Highly biocompatible thermosensitive nanocomposite gel for combined therapy of hepatocellular carcinoma via the enhancement of mitochondria related apoptosis

Nanomedicine. 2019 Oct:21:102062. doi: 10.1016/j.nano.2019.102062. Epub 2019 Jul 23.

Abstract

Primary hepatocellular carcinoma (HCC) is a common malignant tumor. Surgery is the main treatment, but HCC patients have a potential risk of tumor recurrence. Besides, many limitations arise during the application of single first-line antitumor drugs. Here, we selected Pluronic F-127 and sodium alginate (SA) to prepare a thermosensitive gel (Gel). The optimal synergistic ratio of PTX and DOX on the SMMC-7721 cells was 1: 2 (w/w), calculated by the Chou-Talalay analysis. Then, PTX and DOX coloaded liposomes (PD-LPs) with such drugs ratios presented enhanced anticancer ability in vitro. Upon local injection, the PD-LPs Gel formed a nanoparticles reservoir at tumor via sol-gel transformation, while exhibiting a long-term effective anti-tumor ability in vivo. The relative tumor volume after the PD-LPs Gel treatment was reduced over 62%. Effective mitochondria related apoptosis induction was observed. Therefore, the local delivery of PD-LPs Gel can be a promising alternative method for the HCC therapy.

Keywords: Combined therapy; Hepatocellular carcinoma; Mitochondria apoptosis; Thermosensitive gel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacokinetics
  • Doxorubicin* / pharmacology
  • Humans
  • Liposomes
  • Liver Neoplasms, Experimental* / drug therapy
  • Liver Neoplasms, Experimental* / metabolism
  • Liver Neoplasms, Experimental* / pathology
  • Mice
  • Mitochondria, Liver* / metabolism
  • Mitochondria, Liver* / pathology
  • Nanocomposites* / chemistry
  • Nanocomposites* / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Liposomes
  • Doxorubicin