Spatiotemporal combination of thermosensitive polypeptide fused interferon and temozolomide for post-surgical glioblastoma immunochemotherapy

Ping Liang; Guihuai Wang; Xinyu Liu; Zhuoran Wang; Jing Wang; Weiping Gao

doi:10.1016/j.biomaterials.2020.120447

Spatiotemporal combination of thermosensitive polypeptide fused interferon and temozolomide for post-surgical glioblastoma immunochemotherapy

Biomaterials. 2021 Jan:264:120447. doi: 10.1016/j.biomaterials.2020.120447. Epub 2020 Oct 10.

Authors

Ping Liang¹, Guihuai Wang¹, Xinyu Liu², Zhuoran Wang³, Jing Wang¹, Weiping Gao⁴

Affiliations

¹ Department of Neurosurgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, PR China.
² Department of Geriatric Dentistry, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, China; Biomedical Engineering Department, Peking University, Beijing, 100191, PR China.
³ CAS Engineering Laboratory for Nanozyme, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, PR China.
⁴ Department of Geriatric Dentistry, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, China; Biomedical Engineering Department, Peking University, Beijing, 100191, PR China. Electronic address: gaoweiping@hsc.pku.edu.cn.

PMID: 33069137
DOI: 10.1016/j.biomaterials.2020.120447

Abstract

Cancer recurrence post surgical resection is of considerable challenge especially in glioblastoma (GBM) therapy. Herein, we demonstrate that interferon-alpha (IFN) fused to a body temperature-sensitive elastin-like polypeptide (IFN-ELP(V)) formed a depot in situ when injected into GBM resection cavity in a mouse brain orthotopic model of GBM. Notably, IFN-ELP(V) in the depot showed a zero-order release kinetics, resulting in dramatically improved pharmacokinetics and biodistribution, and thus inhibited GBM recurrence by stimulating antitumor immunoresponse as compared to IFN. More importantly, when combined with subsequent intraperitoneal injection of temozolomide (TMZ), IFN-ELP(V) could much more effectively suppress post-surgical GBM recurrence than IFN, leading to a remarkably enhanced GBM-free survival rate (60%) over IFN (12.5%). Our findings implicate that the spatiotemporally-programmed combination of IFN-ELP(V) and TMZ leads to the synergy of post-surgical GBM immunochemotherapy, thereby providing a new and effective strategy for cancer therapy.

Keywords: Controlled release; Glioblastoma; Immunochemotherapy; Interferon; Polypeptide.

Publication types

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

MeSH terms

Animals
Brain Neoplasms* / drug therapy
Cell Line, Tumor
Drug Resistance, Neoplasm
Glioblastoma* / drug therapy
Mice
Neoplasm Recurrence, Local
Temozolomide / therapeutic use
Tissue Distribution
Xenograft Model Antitumor Assays

Substances

Temozolomide