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.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common type of malignant tumor and the second leading cause of cancer-related mortality of men worldwide [1], and HCC treatment has undergone a challenge-riddled evolution [2]
3.1 Preparation and characterization of a novel Photothermal therapy (PTT) agent To accomplish US imaging-guided PTT for HCC treatment, PFP@PLGA/Cu12Sb4S13 nanocapsules (PPCu) synthesis was realized through a double emulsion evaporation process, in which Cu12Sb4S13, PLGA and PFP were introduced to a reaction mixture in different steps
3.2 In vitro phase transition and contrast-enhanced ultrasound imaging (CEUS) of the PPCu To confirm the ability of PFP to undergo a phase transition from a liquid to gas state, PPCu stimulated by a low-intensity focused ultrasound (LIFU) instrument was observed under an optical microscope
Summary
Hepatocellular carcinoma (HCC) is the fifth most common type of malignant tumor and the second leading cause of cancer-related mortality of men worldwide [1], and HCC treatment has undergone a challenge-riddled evolution [2]. Compared with other PTAs, including carbon nanotubes, MoO3-x and Au clusters, Cu12Sb4S13 nanoparticles possess much higher light-harvesting ability. Cu12Sb4S13 nanoparticles were incorporated onto the surface of poly(lactic-co-glycolic acid), (PLGA, a polymer with excellent biocompatibility) nanocapsules, the center of which was loaded with perfluoropentane (PFP, a perfluorocarbon). Perfluorocarbons exhibit superb characteristics for achieving extremely high oxygen solubility and biocompatibility, are widely used in the clinic in contrast-enhanced ultrasound imaging (CEUS) and enhance the therapeutic efficacy of radiotherapy and photodynamic therapy [18, 19]. After PLGA encapsulation, the PPCu exhibit a preferable photothermal temperature with increasing light-harvesting ability and satisfactory biocompatibility
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
