Unique Photochemo-Immuno-Nanoplatform against Orthotopic Xenograft Oral Cancer and Metastatic Syngeneic Breast Cancer.
Unique Photochemo-Immuno-Nanoplatform against Orthotopic Xenograft Oral Cancer and Metastatic Syngeneic Breast Cancer.
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针对原位异种移植口腔癌和转移性合成性乳腺癌的独特光化学 - 免疫纳米植物。
DOI：
10.1021/acs.nanolett.8b03096
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发表时间：
2018-11-14
期刊：
影响因子：
10.8
通讯作者：
Lam KS
中科院分区：
文献类型：
--
作者：
Zhang L;Jing D;Wang L;Sun Y;Li JJ;Hill B;Yang F;Li Y;Lam KS
复杂的自组装可以赋予材料各种独特的功能，这些功能对于治疗性纳米平台是非常理想的。在这里，我们报告的两个结构定义的telodendrimers，每个由亲水性线性PEG和疏水性胆酸簇作为一个基本的两亲性分子亚基的共组装。一个telodendrimer具有四个添加的吲哚菁绿色衍生物，导致优异的光热性能;另一个telodendrimer具有四个巯基，设计用于有效的亚基间交联，有助于在循环过程中的上级稳定性。共组装纳米粒子（CPCI-NP）具有上级光热转换效率以及对细胞毒性分子和免疫调节剂的有效包封和控制释放。负载有阿霉素的CPCI-NP已被证明是针对原位OSC-3口腔癌异种移植模型的高效组合光热/化学治疗纳米平台。当负载有咪喹莫特（一种有效的小分子免疫刺激剂）时，发现CPCI-NP对4 T1同基因鼠乳腺癌模型高度有效，特别是当光热/免疫疗法与PD-1检查点阻断抗体组合给予时。这种三联疗法不仅根除了光照射的原发性肿瘤，而且还激活了全身抗肿瘤免疫活性，导致未暴露于光的远处肿瘤部位的肿瘤死亡。这种共组装的多功能、通用且易于扩展的光热免疫纳米平台显示出巨大的临床转化前景。
Sophisticated self-assembly may endow materials with a variety of unique functions that are highly desirable for therapeutic nanoplatform. Herein, we report the co-assembly of two structurally-defined telodendrimers, each comprised of hydrophilic linear PEG and hydrophobic cholic acid cluster as a basic amphiphilic molecular subunit. One telodendrimer has four added indocyanine green derivatives, leading to excellent photothermal properties; the other telodendrimer has four sulfhydryl groups designed for efficient inter-subunit cross-linking, contributing to superior stability during circulation. The co-assembled nanoparticle (CPCI-NP) possesses superior photothermal conversion efficiency as well as efficient encapsulation and controlled release of cytotoxic molecules and immunomodulatory agents. CPCI-NP loaded with doxorubicin has proven to be a highly efficacious combination photothermal/chemo-therapeutic nanoplatform against orthotopic OSC-3 oral cancer xenograft model. When loaded with imiquimod, a potent small molecule immunostimulant, CPCI-NP was found to be highly effective against 4T1 syngeneic murine breast cancer model, particularly when photothermal/immuno-therapy is given in combination with PD-1 checkpoint blockade antibody. Such triple therapy not only eradicates the light-irradiated primary tumors, but also activates systemic anti-tumor immunoactivity, causing tumor death at light-unexposed distant tumor sites. This co-assembled multi-functional, versatile, and easily scalable photothermal immuno-nanoplatform shows great promise for clinical translation.
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