Modulating tumour vascular normalisation using triptolide-loaded NGR-functionalized liposomes for enhanced cancer radiotherapy

Abstract

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

Keywords:

• Liposome
• triptolide
• tumour vascular normalisation
• radiotherapy
• therapeutic window

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Natural Science Foundation of China [grant number 82003669], Natural Science Foundation of Zhejiang Province [grant number LYY18H300001], Chinese Medicine Science and Technology Plan of Zhejiang Province [grant number 2021ZB213], Zhejiang Medical and Health Science and Technology Plan [grant number 2020KY741], and Medical Promising Youngster of Hangzhou.