研究动态
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使用负载阿霉素的抗PD-L1抗体缀合金纳米壳聚(乳酸-乙醇酸)纳米胶囊:一种用于三阴性乳腺癌超声成像和光热/化疗联合治疗的治疗诊断剂。

Using anti-PD-L1 antibody conjugated gold nanoshelled poly (Lactic-co-glycolic acid) nanocapsules loaded with doxorubicin: A theranostic agent for ultrasound imaging and photothermal/chemo combination therapy of triple negative breast cancer.

发表日期:2023 Nov 09
作者: Hui Jiang, Yingying Zhou, Dongdong Zheng, Yexiazi Cheng, Dacheng Xiang, Lixin Jiang, Jing Du
来源: Cell Death & Disease

摘要:

三阴性乳腺癌(TNBC)是所有乳腺癌中预后最差的,通过传统化疗很难取得进展。因此,TNBC的治疗迫切需要具有有效诊断和治疗能力的药物。在这项研究中,我们获得了程序性死亡配体1(PD-L1)抗体缀合金纳米壳聚(乳酸-乙醇酸)(PLGA)纳米胶囊(NC)封装阿霉素(DOX)(DOX@PLGA@Au-PD- L1 NC)。采用改进的单乳液水包油(O/W)溶剂蒸发法制备包封DOX的PLGA NCs,并通过金种子生长法在表面形成金纳米壳,并通过碳二亚胺与PD-L1抗体偶联方法。所制造的 DOX@PLGA@Au-PD-L1 NC 在体外超声成像中表现出有希望的对比度增强效果。此外,封装在 NC 中的 DOX 显示出良好的 pH 响应和光触发药物释放特性。用激光照射200μg/mL NCs溶液10min后,溶液温度升高近23℃,表明NCs具有良好的光热转换能力。靶向实验证实NCs对过表达PD-L1分子的TNBC细胞具有特异性靶结合能力。细胞实验表明,该药剂通过光化疗联合治疗显着降低了TNBC细胞的存活率。作为一种多功能诊断剂,DOX@PLGA@Au-PD-L1 NCs 可用于 TNBC 细胞的超声靶向对比成像和光化疗联合治疗,为 TNBC 的早期诊断和治疗提供了一个有前景的思路。© 2023 Wiley periodicals LLC。
Triple negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and it is difficult to progress through traditional chemotherapy. Therefore, the treatment of TNBC urgently requires agents with effective diagnostic and therapeutic capabilities. In this study, we obtained programmed death-ligand 1 (PD-L1) antibody conjugated gold nanoshelled poly(lactic-co-glycolic acid) (PLGA) nanocapsules (NCs) encapsulating doxorubicin (DOX) (DOX@PLGA@Au-PD-L1 NCs). PLGA NCs encapsulating DOX were prepared by a modified single-emulsion oil-in-water (O/W) solvent evaporation method, and gold nanoshells were formed on the surface by gold seed growth method, which were coupled with PD-L1 antibodies by carbodiimide method. The fabricated DOX@PLGA@Au-PD-L1 NCs exhibited promising contrast enhancement in vitro ultrasound imaging. Furthermore, DOX encapsulated in NCs displayed good pH-responsive and photo-triggered drug release properties. After irradiating 200 μg/mL NCs solution with a laser for 10 min, the solution temperature increased by nearly 23°C, indicating that the NCs had good photothermal conversion ability. The targeting experiments confirmed that the NCs had specific target binding ability to TNBC cells overexpressing PD-L1 molecules. Cell experiments exhibited that the agent significantly reduced the survival rate of TNBC cells through photochemotherapy combination therapy. As a multifunctional diagnostic agent, DOX@PLGA@Au-PD-L1 NCs could be used for ultrasound targeted contrast imaging and photochemotherapy combination therapy of TNBC cells, providing a promising idea for early diagnosis and treatment of TNBC.© 2023 Wiley Periodicals LLC.