Reengineering of Donor-Acceptor-Donor Structured Near-Infrared II Aggregation-Induced Emission Luminogens for Starving-Photothermal Antitumor and Inhibition of Lung Metastasis

ACS Nano. 2024 Oct 29;18(43):30069-30083. doi: 10.1021/acsnano.4c11527. Epub 2024 Oct 18.

Abstract

Electron acceptor possessing strong electron-withdrawing ability and exceptional stability is crucial for developing donor-acceptor-donor (D-A-D) structured aggregation-induced emission luminogens (AIEgens) with second near-infrared (NIR-II) emission. Although 6,7-diphenyl-[1,2,5] thiadiazolo [3,4-g] quinoxaline (PTQ) and benzobisthiadiazole (BBT) are widely employed as NIR-II building blocks, they still suffer from limited electron-withdrawing capacity or inadequate chemo-stability under alkaline conditions. Herein, a boron difluoride formazanate (BFF) acceptor is utilized to construct NIR-II AIEgen, which exhibits a better overall performance in terms of NIR-II emission and chemo-stability compared to the PTQ- and BBT-derived fluorophores. With finely tuned intramolecular motions and strong D-A interaction strength, TPE-BFF simultaneously exhibits high molar extinction coefficient (ε= 4.31 × 104 M-1cm-1), strong NIR-II emission (Φ = 0.49%) and photothermal effect (η = 58.5%), as well as high stability. Thanks to these merits, the thermosensitive nanoparticles constructed by integrating TPE-BFF and the antiglycolytic agent 2-deoxy-d-glucose (2DG) are successfully utilized for imaging-guided photothermal antitumor lung metastasis by regulating glycolysis and reducing ATP-dependent heat shock proteins. Combining experimental results and theoretical calculations, BFF proves to be an outstanding electron acceptor for the design of versatile NIR-II AIEgens. Overall, this study offers a promising alternative for developing multifunctional NIR-II AIEgens in biomedical applications.

Keywords: NIR-II fluorescence; aggregation-induced emission; antitumor metastasis; donor−acceptor−donor; photothermal therapy.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Boron Compounds / chemistry
  • Boron Compounds / pharmacology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Fluorescent Dyes* / chemistry
  • Humans
  • Infrared Rays*
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Optical Imaging
  • Photothermal Therapy

Substances

  • Antineoplastic Agents
  • Fluorescent Dyes
  • Boron Compounds