CAS Key Laboratory of Magnetic Materials and Devices, Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China; University of Chinese Academy of Sciences, Beijing 100049, China.
CAS Key Laboratory of Magnetic Materials and Devices, Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China.
Biomaterials. 2018 Jul;170:70-81. doi: 10.1016/j.biomaterials.2018.04.002. Epub 2018 Apr 4.
Nanoparticle-based tumor therapies are extensively studied; however, few are capable of improving patient survival time due to premature drug leakage, off target effects, and poor tissue penetration. Previously, we successfully synthesized a novel family of Y receptor (YR) ligand modified, photoluminescent BPLP nanobubbles and nanoparticles for targeted breast cancer ultrasound imaging; however, increased accumulation could also be observed in the liver, kidney, and spleen, suggesting significant interaction of the particles with macrophages in vivo. Herein, for the first time, we imparted antiphagocytosis capability to YR ligand functionalized BPLP-WPU polymeric micelles through the incorporation of a CD47 human glycoprotein based self-peptide. Application of self-peptide modified, DOX loaded micelles in vivo resulted in a 100% survival rate and complete tumor necrosis over 100 days of treatment. In vivo imaging of SPION loaded, self-peptide modified micelles revealed effective targeting to the tumor site while analysis of iron content demonstrated reduced particle accumulation in the liver and kidney, demonstrating reduced macrophage interaction, as well as a 2-fold increase of particles in the tumor. As these results demonstrate, YR ligand, self-peptide modified BPLP-WPU micelles are capable of target specific cancer treatment and imaging, making them ideal candidates to improve survival rate and tumor reduction clinically.
基于纳米粒子的肿瘤疗法得到了广泛的研究；然而，由于药物过早泄漏、脱靶效应和组织穿透性差，很少有药物能够延长患者的生存时间。之前，我们成功合成了一系列新型的 Y 受体 (YR) 配体修饰的、发荧光的 BPLP 纳米气泡和纳米颗粒，用于靶向乳腺癌超声成像；然而，在肝脏、肾脏和脾脏中也观察到了增加的聚集，这表明这些颗粒与体内的巨噬细胞有明显的相互作用。在此，我们首次通过将基于 CD47 人糖蛋白的自身肽掺入，赋予了 YR 配体功能化的 BPLP-WPU 聚合物胶束抗吞噬能力。在体内应用载有 DOX 的自肽修饰胶束后，治疗 100 天可使 100%的老鼠存活并完全肿瘤坏死。负载 SPION 的自肽修饰胶束的体内成像显示出对肿瘤部位的有效靶向，而铁含量分析表明，肝脏和肾脏中的颗粒积累减少，表明巨噬细胞相互作用减少，同时肿瘤中的颗粒增加了 2 倍。这些结果表明，YR 配体、自肽修饰的 BPLP-WPU 胶束能够进行特异性的癌症治疗和成像，使其成为提高临床生存率和肿瘤减少的理想候选物。
