprobes can be subsequently activated by intracellular NAD(P)H: quinone oxidoreductase-1 to release near-infrared fluorophores. As a result, Poly-g-BAT can achieve a superior tumor-to-normal ratio (TNR) up to 12.3 and enable a fast visualization (3 min after in situ spraying) of tumor boundaries in the xenograft tumor models, Apc mice models and fresh human tumor tissues. In addition, Poly-g-BAT is capable of identifying minimal premalignant lesions via intravenous injection.
微创手术的发展极大地推动了精准肿瘤手术，但有时会受到手术视野受限的影响，特别是在切除腹部肿瘤时。可以通过静脉注射肿瘤选择性荧光探针来实现肿瘤的 3D 检查，但大多数探针无法通过原位喷洒即时区分肿瘤，这在手术过程中是急需的一种便捷方式。在本研究中，我们设计了一种可注射和可喷洒的荧光纳米探针，称为 Poly-g-BAT，以实现对新鲜剖取的人结直肠肿瘤和动物模型中的快速肿瘤成像。从机制上讲，γ-谷氨酰基的掺入有助于 Poly-g-BAT 的快速内化，这些内化的纳米探针随后可以被细胞内 NAD(P)H:醌氧化还原酶-1 激活，释放出近红外荧光团。结果，Poly-g-BAT 可以实现高达 12.3 的肿瘤与正常组织的高对比率（TNR），并能够在异种移植肿瘤模型、Apc 小鼠模型和新鲜人肿瘤组织中快速可视化（原位喷洒后 3 分钟）肿瘤边界。此外，Poly-g-BAT 还能够通过静脉注射识别最小的癌前病变。
