使用载有金鸡纳霉素的NGR功能化脂质体调节肿瘤血管正常化,以增强癌症放疗的效果。
Modulating tumour vascular normalisation using triptolide-loaded NGR-functionalized liposomes for enhanced cancer radiotherapy.
发表日期:2023 Jan 04
作者:
Ying-Ying Xu, Yan-Hong Chen, Jie Jin, Yuan Yuan, Jin-Meng Li, Xin-Jun Cai, Ruo-Ying Zhang
来源:
JOURNAL OF LIPOSOME RESEARCH
摘要:
放射治疗是肿瘤治疗中有效的治疗方法。然而,肿瘤微环境的特性,包括缺氧、低 pH 值和间质液压力,会导致放射线耐药。为了提高放射治疗的抗肿瘤效果,研究表明可以采用抗血管生成治疗修复肿瘤血管的结构和功能缺陷,从而预防放射线耐药或药物输送效果不佳。在本研究中,我们制备了三七酸(TP)负载的阿斯纳-甘氨酸-精氨酸(NGR)肽偶联的 mPEG2000-DSPE-靶向脂质体(NGR-PEG-TP-LPs),以诱导肿瘤血管正常化,以增加肿瘤细胞对放射治疗的敏感性。此外,为了量化肿瘤血管正常化窗口期,评估了 NGR-PEG-TP-LPs 处理后肿瘤血管的结构和功能。然后,基于肿瘤血管正常化期窗口,评估了这些处理后放射治疗的抗肿瘤效果,采用 HCT116 移植荷瘤小鼠模型。所得结果表明,NGR-PEG-TP-LPs 能够调节肿瘤血管的正常化,增加肿瘤微环境的氧含量,增强放射治疗的疗效。此外,肝脏和肾脏毒性测试表明,NGR-PEG-TP-LPs 在癌症治疗中的应用是安全的。
Radiotherapy is an effective therapy in tumour treatment. However, the characteristics of the tumour microenvironment, including hypoxia, low pH, and interstitial fluid pressure bring about radioresistance. To improve the anti-tumour effect of radiotherapy, it has been demonstrated that antiangiogenic therapy can be employed to repair the structural and functional defects of tumour angiogenic vessels, thereby preventing radioresistance or poor therapeutic drug delivery. In this study, we prepared triptolide (TP)-loaded Asn-Gly-Arg (NGR) peptide conjugated mPEG2000-DSPE-targeted liposomes (NGR-PEG-TP-LPs) to induce tumour blood vessel normalisation, to the end of increasing the sensitivity of tumour cells to radiotherapy. Further, to quantify the tumour vessel normalisation window, the structure and functionality of tumour blood vessels post NGR-PEG-TP-LPs treatment were evaluated. Thereafter, the anti-tumour effect of radiotherapy following these treatments was evaluated using HCT116 xenograft-bearing mouse models based on the tumour vessel normalisation period window. The results obtained showed that NGR-PEG-TP-LPs could modulate tumour vascular normalisation to increase the oxygen content of the tumour microenvironment and enhance the efficacy of radiotherapy. Further, liver and kidney toxicity tests indicated that NGR-PEG-TP-LPs are safe for application in cancer treatment.