Co-delivery of cisplatin and oleanolic acid by silica nanoparticles-enhanced apoptosis and reverse multidrug resistance in lung cancer

Kaohsiung J Med Sci. 2021 Jun;37(6):505-512. doi: 10.1002/kjm2.12365. Epub 2021 Feb 8.

Abstract

Multidrug resistance (MDR) of chemotherapy is one of the significant concerns in cancer therapy. Here in our study, cisplatin (DDP) and oleanolic acid (OA) were co-loaded in mesoporous silica nanoparticles (Nsi) to construct DDP/OA-Nsi and solve the DDP-resistance in lung cancer therapy. The cytotoxicity and apoptosis assays demonstrated that in DDP-resistant A549/DDP cells, the cytotoxicity of DDP/OA-Nsi was significantly higher than that of free DDP or DDP single delivery system (DDP-Nsi). The intracellular drug accumulation study revealed that the intracellular DDP concentration in the DDP/OA-Nsi group was also higher than that in free DDP and DDP-Nsi groups. In the A549/DDP xenograft tumor model, DDP/OA-Nsi showed the best anticancer effect. In summary, DDP/OA-Nsi was a promising drug delivery system to solve MDR in lung cancer therapy.

Keywords: cisplatin; lung cancer; oleanolic acid; silica nanoparticle.

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis*
  • Cell Proliferation / drug effects
  • Cisplatin / administration & dosage*
  • Drug Delivery Systems*
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / administration & dosage*
  • Neoplasm Transplantation
  • Oleanolic Acid / administration & dosage*
  • Silicon Dioxide / chemistry*
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology

Substances

  • Antineoplastic Agents
  • Tetrazolium Salts
  • Thiazoles
  • Oleanolic Acid
  • Silicon Dioxide
  • thiazolyl blue
  • Cisplatin