Heat and Heal: Microwave-Responsive Gelling Hydrogel Nanocomposites for Postablation Extracellular Matrix Normalization and Chemotherapy Sensitization

Microwave ablation (MWA) is minimally invasive tumor therapy using electromagnetic waves. Incomplete ablation due to tumor size, location, or suboptimal planning often causes recurrence and metastasis. Although adjuvant chemotherapy can mitigate relapse, its efficacy remains limited as MWA-induced tissue injury triggers abnormal angiogenesis and extracellular matrix (ECM) remodeling, thereby hindering drug penetration. Here, we propose a microwave-responsive gelling hydrogel nanocomposite that enhances heating of MWA and remodels the postablation microenvironment. The nanocomposite was prepared by dispersing polymeric nanoparticles, comprising a CaCl₂-rich core and a tranilast-loaded shell, into alginate solution. Under microwave irradiation, the polar salt core generated rapid heating, ruptured, and released calcium ions, which cross-linked alginate to form a stable hydrogel in situ. By integrating microwave sensitization with postablation microenvironment regulation, this strategy simultaneously resolves insufficient heating and aberrant ECM remodeling, enabling improved chemotherapeutic efficacy. This simple and biocompatible platform provides a rational approach for improving local tumor MWA and reducing postablation recurrence.