PFP@PLGA/Cu12Sb4S13-mediated PTT ablates hepatocellular carcinoma by inhibiting the RAS/MAPK/MT-CO1 signaling pathway

Abstract

Hepatocellular carcinoma (HCC) is one of the most malignant tumors in the world, and patients with HCC face a poor prognosis. The conventional therapeutic strategies for HCC have undergone a challenge-riddled evolution owing to side effects and unsatisfactory efficacy. Here, aiming to provide a new method of HCC elimination, we formulated a novel multifunctional nanocapsule (PFP@PLGA/Cu12Sb4S13, PPCu) with applications in contrast-enhanced ultrasound imaging (CEUS) and photothermal therapy (PTT). These PPCu were successfully constructed with an average diameter of 346 nm (polydispersity index, PDI = 0.276). The reinforced contrast ratio of these PPCu was determined by CEUS, revealing their promising applications in image-guided monitoring of HCC treatment. Furthermore, the excellent photoabsorption and biocompatibility indicated by organ H&E staining indicated that PPCu meet quality expectations for use as photothermal transduction agent (PTA). PPCu treatment at 50 °C and higher temperatures efficiently repressed the proliferation, induced the apoptosis and decreased the motility of HCC cells. These effects might have been results of RAS/MAPK/MT-CO1 signaling pathway inhibition. In summary, PPCu were constructed to integrate CEUS and PTT successfully into therapy, which can lead to HCC elimination through RAS/MAPK/MT-CO1 signaling pathway repression.

Magnetic iron oxide nanoparticle-loaded hydrogels for photothermal therapy of cancer cells

“…Although surgery, chemotherapy, and radiotherapy are the mainstays of cancer treatment in the past, their limitations such as low specificity and high risk of recurrence, have forced researchers to divert their attention beyond these traditional treatments to explore more effective therapy ( Meng et al, 2020 ; Caballero et al, 2022 ). Photothermal therapy (PTT) is a very promising cancer treatment modality emerging in recent years ( Zhang et al, 2020 ; Dong et al, 2021 ). Utilizing photothermal converters to capture and transform external light, the local heat generated during PTT can induce intracellular protein denaturation and apoptosis.…”