X-ray-responsive polypeptide nanogel for concurrent chemoradiotherapy

Juan Wang; Weiguo Xu; Ning Zhang; Changsheng Yang; Hengwei Xu; Zhongtang Wang; Baosheng Li; Jianxun Ding; Xuesi Chen

doi:10.1016/j.jconrel.2021.02.003

X-ray-responsive polypeptide nanogel for concurrent chemoradiotherapy

J Control Release. 2021 Apr 10:332:1-9. doi: 10.1016/j.jconrel.2021.02.003. Epub 2021 Feb 6.

Authors

Juan Wang¹, Weiguo Xu², Ning Zhang³, Changsheng Yang⁴, Hengwei Xu⁴, Zhongtang Wang⁴, Baosheng Li⁵, Jianxun Ding⁶, Xuesi Chen²

Affiliations

¹ Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Ji'nan 250117, PR China; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China.
² Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China.
³ Department of Foot and Ankle Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Ji'nan 250033, PR China.
⁴ Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Ji'nan 250117, PR China.
⁵ Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Ji'nan 250117, PR China. Electronic address: bsli@sdfmu.edu.cn.
⁶ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China. Electronic address: jxding@ciac.ac.cn.

PMID: 33561483
DOI: 10.1016/j.jconrel.2021.02.003

Abstract

Concurrent chemoradiotherapy (CCRT) is a standard treatment regimen for medically inoperable stage III non-small-cell lung carcinoma (NSCLC) owing to its superior prognostics compared with the sequential modality. Nevertheless, the current pattern of CCRT still fails to provide satisfactory survival outcome. Furthermore, CCRT is always accompanied by a higher risk of severe side effects, limiting the dose escalation. Herein, an X-ray-responsive polypeptide nanogel (PNG) was developed for on-demand delivery of chemotherapeutic agent triggered by radiotherapy to synergistically improve the efficacy of CCRT with reduced side effects. The smart PNG was formed by crosslinking methoxy poly(ethylene glycol)-block-poly(L-glutamic acid-co-γ-2-chloroethyl-L-glutamate) (mPEG-b-P(LG-co-CELG)) with a diselenide (Se-Se) bond. The doxorubicin (DOX)-loaded polypeptide nanogel (PNG/DOX) exhibited accelerated drug release when exposed to X-ray irradiation as a result of Se-Se bond degradation. With prolonged circulation and enhanced intratumoral accumulation in vivo, PNG/DOX combined with X-ray irradiation exhibited better synergistic antitumor efficacy and fewer side effects toward human A549 lung carcinoma-bearing nude mice. The smart X-ray-responsive nanogel provides a promising bridge between chemotherapy and radiotherapy and enhances the potential application of CCRT in clinic.

Keywords: Cancer therapy; Chemoradiotherapy; Diselenide bond; Polypeptide nanogel; X-ray-responsiveness.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Non-Small-Cell Lung* / drug therapy
Chemoradiotherapy
Doxorubicin / therapeutic use
Lung Neoplasms* / drug therapy
Mice
Mice, Nude
Nanogels
Peptides / therapeutic use
Polyethylene Glycols / therapeutic use
X-Rays

Substances

Nanogels
Peptides
Polyethylene Glycols
Doxorubicin