Combined Prussian Blue Nanozyme Carriers Improve Photodynamic Therapy and Effective Interruption of Tumor Metastasis.
Combined Prussian Blue Nanozyme Carriers Improve Photodynamic Therapy and Effective Interruption of Tumor Metastasis.
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DOI：
10.2147/ijn.s359156
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发表时间：
2022
影响因子：
8
通讯作者：
Pei P
中科院分区：
文献类型：
--
作者：
Shen W;Han G;Yu L;Yang S;Li X;Zhang W;Pei P
光动力学疗法（photodynamic therapy，PDT）是一种新型的治疗诊断技术，它通过激活光敏剂并与氧气（oxygen，O2）相互作用产生活性氧（reactive oxygen species，ROS）来杀伤肿瘤细胞。然而，缺氧的肿瘤微环境（TME）可能会限制PDT的疗效。此外，TME中O2的缺乏还上调了HIF-1α的表达并促进肿瘤转移，这也是晚期癌症患者死亡的主要原因。采用水热法合成普鲁士蓝（PBs），然后用盐酸刻蚀得到空心普鲁士蓝纳米粒子（HPBs）。然后，采用还原法在HPBs上原位生长Au-Pt纳米酶，制备Au-Pt@HPBs（APHPBs）。由于APHPBs的中空结构，光敏剂Ce 6可以容易、高效地负载到APHPBs中，从而得到Ce 6-Au-Pt@HPBs（Ce 6-APHPBs）。在ce 6-APHPBS调节后，然后使用光声成像和缺氧荧光成像来评估体内缺氧TME的变化。最后，在Ce 6-APHPBs的辅助下，我们评价了增强的PDT对原发性和转移性肿瘤的抑制作用。我们首次设计并合成了Ce 6-APHPBs，并在其上原位生长了Au-Pt纳米酶，体内外实验表明，制备的Ce 6-APHPBs具有良好的生物安全性，能有效降解TME中过表达的H2 O2产生O2，进一步缓解TME缺氧，增强PDT的疗效。同时，增加O2含量也可降低肿瘤部位HIF-1α的表达，从而减少肺转移。我们设计的Ce 6-APHPBs不仅能有效地增强PDT治疗，而且能调节TME，减少肿瘤转移，延长小鼠生存期，为临床PDT治疗转移性肿瘤提供了新的思路和策略。
Photodynamic therapy (PDT) as a new technique for theranostics is to kill tumor cells by activating photosensitizer and interacting with oxygen (O2) to produce reactive oxygen species (ROS). However, the hypoxic tumor microenvironment (TME) may constrain the efficacy of PDT. Moreover, the lack of O2 in TME also up-regulates the expression of HIF-1α and promotes tumor metastasis, which is also a leading cause of death for terminal cancer patients. Prussian blue (PBs) was firstly synthesized by hydrothermal method, which was then etched by hydrochloric acid to obtained hollow Prussian blue nanoparticles (HPBs). Afterwards, Au-Pt nanozymes were in situ growing on the HPBs by reduction method to prepare Au-Pt@HPBs (APHPBs). Owing to the hollow structure of APHPBs, photosensitizer Ce6 can be easily and efficiently loaded into it to obtain Ce6-Au-Pt@HPBs (Ce6-APHPBs). After ce6-APHPBS regulation, photoacoustic imaging and hypoxic fluorescence imaging were then used to evaluate changes in hypoxic TME in vivo. Finally, under the assistant of Ce6-APHPBs, we evaluated the inhibitory effect of enhanced PDT on primary and metastatic tumors. We first designed and synthesized Ce6 loaded hollow prussian blue nanoparticles with Au-Pt nanozymes grown in situ on it. Both in vitro and in vivo experiments show that the prepared Ce6-APHPBs have good biosafety and could effectively degrade the overexpressed H2O2 in TME to generate O2, further relieve the hypoxic TME and thus enhance the effect of PDT. At the same time, the increasing O2 content could also reduce the expression of HIF-1α at the tumor site, which could reduce lung metastasis. Ce6-APHPBs designed by us could not only efficiently enhance PDT but also regulate TME to reduce tumor metastasis and prolong survival of mice, which provide a novel idea and strategy for clinical PDT and metastatic tumor.