Traceable Bioinspired Nanoparticle for the Treatment of Metastatic Breast Cancer via NIR‐Trigged Intracellular Delivery of Methylene Blue and Cisplatin,Advanced Materials

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Traceable Bioinspired Nanoparticle for the Treatment of Metastatic Breast Cancer via NIR‐Trigged Intracellular Delivery of Methylene Blue and Cisplatin
Advanced Materials ( IF 27.4 ) Pub Date : 2018-07-10 , DOI: 10.1002/adma.201802378
Yihui Zhai _{1,

2} , Wei Ran _{1,

2} , Jinghan Su _{1,

2} , Tianqun Lang _{1,

2} , Jia Meng _{1,

2} , Guanru Wang ₁ , Pengcheng Zhang _{1,

2} , Yaping Li _{1,

2,

3}

Affiliation

Cytotoxic T lymphocyte (CTL) eliminates abnormal cells through target recognition‐triggered intracellular toxin delivery. Chimeric antigen receptor T‐cell improves cancer cell recognition of CTL, but its effectiveness and safety in solid tumor treatment are still hampered by poor tumor infiltration, suppressive tumor microenvironment, and severe on‐target off‐tumor toxicity. Given the functionality and challenges of CTL in cancer therapy, herein, a CTL‐inspired nanovesicle (MPV) with a cell membrane–derived shell and a methylene blue (MB) and cisplatin (Pt) loaded gelatin nanogel core is created. The MPV generates contrast for tumor photoacoustic imaging, and produces hyperthermia upon laser irradiation, enabling photothermal imaging and deep tumor penetration. Meanwhile, it releases MB and Pt, and then delivers them into the cytosol of cancer cells, which process can be visualized by imaging the recovery of MB‐derived fluorescence. The localized hyperthermia, photodynamic therapy, and chemotherapy together kill 4T1 breast cancer cells effectively, resulting in primary tumor regression and 97% inhibition of pulmonary metastasis, without significant toxicity to the animals. Taken together, the MPV shows tumor‐specific and stimuli‐triggered intracellular toxin delivery with advantages in traceable accumulation and activation, high tumor penetration, and triple combination therapy, and thus can be an effective nanomedicine for combating metastatic breast cancer.

中文翻译：

可追踪仿生纳米颗粒通过近红外触发细胞内亚甲蓝和顺铂治疗转移性乳腺癌

细胞毒性 T 淋巴细胞 (CTL) 通过目标识别触发的细胞内毒素递送来消除异常细胞。嵌合抗原受体T细胞提高了癌细胞对CTL的识别，但其在实体瘤治疗中的有效性和安全性仍然受到肿瘤浸润不良、抑制性肿瘤微环境和严重的靶向肿瘤外毒性的阻碍。考虑到 CTL 在癌症治疗中的功能和挑战，本文创建了一种受 CTL 启发的纳米囊泡 (MPV)，其具有细胞膜衍生的外壳和亚甲基蓝 (MB) 和顺铂 (Pt) 负载的明胶纳米凝胶核心。 MPV 为肿瘤光声成像产生对比度，并在激光照射下产生热热，从而实现光热成像和深度肿瘤穿透。同时，它释放MB和Pt，然后将它们递送到癌细胞的细胞质中，这一过程可以通过对MB衍生荧光的恢复进行成像来可视化。局部热疗、光动力疗法和化疗联合有效杀灭4T1乳腺癌细胞，使原发肿瘤消退，肺转移抑制率达97%，对动物无明显毒性。综上所述，MPV表现出肿瘤特异性和刺激触发的细胞内毒素递送，具有可追踪的积累和激活、高肿瘤穿透性和三联疗法的优势，因此可以成为对抗转移性乳腺癌的有效纳米药物。

更新日期：2018-07-10

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