Fluorescent nanoprobe prepared from hyaluronic acid modified iron selenide nanoparticles for real-time detection of hyaluronidase as tumor marker

Chaoqun Zhang , Jie Song , Xin Shen , Qian Li , Feng Su , Suming Li
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Abstract

A highly sensitive nanoprobe HAPPF@FeSe2NPs was developed for real-time detection of hyaluronidase (HAase) as tumor marker. Hyaluronic acid (HA) was first functionalized with adipic acid dihydrazide (ADH) via amide formation. Carboxyl-terminated polylactide (PLA) was then grafted to HA-ADH using EDC/NHS as coupling agents, yielding an HA-ADH-PLA (HAP) graft copolymer. Iron selenide nanoparticles (FeSe2NPs) were surface coated with HAP by ultrasonic assisted self-assembly. Finally, the resulted HAP@FeSe2NPs were surface-modified with fluorescein isothiocyanate (FITC) and polyethyleneimine (PEI) to obtain HAPPF@FeSe2NPs fluorescent nanoprobe. Analyses by FTIR, XRD, XPS, EDX, TEM, DLS, 1H NMR and TGA confirmed the successful synthesis of the nanoprobe, and fluorescence spectroscopy proved its good detection performance. Moreover, cell imaging results demonstrated the ability of the nanoprobe to target tumor cells. MTT assay and hemolysis tests confirmed its good cyto- and hemo-compatibility. Therefore, it is concluded that HAPPF@FeSe2NPs nanoprobe could be used in targeted tumor cell imaging for early diagnosis of cancers.

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透明质酸修饰的硒化铁纳米颗粒制备荧光纳米探针用于实时检测透明质酸酶作为肿瘤标志物
开发了一种高灵敏度纳米探针HAPPF@FeSe2NPs,用于实时检测透明质酸酶(HAase)作为肿瘤标志物。透明质酸(HA)首先通过酰胺形成与己二酸二肼(ADH)功能化。然后以EDC/NHS为偶联剂将端羧基聚乳酸(PLA)接枝到HA-ADH上,得到HA-ADH-PLA (HAP)接枝共聚物。采用超声辅助自组装的方法在硒化铁纳米颗粒(FeSe2NPs)表面包覆HAP。最后,用异硫氰酸荧光素(FITC)和聚乙烯亚胺(PEI)对所得HAP@FeSe2NPs进行表面修饰,得到HAPPF@FeSe2NPs荧光纳米探针。通过FTIR、XRD、XPS、EDX、TEM、DLS、1H NMR和TGA分析证实了纳米探针的成功合成,荧光光谱分析证实了其良好的检测性能。此外,细胞成像结果证明了纳米探针靶向肿瘤细胞的能力。MTT试验和溶血试验证实其具有良好的细胞和血液相容性。因此,HAPPF@FeSe2NPs纳米探针可用于肿瘤细胞靶向成像,早期诊断癌症。
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