Microwave ablation (MWA) is a minimally invasive cancer treatment that kills tumour cells using heat generated by exposure to microwave energy. MWA is currently used to treat several types of solid tumours, including hepatocellular carcinoma, pulmonary cancer, colorectal cancer liver and pulmonary metastases. But despite rapid advances in the field, the high powers needed to ablate a tumour can damage surrounding tissues, limiting MWA’s clinical application. As such, the use of additional functional agents to increase the tumour heating efficacy of MWA while sparing normal tissues has become a hot topic.
To address this problem, researchers from the Institute of Functional Nano & Soft Materials (FUNSOM), at Soochow University in China fabricated a sodium alginate hydrogel cross-linked with calcium ions to serve as a bifunctional material that enhances microwave ablation efficacy and stimulates anti-tumour immunity. They describe their findings in Science Advances.
High calcium concentration
Hydrogel in its native form is a highly absorbent, soluble polymer, and synthetic hydrogels are fast becoming attractive biomedical materials owing to their excellent biocompatibility with human cells and tissues. Previous research indicated that free-standing ions located inside the networks of hydrogel polymers can act as microwave-susceptible agents, because of the ion confinement effect within the gel layers. This finding suggests that hydrogels could be further adapted for MWA applications.
To achieve this, the researchers cross-linked sodium alginate (ALG) with calcium chloride (CaCl2) solution to form ALG-Ca hydrogels. By introducing a high concentration of calcium ions into the hydrogel network, they leveraged their oscillating properties under electromagnetic radiation to increase the efficiency of microwave heating.
The researchers evaluated the microwave susceptibility of these ALG-Ca hydrogels by recording temperature increases after microwave irradiation. They also tested the hydrogels’ ability to concentrate the heating zone, to ensure that the thermal energy is dissipated within the ablation target.
The microwave-sensitive ALG-hydrogel demonstrated excellent tunability. By adjusting the concentrations of calcium ions and ALG, the calcium ion-surplus ALG hydrogel not only enabled effective microwave heating at a significantly reduced power density, but also concentrated the heat inside the injection zone, thereby showing great promise for reducing the side effects of conventional MWA.
The team investigated the treatment efficacy of this calcium-infused hydrogel combined with MWA in several groups of tumour-bearing mice. Tumours in mice injected with the calcium-infused hydrogel and exposed to microwave energy were fully ablated compared with those in mice treated with plain hydrogel and microwaves. The ALG-Ca-treated mice also showed no noticeable tumour recurrence for up to 60 days. Similarly, rabbits with larger tumours showed improved tumour suppression after ALG-Ca injection and MWA.
Furthermore, the calcium-infused hydrogel generated a pro-inflammatory microenvironment that activates anti-tumour immunity in mice. This suggests that the ALG-Ca hydrogel may also act as an immunostimulatory biomaterial to promote the maturation of dendritic cells – specialized cells that boost immune response – with comparable potency to a commercial immune boosting agent.
Principal author Zhuang Liu, head of FUNSOM’s Laboratory of Advanced Biomaterials and Nanomedicine, says that the metallo-alginate hydrogel holds great promise for future clinical translation to extend the clinical applications of MWA.
