NIR-II AIE Liposomes for Boosting Type-I Photodynamic and Mild-Temperature Photothermal Therapy in Breast Cancer Treatment

Adv Mater. 2025 Jan;37(3):e2411133. doi: 10.1002/adma.202411133. Epub 2024 Nov 26.

Abstract

Phototheranositcs has recently aroused extreme attention due to its exceptional advantages. However, the poor photothernostic efficiency, limited penetration depth, strong oxygen-dependence, and inevitable damage to normal tissue of conventional photothernostic materials severely hindered their total theranostic efficacy. Herein, a series of near-infrared second (NIR-II) photosensitizers (PSs) featuring aggregation-induced emission (AIE), NIR-II fluorescence imaging (FLI), type I photodynamic therapy (PDT) and mild-temperature photothermal therapy (PTT) are constructed through dual-strategy methods combining donor group engineering and fluorination engineering. Profiting from sufficient molecular rotors and high electronegativity of fluorine, the developed 2-(2-((5-(4-((4-(diphenylamino)phenyl)(phenyl)amino)phenyl)thiophen-2-yl)methylene)-5,6-difluoro-3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (BTS-2F) and 2-(2-((5-(4-(bis(4-(diphenylamino)phenyl)amino)phenyl)thiophen-2-yl)methylene)-5,6-difluoro-3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (TTS-2F) are endowed with NIR-II AIE property, high radical reactive oxygen species (ROS) generation ability and mild-temperature photothermal conversion. Through thin film hydration method, the prepared BTS-2F and TTS-2F loaded liposomes exhibit significant NIR-II FLI and improved type-I PDT/mild-temperature PTT therapy under laser irradiation both in vitro and orthotopic 4T1 mice models.

Keywords: Second near‐infrared fluorescence imaging; Type I photodynamic therapy; aggregation‐induced emission; mild‐temperature photothermal therapy; phototheranostic.

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / therapy
  • Cell Line, Tumor
  • Female
  • Humans
  • Infrared Rays
  • Liposomes* / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Photochemotherapy* / methods
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / pharmacology
  • Photosensitizing Agents* / therapeutic use
  • Photothermal Therapy* / methods
  • Reactive Oxygen Species / metabolism
  • Temperature*

Substances

  • Liposomes
  • Photosensitizing Agents
  • Reactive Oxygen Species