A mitochondria-targeted molecular phototheranostic platform for NIR-II imaging-guided synergistic photothermal/photodynamic/immune therapy

J Nanobiotechnology. 2022 Nov 11;20(1):475. doi: 10.1186/s12951-022-01679-0.

Abstract

Phototherapy is a conducive and non-invasive strategy for cancer therapy under light irradiation. Inspiringly, fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds a great promise for imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. However, most phototherapeutics still face great challenges, including complicated synthesis of agents, potential biotoxicity and unsatisfied therapeutic outcomes. Herein, a near-infrared laser triggered molecular photosensitizer FEPT, modified with triphenylphosphine PEGylation (PEG2000-TPP), is developed for NIR-II imaging-guided mitochondria-targeting synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/immune therapy (IMT). The mitochondria-targeting photosensitizer FEPT can produce reactive oxygen species (ROS) and hyperpyrexia upon 808 nm laser irradiation, resulting in mitochondrial dysfunction and photo-induced apoptosis via caspase-3 pathway. Phototherapy-induced hyperthermia or ROS triggers the release of immunogenic intracellular substrates from dying tumor cells, thereby promoting the activation of antitumor immunity. Herein, this work provides a practicable strategy to develop a molecular phototheranostic platform for imaging-guided cancer therapy via mitochondria-targeting.

Keywords: Immunogenic cell death; Mitochondria-targeting; NIR-II imaging-guided; Photodynamic therapy; Photothermal therapy.

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Mitochondria / metabolism
  • Nanoparticles* / chemistry
  • Neoplasms* / diagnostic imaging
  • Neoplasms* / drug therapy
  • Optical Imaging
  • Photochemotherapy* / methods
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Phototherapy
  • Photothermal Therapy
  • Reactive Oxygen Species / metabolism

Substances

  • Photosensitizing Agents
  • Reactive Oxygen Species