Microwave ablation (MWA) is an interventional technique developed for local thermal ablation of tumors by using the heat generated by the intense oscillation of polar molecules under microwave exposure. Attributing to its minimal invasiveness, short-term clinical operation time, and highly effective cell killing capacity, MWA has currently been widely used for treating several types of solid tumors including hepatocellular carcinoma, pulmonary cancer, and colorectal cancer liver/pulmonary metastases. However, owing to the irregular shape of most tumors, current MWA treatment often needs to produce a larger ablation zone at a higher operation power density for complete tumor ablation and thereby would impose severe thermal damages to surrounding normal tissues with frequent side effects (e.g., post-ablation syndrome and pleural effusions). Therefore, it is of great significance to find out a type of functional agent that can confer current MWA with enhanced tumor heating efficacy in a tunable heating zone to realize more efficient MWA cancer treatment with superior safety.
Recently, Prof. Zhuang Liu and Assoc. Prof. Liangzhu Feng of our Insititue developed a metallo-alginate hydrogel with promising microwave susceptibility and immunostimulatory effect to potentiate MWA treatment. Attributing to the high loading capacity of alginate polymer to diverse divalent metal ions, traditional ALG hydrogel could be used as a concise platform to enable in situ fixation of different metal ions under the guidance of real-time imaging instruments (e.g., ultrasonography) for varying purposes. Using its tunable microwave susceptibility by adjusting the concentrations of free-standing Ca2+ ions and ALG, the in situ formed Ca2+-surplus ALG hydrogel could not only enable effective microwave heating at a significantly reduced power density but also concentrate the heat inside the injected zone, thereby showing great promise to reduce the side effects faced by the conventional MWA treatment. Together with the high potency of high extracellular Ca2+ exposure in enhancing the cell killing ability of the subtherapeutic hyperthermia by destructing intracellular Ca2+ homeostasis, our proposed ALG-Ca assisted MWA treatment could offer superior therapeutic efficacy. Furthermore, owing to the ability of extracellular Ca2+ in potentiating mild hyperthermia mediated release of diverse immunostimulatory DAMPs, this in situ formed Ca2+-surplus ALG hydrogel was found to be a potent adjuvant biomaterial to promote the maturation of DCs at a comparable immunostimulatory potency to commercial R837. Moreover, by virtue of the high capacity of ALG hydrogels in loading divalent metal ions (e.g., STING activating Mn2+), the simultaneous introduction of Mn2+ could further enhance the immunostimulatory capacity of MWA treatment by activating the STING pathway. Therelevant results were published online August 3, 2022 in Science Advances (Sci. Adv. 8, eabo5285 (2022)). PhD student Yujie zhu is the first author of this paper.
Link to paper: https://www.science.org/doi/10.1126/sciadv.abo5285
Title:Metallo-alginate hydrogel can potentiate microwave tumor ablation for synergistic cancer treatment
Authors:Yujie Zhu, Zhijuan Yang, Zijian Pan, Yu Hao, Chunjie Wang, Ziliang Dong, Quguang Li, Yikai Han, Longlong Tian, Liangzhu Feng*, Zhuang Liu*
Acknowledgement:This work was supported by the National Natural Science Foundation of China (22077093 and 52032008), National Research Programs from Ministry of Science and Technology (MOST) of China (2021YFF0701800), Jiangsu Social Development Project (BE2019658), Collaborative Innovation Center of Suzhou Nano Science and Technology, and Suzhou Key Laboratory of Nanotechnology and Biomedicine 111 Program from the Ministry of Education of China.
Editor: Guo Jia