Nitric oxide polymersome-immobilized hydrogels for prevention of post-surgical tumor recurrence and metastasis

Surgical resection is the primary means of tumor treatment. However, postoperative tumors are prone to recurrence and metastasis due to residual tumor cells and complicated post-surgical microenvironments. The absence of effective intervention strategies for regulating the recurrent tumor microenvironment frequently leads to unfavorable prognostic outcomes. To address this issue, a biodegradable nitric oxide donor (NO) polymersome-immobilized hydrogel platform (NO-GEL) was constructed by using biodegradable functional polycarbonates. The polymersomes from NO-GEL were utilized to load immune checkpoint inhibitors of anti-programmed cell death protein 1 antibody (αPD1) for synergistic postoperative cancer therapy. The αPD1-loaded NO-GEL (NO-GEL@αPD1) was characterized with reduction-responsive NO and αPD1 release in the emergence of recurrent tumor exhibiting gas/immunotherapeutic activity via NO-mediated microenvironment reprogramming and immune checkpoint blocking. More importantly, covalent-embedded polymersomes in the hydrogel prevented the endocytosis of αPD1 and increased the therapeutic efficiency for cell membrane target inhibition. The hybrid structure further avoided the sudden release of cargos and realized the on-demand release of bioactive agents when exposed to recurrent tumor cells. The in vivo results demonstrated that the platform could effectively inhibit tumor recurrence and metastasis on mouse models, suggesting a high potential for the combined treatment of postoperative tumor recurrence and metastasis.