Tumor vessel-adaptable adhesive and absorbable microspheres for sustainable transarterial chemoembolization therapy

Transarterial chemoembolization (TACE) is a common clinical intervention used for unresectable liver tumors, but conventional embolic microspheres generally exhibit slack vascular stacking and suboptimal drug release. Here, we report tumor vessel-adaptable, adhesive, and absorbable microspheres (3Asphere) based on hyaluronic acid developed using microfluidic and radical polymerization techniques for sustained TACE therapy of liver tumors. 3Asphere presents uniform sizes, gradual degradation over two months, and fast encapsulation and sustained release of chemotherapeutics such as epirubicin, irinotecan, and cisplatin. Interestingly, 3Asphere with high elasticity enables robust vascular embolization, effectively blocking rabbit renal blood supply for over one month. In rabbit VX2 orthotopic liver tumors, 3Asphere actively binds to endothelial cells via CD44 and inhibits tumor growth, affording significant survival benefits compared to commercial Embosphere^®. TACE with epirubicin-loaded 3Asphere further enhances tumor inhibition and prevents lung metastasis. 3Asphere provides a versatile and advanced TACE therapy that might alleviate liver tumors.