Ultrasound-triggered endogenous tumor vaccination for the inhibition of metastasis and recurrence

Colorectal cancer is the third most common malignancy worldwide and the second leading cause of cancer-related mortality, with metastasis and recurrence remaining major clinical challenges. To address this, an injectable sodium alginate‑manganese-chlorin e6 (ALG-Mn-Ce6) hydrogel is developed to generate an endogenous tumor vaccine upon ultrasound (US) activation. In this process, Ce6-mediated sonodynamic therapy together with Mn 2+ -mediated chemodynamic effects efficiently generate reactive oxygen species (ROS), inducing immunogenic cell death (ICD) of tumor cells and promoting the release of damage-associated molecular patterns (DAMPs), thereby initiating in situ endogenous tumor vaccination. Meanwhile, Mn 2+ functions as an immune adjuvant by activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, further amplifying antitumor immune responses and significantly enhancing vaccine efficacy. In mouse models of colorectal cancer with lung metastasis and recurrence, US-triggered ALG-Mn-Ce6 hydrogel significantly suppresses primary tumor growth and metastasis, and prevents recurrence. Moreover, this hydrogel offers facile preparation, low cost, good scalability, superior injectability, and excellent safety. Collectively, this US-triggered injectable hydrogel-based endogenous tumor vaccine provides a promising therapeutic strategy for colorectal cancer and other solid tumors.