Pluronic F127-functionalized molybdenum oxide nanosheets with pH-dependent degradability for chemo-photothermal cancer therapy

J Colloid Interface Sci. 2019 Oct 1:553:567-580. doi: 10.1016/j.jcis.2019.06.066. Epub 2019 Jun 20.

Abstract

Traditional cancer therapies carry a risk of serious side effects and toxicity. Developing an alternative treatment modality that is highly effective, has low toxicity and is noninvasive is urgently required. Here, we exploited molybdenum oxide (MoOx) nanosheets as a drug carrier and degradable photothermal agent to provide a chemo-photothermal combination cancer therapy. The MoOx nanosheets were synthesized by a one-pot hydrothermal method and then modified with pluronic F127 to improve physiological stability and biocompatibility. The F127-modified nanosheets (MoOX@F127) showed ultrahigh drug loading efficiency (DLE) of doxorubicin (DOX) (DLE%; 65%, W(load DOX)/[W(load DOX) + WMoOx@F127]), strong near-infrared (NIR) absorption and desirable pH-dependent degradability. After intravenous injection, MoOx@F127 nanosheets were degraded at physiological pH and were rapidly excreted from normal organs, while they were effectively accumulated and retained long-term in the more acidic tumor tissue. This simultaneously ensured effective tumor ablation after NIR irradiation and avoided long-term retention and toxicity in vivo. Compared to chemotherapy or photothermal therapy alone, in vitro and in vivo tumor ablation studies have shown a notably improved synergistic effect of the combination therapy. Our study presents a multifunctional nanosystem with a desirable degradability for chemo-photothermal combination cancer therapy that has great potential in biomedical applications.

Keywords: Chemo-photothermal therapy; Inorganic therapeutic agents; Molybdenum oxide nanosheets; One-pot; pH-dependent degradation.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacology*
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • MCF-7 Cells
  • Male
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Molybdenum / administration & dosage
  • Molybdenum / chemistry
  • Nanoparticles / chemistry*
  • Oxides / administration & dosage
  • Oxides / chemistry
  • Particle Size
  • Phototherapy*
  • Poloxamer / administration & dosage
  • Poloxamer / chemistry
  • Rats
  • Rats, Wistar
  • Surface Properties
  • Tumor Cells, Cultured

Substances

  • Antibiotics, Antineoplastic
  • Oxides
  • Poloxamer
  • Doxorubicin
  • Molybdenum