Three birds with one stone: co-encapsulation of diclofenac and DL-menthol for realizing enhanced energy deposition, glycolysis inhibition and anti-inflammation in HIFU surgery

Abstract

Despite attracting increasing attention in clinic, non-invasive high-intensity focused ultrasound (HIFU) surgery still commonly suffers from tumor recurrence and even matastasis due to the generation of thermo-resistance in non-apoptotic tumor cells and adverse therapy-induced inflammation with enhanced secretion of growth factors in irradiated region. In this work, inspired by the intrinsic property that the expression of thermo-resistant heat shock proteins (HSPs) is highly dependent with adenosine triphosphate (ATP), dual-functionalized diclofenac (DC) with anti-inflammation and glycolysis-inhibition abilities was successfully co-encapsulated with phase-change dl-menthol (DLM) in poly(lactic-co-glycolic acid) nanoparticles (DC/DLM@PLGA NPs) to realize improved HIFU surgery without causing adverse inflammation. Both in vitro and in vivo studies demonstrated the great potential of DC/DLM@PLGA NPs for serving as an efficient synergistic agent for HIFU surgery, which can not only amplify HIFU ablation efficacy through DLM vaporization-induced energy deposition but also simultaneously sensitize tumor cells to hyperthermia by glycolysis inhibition as well as diminished inflammation. Thus, our study provides an efficient strategy for simultaneously improving the curative efficiency and diminishing the harmful inflammatory responses of clinical HIFU surgery. Graphical Abstract

Shikonin-Loaded Hollow Fe-MOF Nanoparticles for Enhanced Microwave Thermal Therapy

“…They revealed that lactate significantly declined along with ATP. Wu et al reported that inhibiting glycolysis can sensitize tumor cells to high-intensity focused ultrasound (HIFU) thermal therapy . The possible reason is that thermo-resistant heat shock proteins (HSPs) are downregulated, and the synthesis of HSPs is highly ATP-dependent.…”

“…As such, the cancer cells became more vulnerable and less tolerant to MW-mediated hyperthermia and dynamic therapy. A similar mechanism was proposed in a previous study by Wu et al The histological examination with H&E staining showed that the tumor death in the HFM@SK@HA + MW group was more radical as compared with the other treatment groups (Figure F). As displayed in Figure E, the weight change of mice in each group was not obvious.…”

A Self‐Delivery Nanodrug Simultaneously Inhibits COX‐2/PGE2 Mediated Inflammation and Downregulates PD‐L1 to Boost Photoimmunotherapy

“…The released DA inhibits COX-2 activity and blocks arachidonic acid conversion to PGE 2 . [39][40][41] Blocking the COX-2/PGE 2 pathway could both decrease pro-tumor inflammatory factors including IL-6 and TNF-𝛼 and further down-regulate the PD-L1 expression to reduce the tumor cells inhibition by cytotoxic T cells. In general, CCP@DA induced a strong ICD to activate anti-tumor immunity through targeted photothermal/photodynamic synergistic therapies on the tumor cell membrane.…”

A mitochondria targeted cascade reaction nanosystem for improved therapeutic effect by overcoming cellular resistance

“…In order to restrain glycolysis, the utilization of chemotherapy drugs has aroused great attention. 20,21 However, as mentioned above, there are numerous challenges faced by chemotherapy, such as MDR. Exceptionally, researchers have certified that although some glycolysis related proteins could be destroyed during the treatment, the mitochondria could also play a vital role in providing energy for cytoprotection.…”