Abstract：
Early and accurate cancer diagnosis is crucial for improving patient survival rates. Luminescent nanoparticles have emerged as a promising tool in fluorescence bioimaging for cancer diagnosis. To enhance diagnostic accuracy, ligands promoting endocytosis into cancer cells are commonly incorporated onto nanoparticle surfaces. Folic acid (FA) is one such ligand, known to specifically bind to folate receptors (FR) overexpressed in various cancer cells such as cervical and ovarian carcinoma. Therefore, surface modification of luminescent nanoparticles with FA can enhance both luminescence efficiency and diagnostic accuracy. In this study, luminescent europium-doped hydroxyapatite (EuHAp) nanocrystals were prepared via hydrothermal method and subsequently modified with (3-Aminopropyl)triethoxysilane (APTES) followed by FA to target FR-positive human cervical adenocarcinoma cell line (HeLa) cells. The sequential grafting of APTES and then FA formed a robust covalent linkage between the nanocrystals and FA. Rod-shaped FA-modified EuHAp nanocrystals, approximately 100 nm in size, exhibited emission peaks at 589, 615, and 650 nm upon excitation at 397 nm. Despite a reduction in photoluminescence intensity following FA modification, fluorescence microscopy revealed a remarkable 120-fold increase in intensity compared to unmodified EuHAp, attributed to the enhanced uptake of FA-modified EuHAp. Additionally, confocal microscope observations confirmed the specificity and the internalization of FA-modified EuHAp nanocrystals in HeLa cells. In conclusion, the modification of EuHAp nanocrystals with FA presents a promising strategy to enhance the diagnostic potential of cancer bioimaging probes.
摘要：
早期和准确的癌症诊断对于提高患者生存率至关重要。发光纳米颗粒已经成为用于癌症诊断的荧光生物成像中的有前途的工具。为了提高诊断的准确性，促进内吞作用进入癌细胞的配体通常结合到纳米颗粒表面上。叶酸(FA)是一种这样的配体，已知特异性结合在各种癌细胞如宫颈癌和卵巢癌中过度表达的叶酸受体(FR)。因此,用FA对发光纳米粒子进行表面修饰可以提高发光效率和诊断准确性。在这项研究中,通过水热法制备发光的铕掺杂羟基磷灰石（EuHAp）纳米晶体，然后用（3-氨基丙基）三乙氧基硅烷（APTES）修饰，然后用FA修饰以靶向FR阳性人宫颈腺癌细胞系（HeLa）细胞。APTES和FA的顺序接枝在纳米晶体和FA之间形成稳固的共价连接。棒状FA修饰的EuHAp纳米晶体，大约100纳米的大小，在397nm激发时在589、615和650nm处显示发射峰。尽管FA改性后光致发光强度降低，荧光显微镜显示，与未修饰的EuHAp相比，强度显著增加120倍，归因于FA修饰的EuHAp的摄取增强。此外,共聚焦显微镜观察证实了FA修饰的EuHAp纳米晶体在HeLa细胞中的特异性和内在化。总之,用FA修饰EuHAp纳米晶体为增强癌症生物成像探针的诊断潜力提供了有希望的策略。
