Li Jing, He Hongyi, Liu Shuyan, Li Xining, Wu Fengfeng
Neurobiology Laboratory, Wannan Medical College, Wuhu, China.
College of Pharmacy, Hubei University of Science and Technology, Xianning, China.
Front Oncol. 2024 Jun 12;14:1404148. doi: 10.3389/fonc.2024.1404148. eCollection 2024.
Tumor-specific fluorescent probes must fulfill the dual requirements of targeted accumulation within tumors and high-resolution imaging capabilities. To achieve both tumor-targeted accumulation and high-resolution imaging performance, we developed a composite comprising an acid-responsive bodipy conjugated to amphiphilic PEG-b-PLA polymer, along with folic acid (FA)-modified PEG-b-PLA as a targeting moiety for active tumor-specific accumulation. Finally, a novel assembly of hybrid fluorescent nanoparticles was successfully synthesized by integrating these two components, demonstrating exceptional responsiveness to acidic conditions for fluorescence excitation and remarkable tumor-targeted accumulation capabilities. We conducted comprehensive and investigations employing techniques such as analysis of physicochemical properties, fluorescence-based probes detection at varying pH levels, assessment of cytotoxicity, evaluation of cellular uptake capacity, analysis of lysosomal co-localization imaging, examination of tumor fluorescence images , and investigation of biological distribution patterns. The results demonstrated that the acid-responsive nanofluorescence probe we designed and synthesized possesses desirable physical and chemical characteristics, including a small particle size and low cytotoxicity. Moreover, it exhibits rapid real-time response to acidic environments and displays enhanced fluorescence intensity, enabling the real-time tracking of probe entry into tumor cells as well as intracellular lysozyme accumulation. We achieved highly specific tumor visualization by combining nanoprobes targeting folate receptor. Through imaging cervical tumor mice, we demonstrated the precise imaging performance and high targeted accumulation of FA-targeted nanofluorescence probes in tumor tissue. Furthermore, we confirmed the safety of the FA-targeted nanofluorescence probe through biological distribution analysis. These findings highlight the potential widespread application of FA-targeted acid-responsive nanofluorescence probes for selective imaging of tumor cells and tissues.
肿瘤特异性荧光探针必须满足在肿瘤内靶向聚集和具备高分辨率成像能力这两个要求。为了同时实现肿瘤靶向聚集和高分辨率成像性能，我们开发了一种复合材料，它由与两亲性聚乙二醇-聚乳酸（PEG-b-PLA）聚合物共轭的酸响应性硼二吡咯（bodipy）组成，同时还有叶酸（FA）修饰的PEG-b-PLA作为活性肿瘤特异性聚集的靶向部分。最后，通过整合这两种成分成功合成了一种新型的混合荧光纳米颗粒组装体，它对酸性条件下的荧光激发表现出优异的响应性以及显著的肿瘤靶向聚集能力。我们采用了多种技术进行全面研究，如物理化学性质分析、不同pH水平下基于荧光的探针检测、细胞毒性评估、细胞摄取能力评估、溶酶体共定位成像分析、肿瘤荧光图像检查以及生物分布模式研究。结果表明，我们设计合成的酸响应性纳米荧光探针具有理想的物理和化学特性，包括小粒径和低细胞毒性。此外，它对酸性环境表现出快速实时响应，并显示出增强的荧光强度，能够实时追踪探针进入肿瘤细胞以及细胞内溶酶体的积累情况。通过结合靶向叶酸受体的纳米探针，我们实现了高度特异性的肿瘤可视化。通过对宫颈癌小鼠成像，我们证明了FA靶向纳米荧光探针在肿瘤组织中的精确成像性能和高靶向聚集能力。此外，我们通过生物分布分析证实了FA靶向纳米荧光探针的安全性。这些发现突出了FA靶向酸响应性纳米荧光探针在肿瘤细胞和组织选择性成像方面广泛应用的潜力。
