Systematic Investigation of Biocompatible Cationic Polymeric Nucleic Acid Carriers for Immunotherapy of Hepatocellular Carcinoma

SIMPLE SUMMARY: Immunotherapy, including adaptive and innate immunotherapy, exhibits promising future for the treatment of hepatocellular carcinoma. As a common tool for immunotherapy, the safe and efficient gene delivery turns to be especially important. Biocompatible polymers are a category of promising materials used in gene delivery, while there still lacks a comprehensive review article to discuss the updates on multiple disciplines covering biocompatible polymers, gene therapy, tumor immune microenvironment, and immunotherapy. This review is well-integrated with biocompatible polymers, nonviral gene therapy, and cancer immunotherapy. Our investigation will provide different perspective for the scientists focusing on the domains of biomaterials, gene therapy, and oncologists to move their research work forward. ABSTRACT: Hepatocellular carcinoma (HCC) is the third-largest cause of cancer death worldwide, while immunotherapy is rapidly being developed to fight HCC with great potential. Nucleic acid drugs are the most important modulators in HCC immunotherapy. To boost the efficacy of therapeutics and amplify the efficiency of genetic materials, biocompatible polymers are commonly used. However, under the strong need of a summary for current developments of biocompatible polymeric nucleic acid carriers for immunotherapy of HCC, there is rare review article specific to this topic to our best knowledge. In this article, we will discuss the current progress of immunotherapy for HCC, biocompatible cationic polymers (BCPs) as nucleic acid carriers used (or potential) to fight HCC, the roles of biocompatible polymeric carriers for nucleic acid delivery, and nucleic acid delivery by biocompatible polymers for immunotherapy. At the end, we will conclude the review and discuss future perspectives. This article discusses biocompatible polymeric nucleic acid carriers for immunotherapy of HCC from multidiscipline perspectives and provides a new insight in this domain. We believe this review will be interesting to polymer chemists, pharmacists, clinic doctors, and PhD students in related disciplines.