In situ engineered magnesium alloy implant for preventing postsurgical tumor recurrence

Invasive tumors are difficult to be completely resected in clinical surgery due to the lack of clear resection margins, which greatly increases the risk of postoperative recurrence. However, chemotherapy and radiotherapy as the traditional means of postoperative adjuvant therapy, are limited in postoperative applications, such as multi-drug resistance and low sensitivity, etc. Therefore, an engineered magnesium alloy rod is designed as a postoperative implant to completely remove postoperative residual tumor tissue and inhibit tumor recurrence by gas and mild magnetic hyperthermia therapy (MMHT). As a reactive metal, magnesium alloy responds to the acidic tumor microenvironment by continuously generating hydrogen. The in-situ generation of hydrogen not only protects the surrounding normal tissue, but also enables the magnesium alloy to achieve MMHT under low-intensity alternating magnetic field (AMF). Furthermore, the numerous reactive oxygen species (ROS) produced by heat stress will combine with nitric oxide (NO) generated in situ, to produce more toxic reactive nitrogen species (RNS) storm. In summary, engineered magnesium alloy can completely remove residual tumor tissue and inhibit tumor recurrence by MMHT and RNS storm under low-intensity AMF, and the biodegradability of magnesium alloy makes great potential for clinical application. A postoperatively implanted surface-modified magnesium alloy rod (MgA@MgO 2 @BSA@PL-Arg, MMBP) generates hydrogen gas and nitric oxide in situ. In addition, under an alternating magnetic field, MMBP enables mild magnetic hyperthermia/combination gas therapy and generates a large amount of RNS, thus effectively inhibiting tumor recurrence after surgery. • MMBP protects the surrounding normal tissue while inhibiting tumor recurrence. • MMBP produced RNS storm in situ and successfully inhibited tumor recurrence. • MMBP can be safely and slowly degraded in vivo without secondary surgical removal, making it an ideal postoperative implant.