Sprayable hydrogel loaded with engineered fusion cellular vesicles for cancer recurrence suppression.

BACKGROUND

Surgical resection often leaves residual lesions that lead to tumor recurrence and high mortality across various cancer types, a challenge that is particularly pronounced in oral squamous cell carcinoma. Herein, we developed a sprayable hydrogel loaded with fusion cellular vesicles (Fus-CVs) and characterized its structural and mechanical properties for the prevention of postoperative tumor recurrence. Fus-CVs co‑express PD‑1 to engage PD‑L1 on tumor cells and CD36 to competitively bind oxidized lipids in the tumor microenvironment, thereby effectively reversing T cell exhaustion and restoring T cell effector function. Additionally, the sprayable hydrogel, formed by crosslinking sodium alginate (SA) with the ionic solution (calcium chloride, CaCl2; manganese chloride, MnCl2), enables sustained local delivery of Fus‑CVs to potentiate T cell‑mediated killing of residual tumor cells.

RESULTS

In vitro experiments and primary tumor model confirmed that Fus‑CVs specifically achieve dual targeting of PD-L1 on tumor cells and oxidized lipids in the tumor microenvironment, reverse T cell exhaustion and achieve combination therapy. In an established postoperative recurrence mouse model, the SA solution containing Fus-CVs and the ionic solution could be co-sprayed to rapidly form a conformal, uniform and stable layer on irregular tissue surfaces, enabling sustained local release of Fus-CVs and achieve effective tumor recurrence suppression.

CONCLUSION

Fus‑CVs-loaded sprayable hydrogel not only achieves dual functionality in immune checkpoint blockade and lipid metabolic regulation but also offers localized controlled release, and reduced systemic toxicity, thereby presenting a clinically translatable strategy for postoperative recurrence prevention.