Near‐infrared (NIR) fluorescence‐guided surgery is a developing field in precision medicine for cancer treatment. However, traditional NIR fluorescent reagents have limitations including lower sensitivity and specificity for tumor delineation, as well as insufficient photostability and tissue penetration depth. Herein, an improved dual‐targeting lanthanide‐doped NIR‐to‐visible upconversion nanoprobe is constructed for fluorescent imaging of lung cancer. The nanoprobes (UCNP@P‐RGD‐NGR) are synthesized by preparing polydopamine‐coated NaYF₄:Yb/Tm@NaYF₄ upconversion nanoparticles (UCNP) and conjugating them with dual‐targeting peptides RGD10‐NGR9, which are designed to target both integrin αvβ3/αvβ5 and aminopeptidase N receptors on tumor cells. The monodispersed core–shell nanoprobe is rod‐shaped (≈32 nm in minor axis) with ultrathin polydopamine shell (≈2 nm) under transmission electron microscopy. The absorption spectrum and upconversion luminescence properties of the nanoprobes are identified by spectrometry. Toxicity analysis on cellular and animal experiments suggests the nanoprobes are well biocompatible. UCNP@P‐RGD‐NGR can specifically target A549 cancer cells as revealed by competitive cell binding assay and ICP‐MS. Imaging studies in vivo with BALB/c nude mice bearing tumor xenografts demonstrate that UCNP@P‐RGD‐NGR can delineate tumor from surrounding normal tissues with strong upconversion blue–violet luminescence. This dual‐targeting nanoprobe shows great potential for clinical application for NIR fluorescence surgical navigation of lung cancer.

中文翻译：

---

双靶向肽RGD10-NGR9-共轭镧系纳米颗粒@多巴胺作为肺癌体内成像的上转换纳米探针。

近红外（NIR）荧光引导手术是用于治疗癌症的精密医学领域中的一个新兴领域。然而，传统的近红外荧光试剂具有局限性，包括对肿瘤描绘的敏感性和特异性较低，以及光稳定性和组织穿透深度不足。在此，构建了一种改良的双靶掺镧掺杂的近红外到可见光上转换纳米探针，用于肺癌的荧光成像。通过制备聚多巴胺包被的NaYF ₄：Yb / Tm @ NaYF ₄合成纳米探针（UCNP @ P-RGD-NGR）上转换纳米粒子（UCNP）并与双靶向肽RGD10-NGR9结合，后者旨在靶向肿瘤细胞上的整联蛋白αvβ3/αvβ5和氨基肽酶N受体。在透射电子显微镜下，单分散的核壳纳米探针为棒状（短轴≈32nm），具有超薄的聚多巴胺外壳（≈2nm）。纳米探针的吸收光谱和上转换发光性质通过光谱法鉴定。细胞和动物实验的毒性分析表明，纳米探针具有良好的生物相容性。UCNP @ P-RGD-NGR可以特异性地靶向A549癌细胞，这是通过竞争性细胞结合测定和ICP-MS揭示的。用携带肿瘤异种移植物的BALB / c裸鼠进行的体内成像研究表明，UCNP @ P‐RGD‐NGR可以通过强烈的上转换蓝紫色发光将肿瘤与周围正常组织区分开。这种双靶向纳米探针在肺癌的NIR荧光手术导航中显示出巨大的临床应用潜力。