Thermogel Delivers Oxaliplatin and Alendronate in situ for Synergistic Osteosarcoma Therapy.

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

doi:10.3389/fbioe.2020.573962

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.

Highlights

Osteosarcoma (OS), as the highest incidence of malignant bone tumor, has been harmful to human health (Wang et al, 2020)
Lung metastasis is an essential factor of the poor prognosis of OS (Huang X. et al, 2019)
Researchers have found that some current chemotherapy drugs can induce immunogenic cell death (ICD) of tumor cells, and the mechanism is related to the induction to apoptosis, including the exposure of calreticulin (CRT) on the cell membrane (Sukkurwala et al, 2014)

Summary

Introduction

Osteosarcoma (OS), as the highest incidence of malignant bone tumor, has been harmful to human health (Wang et al, 2020). The standard treatment of OS includes neoadjuvant chemotherapy, surgical resection, and post-operative chemotherapy (Zhang et al, 2020). Despite the deepening of research in this field, there has been no significant improvement in patient survival in recent decades (Harrison et al, 2018). Immunotherapy has provided new directions for the treatment of cancer. Researchers have found that some current chemotherapy drugs can induce immunogenic cell death (ICD) of tumor cells, and the mechanism is related to the induction to apoptosis, including the exposure of calreticulin (CRT) on the cell membrane (Sukkurwala et al, 2014). Platinum drugs are the first-line chemotherapy drugs for the treatment of OS (Cheng et al, 2020). Oxaliplatin (OXA) is the third-generation platinum anti-tumor drug that

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