Physical & Chemical Microwave Ablation (MWA) Enabled by Nonionic MWA Nanosensitizers Repress Incomplete MWA-Arised Liver Tumor Recurrence

Abstract

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.

Rational Nanomedicine Design Enhances Clinically Physical Treatment‐Inspired or Combined Immunotherapy

“…[150] Several results were obtained, for example, 1) The TAAs for specifically activating T cell responses were enhanced after MWA. 2) After MWA, the activated T cells and B [156] Copyright 2022, American Chemical Society. d) The schematic image of MWA in combination with nanoparticles (MAN-DCs) for activating the anti-tumor immune response in vivo.…”

“…Reproduced with permission. [ 156 ] Copyright 2022, American Chemical Society. d) The schematic image of MWA in combination with nanoparticles (MAN‐DCs) for activating the anti‐tumor immune response in vivo.…”

“…[153][154][155] To overcome the shortcomings of current exogeneous cavitation nuclei and metal-based nanoparticles for enhancing MWA, that is, uncontrollable and nonpersistent enhancement actions and inevitable ion disruption-enabled dyshomeostasis of normal tissues, respectively, biocompatible non-ionic MWA nanosensitizers were constructed. [156] In this non-ionic MWA nanosensitizer, polar but non-ionic ethyl formate (EF) molecules as the liquid inner core were successfully loaded in liposomes along with doxorubicin (DOX). EF with high volatility could realize three enhancement actions (Figure 9a), that is, EF bubbles-mediated cavitation, polar oscillation-mediated electricity-heat energy conversion, and EF metabolism-enabled chemical ablation after degradation into ethanol.…”

Advances in nanobiotechnology-propelled multidrug resistance circumvention of cancer

“…Moreover, liposomes are the natural thermal-sensitive carriers that can respond to exogenous heat triggers and induce structural deformation to release drugs or cargoes. 118…”

“…Moreover, liposomes are the natural thermal-sensitive carriers that can respond to exogenous heat triggers and induce structural deformation to release drugs or cargoes. 118 Combinations with multiple stimuli-responsive nanocarriers Many researchers have reported the combined application of the above-mentioned stimuli-responsive nanocarriers. Wang et al proposed a systematic combinatorial strategy to overcome cisplatin resistance by triggering hyperthermia with NIR light.…”