AUTHOR=Li Zhongxian , Xiang Jiawei , Zhang Qiang , Zhao Mingyuan , Meng Yuan , Zhong Jie , Li Tingting , Jia Lanxin , Li Kai , Lu Xi , Ao Zhuo , Han Dong TITLE=An engineered hydrogel with low-dose antitumor drugs enhances tumor immunotherapy through tumor interstitial wrap JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.1072393 DOI=10.3389/fbioe.2022.1072393 ISSN=2296-4185 ABSTRACT=

Stimulating immunogenic cell death (ICD) is the key to tumor immunotherapy. However, traditional chemoradiotherapy has limited effect on stimulating immunity and often requires repeated administration, which greatly reduces the tumor-killing effect. In this article, we created a sodium alginate hydrogel sustained-release system containing low-dose doxorubicin (Dox) and immune adjuvant R837, which were injected into the interstitial space to wrap around the tumor in situ, achieving a sustained release and long-lasting immune response. Cooperating with immune checkpoint blockade, Dox induced ICD, activated dendritic cells (DCs) and converted immunosuppressive M2-type tumor-associated macrophages (TAM) to tumor-killing M1-type TAMs. Simultaneously, it greatly promoted T cell proliferation and infiltration, and reduced tumor immunosuppressive factors, triggering a robust immune response to suppress tumors in vivo. In conclusion, this anti-tumor strategy based on interstitial injection can achieve continuous local immune stimulation by low-dose chemotherapy drugs, providing a potential approach for tumor immunotherapy.