Trauma-Responsive Scaffold Synchronizing Oncolysis Immunization and Inflammation Alleviation for Post-Operative Suppression of Cancer Metastasis.

Abstract

Tumor surgery can create an inflammatory trauma to aggravate residual tumor "seed" to colonize pre-metastatic niches (PMNs) "soil" at secondary sites, thereby promoting post-operative metastasis. However, two-pronged strategies for post-surgical elimination of asynchronous "seeds" and "soil" at different regions are currently lacking. Here, we have designed a hydrogel that can be injected into a resection cavity, where it immediately forms a scaffold and gradually degrades responding to enriched reactive oxygen species at adjacent trauma for local delivery and on-demand release of autologous cancer cells succumbing to oncolysis (ACCO) and anti-inflammatory agent. The autologous cell source self-provides a whole array of tumor-associated antigens, and the oncolysis orchestration of a subcellular cascade confers a self-adjuvanting property, together guaranteeing high immunogenicity of the ACCO vaccine that enables specific antitumor immunization. In parallel, inflammation alleviation exerted bidirectional functions to reshape the local immune landscape and resuscitate ACCO, leading to the eradication of residual tumor "seeds" while simultaneously intercepting the "seed-soil" crosstalk to normalize distant lung leading to regression of pre-existing PMN "soil". As a result, regional and metastatic recurrence were completely thwarted. Together, this framework synchronizing oncolysis immunization and inflammation alleviation provides an effective option for post-operative suppression of metastasis.