A sonosensitiser-based polymeric nanoplatform for chemo-sonodynamic combination therapy of lung cancer

J Nanobiotechnology. 2021 Feb 25;19(1):57. doi: 10.1186/s12951-021-00804-9.

Abstract

Background: Lung cancer is the most common type of tumour worldwide. Its relative lethality is considerably high. However, since the tumour tissues are located deep within the human body, traditional technologies, such as photodynamic therapy, do not have the desired effect. Sonosensitisers can penetrate deeply into tissues, and sonodynamic therapy (SDT) effectively inhibits tumours by generating reactive oxygen species. Ultrasound can also penetrate deeply, with a favourable tumour inhibition effect.

Results: A redox/ultrasound-responsive Rhein-chondroitin sulphate-based nano-preparation encapsulating docetaxel was fabricated. The nanoparticles displayed increased cellular uptake with quick drug release, good stability, and a monodispersed form in the physiological environment. Rhein induced apoptosis and altered mitochondrial membrane potential, which enhanced the expression of apoptosis-related proteins. SDT inhibited the metastasis and angiogenesis of cancer cells and activated anti-tumour capacity by reducing the expression of M2 macrophages.

Conclusions: The potential of Rhein for SDT was demonstrated. Production of reaction oxygen species was markedly enhanced after ultrasound treatment. The nanoplatform enhanced the synergistic anti-tumour effects of SDT and chemotherapeutic efficacy. The approach was biocompatibility. The findings could inform investigations of chemo-SDT for different cancers.

Keywords: Chemo-sonodynamic therapy; Macrophages; Reactive oxygen species; Redox/ultrasound-responsive; Rhein.

MeSH terms

  • A549 Cells
  • Anthraquinones
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Combined Modality Therapy / methods*
  • Docetaxel / pharmacology
  • Drug Liberation
  • Drug Therapy / methods*
  • Drug Therapy, Combination
  • Humans
  • Lung Neoplasms / drug therapy*
  • Macrophages / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Nanoparticles
  • Polymers / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Ultrasonic Therapy / methods*

Substances

  • Anthraquinones
  • Polymers
  • Reactive Oxygen Species
  • Docetaxel
  • rhein