Multimodal Mesoporous Silica Nanocarriers for Dual Stimuli-Responsive Drug Release and Excellent Photothermal Ablation of Cancer Cells

Int J Nanomedicine. 2020 Oct 8;15:7667-7685. doi: 10.2147/IJN.S254344. eCollection 2020.

Abstract

Background: Core-shell types of mesoporous silica nanoparticles (MSNs) with multimodal functionalities were developed for bio-imaging, controlled drug release associated with external pH, and near-infrared radiation (NIR) stimuli, and targeted and effective chemo-photothermal therapeutics.

Materials and methods: We synthesized and developed a core-shell type of mesoporous silica nanocarriers for fluorescent imaging, stimuli-responsive drug release, magnetic separation, antibody targeting, and chemo-photothermal therapeutics. Also, the biocompatibility, cellular uptake, cytotoxicity, and photothermal therapy on these FS3-based nanocarriers were systematically investigated.

Results: Magnetic mesoporous silica nanoparticles was prepared by coating a Fe3O4 core with a mesoporous silica shell, followed by grafting with fluorescent conjugates, so-called FS3. The resulting FM3 was preloaded with therapeutic cisplatin and coated with polydopamine layer, so-called FS3P/C. Eventually, graphene oxide-wrapped FS3P/C (FS3P-G/C) exhibited high sensitivity in the dual stimuli (pH, NIR)-responsive controlled release behavior. On the other hand, Au NPs-coated FS3P/C (FS3P-A/C) exhibited more stable release behavior, irrespective of pH changes, and exhibited much more enhanced release rate under the same NIR irradiation. Notably, FS3P-A/C showed strong NIR absorption, enabling photothermal destruction of HeLa cells by its chemo-photothermal therapeutic effects under NIR irradiation (808 nm, 1.5 W/cm2). The selective uptake of FS3-based nanocarriers was confirmed in cancer cell lines including HeLa (American Type Culture Collection - ATCC) and SHSY5Y (ATCC 2266) by the images obtained from confocal laser scanning microscopy, flow cytometry, and transmission electron microscopy instruments. Cisplatin-free FS3-based nanocarriers revealed good cellular uptake and low cytotoxicity against cancerous HeLa and SH-SY5Y cells, but showed no obvious toxicity to normal HEK293 (ATCC 1573) cell.

Conclusion: Along with the facile synthesis of FS3-based nanocarriers, the integration of all these strategies into one single unit will be a prospective candidate for biomedical applications, especially in chemo-photothermal therapeutics, targeted delivery, and stimuli-responsive controlled drug release against multiple cancer cell types.

Keywords: Au NPs; cancerous cells; chemo-photothermal therapy; mesoporous silica NPs; stimuli-responsive drug release.

MeSH terms

  • Cisplatin
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry*
  • Drug Liberation*
  • Ferric Compounds / chemistry
  • Graphite / chemistry
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Hyperthermia, Induced*
  • Indoles / chemistry
  • Nanoparticles / chemistry*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Phototherapy*
  • Polymers / chemistry
  • Porosity
  • Silicon Dioxide / chemistry*

Substances

  • Drug Carriers
  • Ferric Compounds
  • Indoles
  • Polymers
  • graphene oxide
  • polydopamine
  • ferric oxide
  • Silicon Dioxide
  • Graphite
  • Doxorubicin
  • Cisplatin

Grant support

This study was supported financially by the Korea Institute of Energy Technology Evaluation and Planning (KETEP) and the Ministry of Trade, Industry, and Energy (MOTIE) of the Republic of Korea [grant no. 20194030202440] and the National Research Foundation of Korea (NRF-2020R1A2B5B01002463).