Thermogel Delivers Oxaliplatin and Alendronate in situ for Synergistic Osteosarcoma Therapy

Yifu Sun; Ke Li; Chen Li; Ying Zhang; Duoyi Zhao

doi:10.3389/fbioe.2020.573962

Thermogel Delivers Oxaliplatin and Alendronate in situ for Synergistic Osteosarcoma Therapy

Front Bioeng Biotechnol. 2020 Sep 15:8:573962. doi: 10.3389/fbioe.2020.573962. eCollection 2020.

Authors

Yifu Sun¹, Ke Li², Chen Li¹, Ying Zhang³, Duoyi Zhao²

Affiliations

¹ Department of Orthopedics, The Second Hospital of Jilin University, Changchun, China.
² Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
³ Department of Orthopedics, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China.

Abstract

The therapeutic effect of osteosarcoma (OS) has not made extraordinary progress in the past few decades. Oxaliplatin (OXA) is a widely used clinical anti-tumor drug. Recent studies have shown that OXA can trigger anti-tumor immunity by inducing immunogenic death (ICD). Alendronate (ALN) has been used to threaten the skeletal system tumors because of the unique bone affinity and the ability to inhibit bone destruction. In this study, we co-loaded OXA and ALN on mPEG45-PLV19 thermo-sensitive hydrogel to perform in situ treatment on the mouse OS model. Slowly released OXA can induce immunogenic death of tumor cells. At the same time, thermo-sensitive hydrogels can induce the accumulation of cytotoxic T lymphocytes. Besides, ALN could synergistically diminish tumors and prevent bone destruction. This system could synergistically inhibit the progression of OS and lung metastasis and has no toxicity to various organs throughout the body.

Keywords: alendronate; immune activation; osteosarcoma therapy; oxaliplatin; thermo-sensitive hydrogel.