设计合成纳米级锆-原卟啉框架用于肿瘤光动力/声动力协同治疗
收稿日期: 2024-01-27
网络出版日期: 2024-03-26
基金资助
国家自然科学基金(22171163); 111项目(D20015); 宜昌市自然科学研究项目(A23-2-025)
Design and Synthesis of Nanoscale Zr-Porphyrin IX Framework for Synergistic Photodynamic and Sonodynamic Therapy of Tumors
Received date: 2024-01-27
Online published: 2024-03-26
Supported by
National Natural Science Foundation of China(22171163); 111 Project(D20015); Yichang Natural Science Research Program(A23-2-025)
具有光动力和声动力性能的多功能纳米试剂在肿瘤治疗中吸引了广泛的关注, 但设计和制备“一体化”型单组分多功能纳米材料仍然具有挑战性. 因此, 本研究合成了光动力和声动力“一体化”型的锆-原卟啉IX (PpIX)配位纳米颗粒(ZrPs), 平均尺寸约为50 nm. 通过紫外吸收光谱、傅里叶红外光谱和荧光光谱研究发现ZrPs中Zr4+仅与PpIX中的羧基配位. 采用了1,3-二苯基异苯并呋喃(DPBF)作为活性氧(ROS)指示剂来测试ZrPs的光动力治疗和声动力治疗的效果. 在光照/超声激发条件下(5 min), 发现分别有59.7%(光)和22.8%(超声)的DPBF被ZrPs产生的ROS氧化, 表明ZrPs可作为多功能纳米材料在光/超声条件下高效地产生ROS. 此外, ZrPs 在体外细胞实验中显示出良好的生物安全性, 可以被肿瘤细胞有效内吞/摄取. 同时细胞内的ZrPs在光/超声激发条件下可以高效地产生ROS用于光动力/声动力治疗杀死肿瘤细胞. 因此, 本研究不仅提出了ZrPs可以作为PDT-SDT 治疗的“all-in-one”型多功能纳米材料, 而且为设计其它具有与PpIX结构相似的光/声敏剂分子用于生物应用领域提供了一些见解.
李燕 , 王玮 , 张毓婷 , 肖述章 , 兰海闯 , 耿鹏 . 设计合成纳米级锆-原卟啉框架用于肿瘤光动力/声动力协同治疗[J]. 化学学报, 2024 , 82(4) : 443 -448 . DOI: 10.6023/A24010035
Multifunctional nanomaterials with photodynamic and sonodynamic properties have attracted wide attention in tumor therapy, but the design and preparation of “all-in-one” type of multifunctional nanomaterials with single component remains challenging. Herein the “all-in-one” type of Zr-PpIX (protoporphyrin IX) coordination nanoparticles (ZrPs) with photodynamic and sonodynamic properties was reported as efficient nano-photo/sonosensitizers. The ZrPs had an average size of about 50 nm. The survey X-ray photoelectron spectroscopy (XPS) spectrum showed strong Zr, C, N and O elemental signals, verifying that the ZrPs were composed of Zr/C/N/O elements. In addition, Fourier transform infrared (FTIR) spectra, ultraviolet-visible (UV-Vis) spectra and fluorescence (FL) spectra showed that the Zr4+ ion was only coordinated with the carboxyl group of PpIX. The ZrPs contained photo/sono-sensitizers PpIX, which could be excited by light/ultrasonic (US) to transform O2 into cytotoxic 1O2. Furthermore, the 1O2 can be detected by using 1,3-diphenylisobenzofuran (DPBF) assay. When the mixed solution (ZrPs+DPBF) was excited by light, the peak of DPBF decreased rapidly as the light irradiation time increased, which suggested the generation of 1O2 by ZrPs+light. Similarly, the absorbance of DPBF+ZrPs was reduced as the US time increased, which confirmed the sonodynamic effect of ZrPs+US. After 5 min of light/US irradiation, 59.7% (light) and 22.8% (US) of DPBF was found to be oxidized by ZrPs, which showed effective ROS generation for photodynamic/sonodynamic therapy. Besides, ZrPs had shown good biosafety in vitro cellular experiments. ZrPs can be effectively endocytosed/uptaken by tumor cells. Meanwhile, ZrPs within cells can generate ROS upon light/US, affording photodynamic and/or sonodynamic effects. After 5 min of ZrPs with light/US irradiation, the cell viability goes down rapidly from about 100% to 5.3%. Therefore, the present study not only represents ZrPs as an “all-in-one” type of multifunctional nanomaterials for PDT-SDT therapy, but also provides some insights for designing other PpIX-related molecules with the similar structure for bioapplication.
Key words： all-in-one; protoporphyrin IX; photodynamic therapy; sonodynamic therapy
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