Nanoplatform based on GSH-responsive mesoporous silica nanoparticles for cancer therapy and mitochondrial targeted imaging

Mikrochim Acta. 2021 Apr 6;188(5):154. doi: 10.1007/s00604-021-04810-4.

Abstract

Mitochondria, as the energy factory of most cells, are not only responsible for the generation of adenosine triphosphoric acid (ATP) but also essential targets for therapy and diagnosis of various diseases, especially cancer. The safe and potential nanoplatform which can deliver various therapeutic agents to cancer cells and mitochondrial targeted imaging is urgently required. Herein, Au nanoparticles (AuNPs), mesoporous silica nanoparticles (MSN), cationic ligand (triphenylphosphine (TPP)), doxorubicin (DOX), and carbon nanodots (CDs) were utilized to fabricate mitochondrial targeting drug delivery system (denoted as CDs(DOX)@MSN-TPP@AuNPs). Since AuNPs, as the gatekeepers, can be etched by intracellular glutathione (GSH) via ligand exchange induced etching process, DOX can be released into cells in a GSH-dependent manner which results in the superior GSH-modulated tumor inhibition activity. Moreover, after etching by GSH, the CDs(DOX)@MSN-TPP@AuNPs can serve as promising fluorescent probe (λex = 633 nm, λem = 650 nm) for targeted imaging of mitochondria in living cells with near-infrared fluorescence. The induction of apoptosis derived from the membrane depolarization of mitochondria is the primary anti-tumor route of CDs(DOX)@MSN-TPP@AuNPs. As a kind of GSH-responsive mitochondrial targeting nanoplatform, it holds great promising for effective cancer therapy and mitochondrial targeted imaging. The mitochondrial targeting drug delivery system was fabricated by AuNPs, MSN, TPP, and CDs. The nanoplatform can realize redox-responsive drug delivery and targeted imaging of mitochondria in living cells to improve the therapeutic efficiency and security.

Keywords: Carbon nanodots; Mitochondrial probe; Near-infrared fluorescence; Redox-sensitive drug delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carbon / chemistry
  • Carbon / toxicity
  • Cell Line, Tumor
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • Drug Liberation
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / toxicity
  • Glutathione / metabolism
  • Gold / chemistry
  • Gold / toxicity
  • Humans
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / toxicity
  • Mice
  • Mitochondria / metabolism*
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / toxicity
  • Quantum Dots / chemistry
  • Quantum Dots / toxicity
  • Silicon Dioxide / chemistry
  • Silicon Dioxide / toxicity
  • Silver / chemistry
  • Silver / toxicity

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Fluorescent Dyes
  • Organophosphorus Compounds
  • triphenylphosphine
  • Silver
  • Carbon
  • Gold
  • Silicon Dioxide
  • Doxorubicin
  • Glutathione