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

  • Nano Converg. 2021 Oct 4;8(1):29. doi: 10.1186/s40580-021-00279-2.
Tianxiu Dong   #  1 ,  Jian Jiang   #  1 ,  Hao Zhang  1  2 ,  Hongyuan Liu  1 ,  Xiaomeng Zou  1 ,  Jiamei Niu  1 ,  Yingxuan Mao  1 ,  Mingwei Zhu  1 ,  Xi Chen  1 ,  Zizhuo Li  1 ,  Yaodong Chen  3 ,  Chunying Shi  4 ,  Xiuhua Yang  5
Affiliations
  • 1. Department of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
  • 2. Department of Medical Imaging, Heilongjiang Provincial Hospital, Harbin, 150001, China.
  • 3. Department of Ultrasonic Imaging, First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
  • 4. Department of Radiology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
  • 5. Department of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. [email protected].
  • # Contributed equally.
PMID: 34606010 DOI: 10.1186/s40580-021-00279-2
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.

Keywords
Hepatocellular carcinoma; Nanocapsule; Photothermal therapy; Thermal ablation.
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