Enhanced photothermal therapy of biomimetic polypyrrole nanoparticles through improving blood flow perfusion
Enhanced photothermal therapy of biomimetic polypyrrole nanoparticles through improving blood flow perfusion
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通过改善血流灌注增强仿生聚吡咯纳米粒子的光热治疗
DOI：
10.1016/j.biomaterials.2017.08.004
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发表时间：
2017
期刊：
影响因子：
14
通讯作者：
Shen Shun
中科院分区：
文献类型：
--
作者：
Wang Xuejun;Li Haichun;Liu Xianping;Tian Ye;Guo Huishu;Jiang Ting;Luo Zimiao;Jin Kai;Kuai Xinping;Liu Yao;Pang Zhiqing;Yang Wuli;Shen Shun
在这项研究中，我们报道了一种通过选择性扩张肿瘤血管来提高用于增强光热治疗的长循环仿生光热纳米制剂的输送效率的策略。通过一种简单的纳米涂层技术，在光热聚吡咯纳米颗粒(PPy@RBC NPs)表面伪装了一层天然红细胞膜。模拟红血球的PPy纳米粒继承了天然红血球的免疫逃逸能力，从而显著延长了血液保留时间。此外，由于聚吡咯纳米核的存在，还保留了优异的光热和光声成像功能。为进一步改善光热效应，联合应用内皮素A(ETA)受体拮抗剂BQ123调节肿瘤微环境。BQ123可通过调节ET-1/ETA信号转导通路，阻断ETA受体，诱导肿瘤血管松弛，增加血流灌注量，而正常组织的血管灌注量无明显变化。通过我们精心设计的策略，当系统地给药时，肿瘤部位的仿生PPy纳米粒的浓度显著提高。研究发现，仿生PPy纳米粒与特异性拮抗剂BQ123的联合抗肿瘤效果尤为显著，优于仿生PPy纳米粒(P<；)和聚乙二醇化PPy纳米粒与BQ123的联合(P<；0.01)，表明低剂量的光热制剂可以大大增强光热治疗效果。我们的发现将为其他类似的增强光热治疗提供一个有希望的程序，通过阻断ETA受体来显着增加仿生光热纳米材料的输送。
In this study, we reported a strategy to improve delivery efficiency of a long-circulation biomimetic photothermal nanoagent for enhanced photothermal therapy through selectively dilating tumor vasculature. By using a simply nanocoating technology, a biomimetic layer of natural red blood cell (RBC) membranes was camouflaged on the surface of photothermal polypyrrole nanoparticles (PPy@RBC NPs). The erythrocyte-mimicking PPy NPs inherited the immune evasion ability from natural RBC resulting in superior prolonged blood retention time. Additionally, excellent photothermal and photoacoustic imaging functionalities were all retained attributing to PPy NPs cores. To further improve the photothermal outcome, the endothelin A (ETA) receptor antagonist BQ123 was jointly employed to regulate tumor microenvironment. The BQ123 could induce tumor vascular relaxation and increase blood flow perfusion through modulating an ET-1/ETAtransduction pathway and blocking the ETAreceptor, whereas the vessel perfusion of normal tissues was not altered. Through our well-designed tactic, the concentration of biomimetic PPy NPs in tumor site was significantly improved when administered systematically. The study documented that the antitumor efficiency of biomimetic PPy NPs combined with specific antagonist BQ123 was particularly prominent and was superior to biomimetic PPy NPs (P< 0.05) and PEGylated PPy NPs with BQ123 (P< 0.01), showing that the greatly enhanced photothermal treatment could be achieved with low-dose administration of photothermal agents. Our findings would provide a promising procedure for other similar enhanced photothermal treatment by blocking ETAreceptor to dramatically increase the delivery of biomimetic photothermal nanomaterials.