Radiofrequency ablation (RFA) is a clinically adopted method to destruct solid tumors, but often incapable to completely ablate large tumors as well as those with multiple metastatic sites. Recently, ferroptosis featured in iron-mediated excessive peroxidation of polyunsaturated fatty acids (PUFAs) has recognized as a non-apoptotic pathway in regulating cell death and shown to be promising to eradicate those therapy-resistant cancer cells. Considering the large amounts of PUFAs (e.g. phospholipids) in the tumor debris produced during RFA, we thus hypothesize that the development of suitable formulations to induce continuous lipid peroxidation with the tumor debris as the PUFA source may be helpful to trigger ferroptosis and eradicate those residual tumor cells post RFA.
Recently, the research group of Prof. Zhuang Liu, collaborated with Assoc. Prof. Liangzhu Feng develops a CaCO3-assisted double emulsion method to encapsulate lipoxidase and hemin with PLGA copolymers. The obtained HLCaP nanoreactors (NRs) show pH-dependent catalytic capacity, with lipoxidase to induce continuous production of lipid hydroperoxides using cancer cell debris as the fuel, and hemin to subsequently trigger generation of abundant cytotoxic reactive oxygen species (ROS) from these lipid hydroperoxides. Upon being fixed inside the residual tumors post RFA, such HLCaP NRs could produce lipid ROS from tumor debris to trigger ferroptosis, and exhibit superior suppression effect on those residual tumors growing on both mice and rabbits. Moreover, ferroptosis triggered by HLCaP NRs post RFA could prime anti-tumor immunity to effectively suppress the growth of both residual and metastatic tumors, especially in combination with anti-PD-1 immunotherapy. This work highlights an innovative tumor debris fueled anti-tumor strategy by utilizing the tumor-killing HLCaP NRs prepared via our developed CaCO3-assisted double emulsion process. Such HLCaP NRs with the capability in effectively inducing lipid peroxidation from tumor debris could not only enhance the therapeutic outcome of RFA, but also act as an immunogenic nanomedicine to enable the synergistic combination of RFA with ICB immunotherapy.
The first author, Ms. Zhijuan Yang, is from FUNSOM, Soochow University.
Link to paper: https://www.nature.com/articles/s41467-021-24604-9
Link to Prof. Zhuang Liu's group: http://nano.suda.edu.cn/LZ/
Acknowledgement: This work was partially supported by the National Natural Science Foundation of China (51802209, 22077093, 52032008), the National Research Programs from Ministry of Science and Technology (MOST) of China (2016YFA0201200), the Natural Science Foundation of Jiangsu Province (BK20180848), the Jiangsu Social Development Project (BE2019658), the Collaborative Innovation Center of Suzhou Nano Science and Technology, and the 111 Program from the Ministry of Education of China.
Editor: Danting Xiang