CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Ingenious designed a HER2-Specific macrophage biomimetic multifunctional nanoplatform for enhanced bio-photothermal synergistic therapy in HER2 positive breast cancer.
Ingenious designed a HER2-Specific macrophage biomimetic multifunctional nanoplatform for enhanced bio-photothermal synergistic therapy in HER2 positive breast cancer.
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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。
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.
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