Department of Radiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, People's Republic of China.
Int J Nanomedicine. 2022 Nov 22;17:5605-5619. doi: 10.2147/IJN.S374293. eCollection 2022.
Owing to the lack of effective biomarkers, triple-negative breast cancer (TNBC) has the worst prognosis among all subtypes of breast cancer. Meanwhile, tremendous progress has been made to identify biomarkers for TNBC. However, limited number of biomarkers still restrain the specifically targeting outcomes against TNBC. Here, to solve the obstacle, we designed and synthesized a new type of biocompatible nanoparticles to amplify the targeting effects for TNBC theranostics.
To identify the biomarker of TNBC, the expression of intercellular adhesion molecule-1 (ICAM1) was assessed by real-time polymerase chain reaction and western blot among all subtypes of breast cancer and normal breast epithelium. Then, vesicular nanoparticles based on poly(ethylene glycol)-poly(ε-caprolactone) copolymers were prepared by the double emulsion method and modified with anti-ICAM1 antibodies through click chemistry to conjugate with related antigens on TNBC cell membranes and then loaded with magnetic resonance imaging (MRI) contrast agent gadolinium and chemotherapeutic drug doxorubicin. The targeting capability, diagnostic and therapeutic efficacy of this nanoparticle were validated through cell-based and tumor model-based experiments.
ICAM1 was expressed significantly higher on TNBC than on other subtypes of breast cancer and normal breast epithelium in both mRNA and protein level. Theranostic nanoparticle modified with anti-ICAM1 was proved to be able to specifically target to TNBC in vitro experiments. Such theranostic nanoparticle also displayed enhanced diagnostic and therapeutic efficacy by specifically targeting capability and extending circulation time in tumor models. The biocompatibility and biosafety of this nanoparticle was also confirmed in vitro and in vivo.
Overall, this new nanoparticle has been demonstrated with effective therapeutic outcomes against TNBC, providing a promising theranostic approach for MRI-guided therapy of TNBC.
由于缺乏有效的生物标志物，三阴性乳腺癌（TNBC）在所有乳腺癌亚型中预后最差。同时，已经取得了巨大的进展来鉴定 TNBC 的生物标志物。然而，有限数量的生物标志物仍然限制了针对 TNBC 的靶向治疗效果。在这里，为了解决这一障碍，我们设计并合成了一种新型的生物相容性纳米颗粒，以增强 TNBC 治疗学的靶向效果。
为了鉴定 TNBC 的生物标志物，通过实时聚合酶链反应和蛋白质印迹法在所有乳腺癌亚型和正常乳腺上皮中评估细胞间黏附分子 1（ICAM1）的表达。然后，通过双重乳液法制备基于聚（乙二醇）-聚（ε-己内酯）共聚物的囊泡纳米颗粒，并通过点击化学将其与抗 ICAM1 抗体修饰，与 TNBC 细胞膜上的相关抗原结合，然后装载磁共振成像（MRI）造影剂钆和化疗药物阿霉素。通过基于细胞的和基于肿瘤模型的实验验证了该纳米颗粒的靶向能力、诊断和治疗效果。
ICAM1 在 TNBC 中的 mRNA 和蛋白水平均明显高于其他乳腺癌亚型和正常乳腺上皮。用抗 ICAM1 修饰的治疗性纳米颗粒被证明能够在体外实验中特异性地靶向 TNBC。这种治疗性纳米颗粒还通过特异性靶向和延长在肿瘤模型中的循环时间显示出增强的诊断和治疗效果。该纳米颗粒的生物相容性和生物安全性也在体外和体内得到了证实。
总的来说，这种新的纳米颗粒已被证明对 TNBC 具有有效的治疗效果，为 MRI 引导的 TNBC 治疗提供了一种有前途的治疗方法。
