文献：A metal protoporphyrin-induced nano-self-assembly for potentiating photothermal therapy by depleting antioxidant defense systems

文献链接：https://www.sciencedirect.com/science/article/abs/pii/S1385894721013541

作者：Huizhu Yu , Ming Ma ,, Liping Jiang , Jie Shen , Fengfeng Xue , Hangrong Chen

相关产品：DSPE-PEG2000-NH2（磷脂-聚乙二醇2000-氨基）

原文摘要：

Nanomaterial-mediated low-temperature photothermal therapy (PTT) by integrating photothermal agent and heat shock proteins (HSPs) inhibitor holds great potential application in antitumor treatment. A nanoplatform performing improved therapeutic effect that constructed at large scale with green synthesis, high drug loading efficiency, high drug loading capacity, and low cost is highly desired. Herein, we report a metal protoporphyrininduced self-assembling nanoagent (ZCNA) by integration of hydrophobic Cu2-xS nanoparticles and zinc protoporphyrin (ZnPP) via a facile volatilization-driven approach without using of any additional stabilizing or carrier material. This nanoagent is featured with simplified preparation, high ZnPP loading efficiency, high ZnPP loading capacity, and excellent biocompatibility. ZCNA acts as a contrast agent for photoacoustic imaging and a photothermal agent for PTT. Meanwhile, the released ZnPP from ZCNA could resist the expression of an important type of HSPs, heme oxygenase-1 (HO-1), and thereby deplete the antioxidant defense systems of tumor cells during PTT, which is responsible for the significantly enhanced antitumor effect of ZCNA in lowtemperature PTT in comparison with the non-ZnPP containing Cu2-xS-based nanoagent both in vitro and in vivo. Overall, the ingeniously constructed ZCNA can be an effective theranostic platform with photoacoustic imaging capability and synergistic antitumor effect to advance the clinical translation of low-temperature PTTbased tumor therapy.

DSPE（1,2 - 二硬脂酰 - sn - 甘油 - 3 - 磷酸乙醇胺）是一种磷脂成分，具有亲脂性的长链脂肪酸（硬脂酸）部分，可以插入脂质双层中，这使得它在脂质体等脂质结构的构建中有重要作用。PEG2000 代表聚乙二醇的分子量约为 2000，聚乙二醇链具有良好的亲水性，可以增加化合物的水溶性，并且能够减少与生物体内免疫系统的非特异性相互作用，延长化合物在体内的循环时间。NH₂（氨基）是一个活性官能团，可以用于与其他带有活性基团（如羧基、醛基等）的分子进行化学反应，例如通过酰胺键或席夫碱反应等进行偶联，用于化合物递送系统中化合物的连接或生物分子的标记等。基于DSPE-PEG2000-NH2的性能，制备自组装纳米剂ZCNA流程如下：

图：合成示意图

ZnPP/Cu2-xS纳米剂的制备：

将ZnPP溶解在DMSO中，然后加入分散在甲苯中的Cu2-xS纳米颗粒。然后涡旋，直到ZnPP和Cu2-xS完全溶解。随后，将上述混合物快速注入到含有水的玻璃小瓶中，然后超声处理，得到均匀的水中油微乳液。接下来，将玻璃小瓶放置在黑暗中过夜，以通过蒸发去除甲苯。将自组装的ZnPP/Cu2-xS纳米剂透析，离心，分别去除DMSO和其余的游离ZnPP。最后，将ZnPP/Cu2-xS纳米剂分散在水中，以进行进一步的表征和应用。

聚乙二醇化Cu2-xS的制备：

PpIX/Cu2-xS纳米剂是通过相同的自组装策略合成的。将PpIX与50µL的DMSO混合，加入含有Cu2-xS纳米颗粒的甲苯中，然后进行超声处理、去除甲苯、透析和离心。首先，将DSPE-PEG2000-NH2溶解到含有Cu2-xS纳米颗粒的氯仿溶液中，然后超声处理。然后，利用旋转蒸发器去除有机溶剂。随后，将去离子水加入脂层瓶中，超声形成聚乙二醇化Cu2-xS。

图：作用机制

结论：

该文献成功制备出了一种基于DSPE-PEG2000-NH2的金属原卟啉诱导的自组装纳米剂（ZCNA）。实验数据表明，相比于其他类型的纳米剂，该纳米剂具有制备简单、ZnPP加载效率高、ZnPP加载能力高、生物相容性好等特点。