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载血红蛋白血小板减轻肿瘤乏氧并增强低剂量 X 射线放射治疗效果

Au-Hemoglobin Loaded Platelet Alleviating Tumor Hypoxia and Enhancing the Radiotherapy Effect with Low-Dose X-ray.

机构信息

Institute of Materials Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing, Jiangsu 210093, P. R. China.

School of Public Health, Nantong University, Nantong, Jiangsu 226019, P. R. China.

出版信息

ACS Nano. 2020 Nov 24;14(11):15654-15668. doi: 10.1021/acsnano.0c06541. Epub 2020 Oct 27.

Abstract

Radiotherapy (RT) is a widely explored clinical modality to combat cancer. However, its therapeutic efficacy is not always satisfied because of the severe hypoxic microenvironment in solid tumors and the high dosage of radiation harmful to the adjacent healthy tissue. Herein, Au nanoparticle-hemoglobin complex nanoparticle loaded platelets (Au-Hb@PLT) were fabricated. These Au-Hb@PLT would be activated by tumor cells, and the formed platelet-derivate particles (PM) could deliver Au nanoparticle-hemoglobin complex deeply into tumor tissue because of their small size and tumor homing ability. Hemoglobin acts as an oxygen carrier to relieve the hypoxia and gold nanoparticles work as radiosensitizers to potentiate the sensitivity of tumor cells to X-ray, thus, enhancing the therapeutic outcome even under a low-dose RT in tumor bearing mice. The enhanced antitumor effect and survival benefits endowed by the Au-Hb@PLT were confirmed and . These results demonstrate that these Au-Hb@PLT can work as an oxygen vehicle, offer a promising approach to mitigate hypoxia and improve RT efficacy with a low RT dosage.

摘要

放射治疗(RT)是一种广泛探索的临床方法,用于对抗癌症。然而,由于实体瘤中严重的缺氧微环境和对相邻健康组织有高剂量辐射的危害,其治疗效果并不总是令人满意。在此,制备了负载金纳米粒子-血红蛋白复合物的血小板(Au-Hb@PLT)。这些 Au-Hb@PLT 会被肿瘤细胞激活,形成的血小板衍生颗粒(PM)由于其体积小和肿瘤归巢能力,能够将金纳米粒子-血红蛋白复合物深入递送到肿瘤组织中。血红蛋白作为氧载体缓解缺氧,金纳米粒子作为放射增敏剂增强肿瘤细胞对 X 射线的敏感性,从而提高荷瘤小鼠在低剂量 RT 下的治疗效果。Au-Hb@PLT 增强的抗肿瘤效果和生存获益得到了证实。这些结果表明,这些 Au-Hb@PLT 可以作为一种氧载体,提供了一种有前途的方法来减轻缺氧并提高放射治疗效果,同时降低放射治疗剂量。

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