Mitochondria-Targeting Enhanced Phototherapy by Intrinsic Characteristics Engineered "One-for-All" Nanoparticles

ACS Appl Mater Interfaces. 2021 Aug 4;13(30):35568-35578. doi: 10.1021/acsami.1c10850. Epub 2021 Jul 21.

Abstract

Mitochondria-targeted synergistic therapy, including photothermal (PTT) and photodynamic therapy (PDT), has aroused wide attention due to the high sensitivity to reactive oxygen species (ROS) and heat shock of mitochondria. However, most of the developed nanosystems for the combinatorial functions require the integration of different components, such as photosensitizers and mitochondria-targeted molecules. Consequently, it indispensably requires sophisticated design and complex synthetic procedures. In this work, a well-designed Bi2S3-based nanoneedle, that localizes to mitochondria and produces extra ROS with inherent photothermal effect, was reported by doping of Fe (denoted as FeBS). The engineered intrinsic characteristics certify the capacity of such "one-for-all" nanosystems without additional molecules. The lipophilicity and surface positive charge are demonstrated as crucial factors for specifical mitochondria targeting. Significantly, Fe doping overcomes the disadvantage of the narrow band gap of Bi2S3 to prevent the fast recombination of electron-hole, hence resulting in the generation of ROS for PDT. The "one-for-all" nanoparticles integrate with mitochondria-targeting and synergistic effect of PDT and PTT, thus exhibit enhanced therapeutic effect and inhibit the growth of tumors observably. This strategy may open a new direction in designing the mitochondria-targeted materials and broadening the properties of inorganic semiconductor materials for satisfactory therapeutic outcomes.

Keywords: enhanced therapeutic effect; iron-doped Bi2S3; mitochondria-targeting; photodynamic therapy; photothermal therapy.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents / toxicity
  • Bismuth / chemistry
  • Female
  • HeLa Cells
  • Humans
  • Iron / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mitochondria / drug effects*
  • Nanoparticles / chemistry*
  • Neoplasms / drug therapy*
  • Photochemotherapy
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use*
  • Photosensitizing Agents / toxicity
  • Photothermal Therapy
  • Reactive Oxygen Species / metabolism
  • Sulfides / chemistry

Substances

  • Antineoplastic Agents
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • Sulfides
  • Iron
  • Bismuth
  • bismuth sulfide