A molybdenum oxide-based degradable nanosheet for combined chemo-photothermal therapy to improve tumor immunosuppression and suppress distant tumors and lung metastases

J Nanobiotechnology. 2021 Dec 19;19(1):428. doi: 10.1186/s12951-021-01162-2.

Abstract

Molybdenum oxide (MoOx) nanosheets have drawn increasing attention for minimally invasive cancer treatments but still face great challenges, including complex modifications and the lack of efficient accumulation in tumor. In this work, a novel multifunctional degradable FA-BSA-PEG/MoOx nanosheet was fabricated (LA-PEG and FA-BSA dual modified MoOx): the synergistic effect of PEG and BSA endows the nanosheet with excellent stability and compatibility; the FA, a targeting ligand, facilitates the accumulation of nanosheets in the tumor. In addition, DTX, a model drug for breast cancer treatment, was loaded (76.49%, 1.5 times the carrier weight) in the nanosheets for in vitro and in vivo antitumor evaluation. The results revealed that the FA-BSA-PEG/MoOx@DTX nanosheets combined photothermal and chemotherapy could not only inhibit the primary tumor growth but also suppress the distant tumor growth (inhibition rate: 51.7%) and lung metastasis (inhibition rate: 93.6%), which is far more effective compared to the commercial Taxotere®. Exploration of the molecular mechanism showed that in vivo immune response induced an increase in positive immune responders, suppressed negative immune suppressors, and established an inflammatory tumor immune environment, which co-contributes towards effective suppression of tumor and lung metastasis. Our experiments demonstrated that this novel multifunctional nanosheet is a promising platform for combined chemo-photothermal therapy.

Keywords: Distant tumor and lung metastasis; Meliorate tumor immunosuppression; Molybdenum oxide nanosheet; Photothermal and chemotherapy.

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / pharmacokinetics
  • Biocompatible Materials / pharmacology
  • Biocompatible Materials / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Female
  • Folic Acid / chemistry
  • Humans
  • Hyperthermia, Induced
  • Infrared Rays
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy
  • Mice
  • Mice, Inbred BALB C
  • Molybdenum / chemistry*
  • Nanostructures / chemistry
  • Nanostructures / therapeutic use*
  • Nanostructures / toxicity
  • Oxides / chemistry*
  • Polyethylene Glycols / chemistry
  • Serum Albumin, Bovine / chemistry
  • Thioctic Acid / chemistry
  • Tissue Distribution

Substances

  • Biocompatible Materials
  • Oxides
  • molybdenum trioxide
  • Serum Albumin, Bovine
  • Polyethylene Glycols
  • Thioctic Acid
  • Doxorubicin
  • Molybdenum
  • Folic Acid