Ionic liquid (IL)-loaded or metal ions-enriched nanoparticles have been witnessed to assist microwave ablation (MWA) and heighten heat utilization for tumor treatment, which, however, inevitably brings about cell dys-homeostasis and severely endangers normal cells or tissues. In this report, a nonionic MWA sensitizer that encapsulates ethyl formate (EF) and doxorubicin (DOX) in liposomes (EF-DOX-Lips) was constructed to reinforce MWA and combined therapy against incomplete MWA-induced tumor recurrence. EF in EF-DOX-Lips as the nonionic liquid can perform like IL to accelerate energy transformation from electromagnetic energy to heat for strengthening MWA. More significantly, EF metabolite, that is, ethanol, also enables chemical ablation, which further enhances MWA. As well, the EF gasification-enhanced lipid rupture and cavitation can promote DOX delivery into a liver tumor for magnifying MWA & chemotherapy combined therapy. By virtue of these contributions, this nonionic MWA nanosensitizer exerts robust antitumor effects to inhibit tumor proliferation and angiogenesis for repressing tumor growth and recurrence or metastasis via downregulating the Epha2 gene and unconventional PI3K/Akt & MAPK signal pathways that the incomplete MWA activated, which provides an avenue to elevate an MWA-based antitumor outcome.
Keywords: Cell dyshomeostasis; Ethyl formate metabolism; Incomplete microwave ablation (MWA); Nonionic MWA nanosensitizers; Physical & chemical ablation.