Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases,Journal of the American Chemical Society

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Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2024-02-08 , DOI: 10.1021/jacs.3c11666
Jingqin Chen ₁ , Rui Chen _{1,

2,

3,

4} , Calvin V Chau ₅ , Adam C Sedgwick ₆ , Qiang Xue ₁ , Tao Chen ₁ , Silue Zeng _{1,

2} , Ningbo Chen _{1,

7} , Kenneth K Y Wong ₇ , Liang Song ₁ , Yaguang Ren ₁ , Jian Yang _{2,

3} , Jonathan L Sessler ₅ , Chengbo Liu ₁

Affiliation

Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an α_vβ₃-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.

中文翻译：

基于环[8]吡咯的靶向 NIR-II 光声断层扫描探针用于抑制原位胰腺肿瘤生长和腹内转移

胰腺癌具有高度致命性。迫切需要新的诊断和治疗方式。我们在这里报道了一种扩展的卟啉，环[8]吡咯（CP），在第二近红外窗口（NIR-II）内具有高消光系数（89.16 L/g·cm），可以用α _v配制β ₃特异性靶向肽，环精氨酸-甘氨酸-天冬氨酸 (cRGD)，形成 cRGD-CP 纳米颗粒 (cRGD-CPNPs)，具有前景广阔的 NIR-II 光热 (PT) 治疗和光声 (PA) 成像特性。使用环形阵列 PA 断层扫描系统的研究，加上对缺乏靶向元件 (CPNP) 的对照纳米粒子 (CPNP) 的分析，表明 cRGD 缀合促进了 NP 通过肿瘤周围的异常血管输送到实体瘤核心。正如免疫荧光研究所证实的那样，这在皮下和原位胰腺肿瘤小鼠模型中都被证明是正确的。与 NIR-II 激光光照射相结合，cRGD-CPNP 通过 PTT 在体外和体内提供接近基线的肿瘤生长抑制。值得注意的是，发现本发明的 cRGD-CPNP 和光照射的组合可以抑制原位胰腺肿瘤小鼠模型的腹内转移。根据 PA 断层扫描、血液分析和 H&E 染色推断，cRGD-CPNP 还表现出良好的生物安全性。因此，它们有望用于胰腺癌的 PA 成像和 PT 联合治疗。

更新日期：2024-02-08

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