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巧妙设计了一种 HER2 特异性巨噬细胞仿生多功能纳米平台,用于增强 HER2 阳性乳腺癌的生物-光热协同治疗

英文原题:Ingenious designed a HER2-Specific macrophage biomimetic multifunctional nanoplatform for enhanced bio-photothermal synergistic therapy in HER2 positive breast cancer.

查看英文原题

Ingenious designed a HER2-Specific macrophage biomimetic multifunctional nanoplatform for enhanced bio-photothermal synergistic therapy in HER2 positive breast cancer.

PubMed 2024/05/20(内容时间) Mater Today Bio Q1 · IF 11(JCR 2025)

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中文摘要

光热治疗(PTT)作为一种高效的癌症治疗策略已受到广泛关注。遗憾的是,由于在解决血液循环和肿瘤蓄积方面存在挑战,目前尚无能够有效治疗HER2阳性乳腺癌(HER2 + BC)的合适光热剂(PTAs)。

在此,我们提出了一种HER2特异性巨噬细胞仿生纳米平台IR820@ZIF-8@EM(AMBP),用于增强HER2 + BC的生物光热治疗。利用跨膜表达技术在工程化巨噬细胞中表达了抗HER2抗体。作为高效PTAs,IR820染料被组装到ZIF-8中,以开发一种“纳米热炸弹”。同源建模方法支持所表达的抗HER2抗体能够特异性识别HER2受体。

此外,AMBP还能在HER2 + BC细胞中诱导抗体依赖性细胞介导的细胞毒性。体外荧光共聚焦成像显示,AMBP促进了HER2 + 癌细胞的摄取,而体内抗肿瘤实验表明,AMBP能高效蓄积在肿瘤区域。

最后,在时空控制的近红外(NIR)照射下,AMBP治疗小鼠的六个肿瘤中有三个被根除,证明了一种安全有效的策略。总之,我们的研究为抗体特异性巨噬细胞开辟了新范式,预计这些特性在BC治疗中具有巨大的临床转化潜力。

展开英文摘要原文

Photothermal therapy (PTT) has garnered extensive attention as an efficient strategy for cancer therapy. Unfortunately, there are currently no suitable photothermal agents (PTAs) capable of effectively treating HER2-positive breast cancer (HER2 + BC) due to the challenges in addressing blood circulation and tumor accumulation.

Here, we propose a HER2-specific macrophage biomimetic nanoplatform IR820@ZIF-8@EM (AMBP) for enhanced bio-photothermal therapy of HER2 + BC. An anti-HER2 antibody was expressed in engineered macrophages using the transmembrane expression technique. As an efficient PTAs, IR820 dyes were assembled into ZIF-8 as to develop a "nano-thermal-bomb". Homology modeling methods support that the expressed anti-HER2 antibody can specifically recognize the HER2 receptor.

Moreover, antibody-dependent cell-mediated cytotoxicity can also be induced in HER2 + BC cells by AMBP. In vitro fluorescence confocal imaging showed that AMBP promoted the uptake of HER2 + cancer cells while in vivo anti-tumor experiments demonstrated that AMBP efficiently accumulates in the tumor regions.

Finally, under spatiotemporally controlled near-infrared (NIR) irradiation, three of the six tumors were eradicated in AMBP-treated mice, demonstrating a safe and effective strategy.

In conclusion, our research opens a new paradigm for antibody-specific macrophage, and it is expected that these characteristics will have substantial clinical translation potential for BC treatment.

论文信息

作者
Yang P、Du F、Zhang W、Liu W、Ye Z、Fan H、Yu J、von Deneen KM
单位
School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710071, PR China.China
期刊
Materials today. Bio2024 Jun
原文标识
PubMed 38840796 · DOI 10.1016/j.mtbio.2024.101095