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Peptide-enhanced tumor accumulation of upconversion nanoparticles for sensitive upconversion luminescence/magnetic resonance dual-mode bioimaging of colorectal tumors.
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.actbio.2020.01.003
Xinxin Li 1 , Lin Liu 2 , Yu Fu 1 , Hongda Chen 3 , Murad M A Abualrejal 3 , Hua Zhang 3 , Zhenxin Wang 3 , Huimao Zhang 1
Affiliation  

Currently, it is still a great challenge to develop tumor targeting nanoparticles with high sensitivity and high resolution for improving the non-invasive detection ability of colorectal cancer (CRC) at an early stage. In this study, NaErF4:Yb@NaGdF4:Yb core@shell upconversion nanoparticles (UCNPs) were prepared with high upconversion luminescence (UCL) emission in red light region through adjusting the doping ratios of Er and Yb elements in the core. For biomedical applications, the carboxyl-terminated silica shell was introduced to transfer the as-prepared UCNPs from the organic phase to the aqueous phase, and allowed conjugation with peptide ligands derived from the l-SP5 peptide (i.e., l-SP5-H and l-SP5-C), respectively. Due to the tumor-targeting affinity of the PSP motif in the peptide ligands, the as-prepared peptide functionalized UCNPs (UCNP@SiO2-l-SP5-H and UCNP@SiO2-l-SP5-C) can be used as an active tumor targeting contrast agents for UCL/T1-weighted magnetic resonance (MR) dual-mode imaging. Both the in vitro and in vivo experimental results demonstrated that UCNP@SiO2-l-SP5-C has relatively high affinity for the HCT116 CRC subtype. Moreover, UCNP@SiO2-l-SP5-C can visualize ultra-small subcutaneous xenografted HCT116 tumors (c.a. 13 mm3 in volume) by in vivo UCL imaging. STATEMENT OF SIGNIFICANCE: 1. High red emission UCNPs were synthesized for tumor-targeting dual-mode bioimaging. 2. With tumor-binding affinity peptide, UCNP@SiO2-l-SP5-C shows high HCT116 tumor targeting ability. 3. UCNP@SiO2-l-SP5-C successfully achieves sensitive detection of ultrasmall HCT116 tumors.

中文翻译:

上转换纳米颗粒的肽增强肿瘤积累,可用于结直肠肿瘤的敏感上转换发光/磁共振双模生物成像。

当前,开发具有高灵敏度和高分辨率的靶向肿瘤的纳米颗粒以在早期改善大肠癌(CRC)的非侵入性检测能力仍然是巨大的挑战。在本研究中,通过调节核中Er和Yb元素的掺杂比例,制备了在红光区具有高上转换发光(UCL)发射的NaErF4:Yb @ NaGdF4:Yb核@壳上转换纳米粒子(UCNPs)。对于生物医学应用,引入了羧基封端的硅胶壳,将制得的UCNP从有机相转移至水相,并与衍生自1-SP5肽的肽配体(即1-SP5-H和1-SP5-C)。由于肽配体中PSP基序的肿瘤靶向亲和力,制备的肽功能化UCNP(UCNP @ SiO2-1-SP5-H和UCNP @ SiO2-1-SP5-C)可用作UCL / T1加权磁共振(MR)双重靶向的活性肿瘤靶向造影剂模式成像。体外和体内实验结果均证明UCNP @ SiO2-1-SP5-C对HCT116 CRC亚型具有相对高的亲和力。此外,UCNP @ SiO2-1-SP5-C可以通过体内UCL成像可视化超小皮下异种移植HCT116肿瘤(体积约13 mm3)。意义声明:1.合成了高红色发射的UCNP,用于靶向肿瘤的双模式生物成像。2.具有肿瘤结合亲和力肽的UCNP @ SiO2-1-SP5-C显示出高的HCT116肿瘤靶向能力。3. UCNP @ SiO2-1-SP5-C成功实现了超小型HCT116肿瘤的灵敏检测。
更新日期:2020-01-07
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