Double pH-sensitive nanotheranostics of polypeptide nanoparticle encapsulated BODIPY with both NIR activated fluorescence and enhanced photodynamic therapy

J Mater Chem B. 2021 Nov 3;9(42):8871-8881. doi: 10.1039/d1tb01768c.

Abstract

To achieve accurate fluorescence imaging-guided cancer therapy, intelligent systems with specific responsiveness to the tumor microenvironment need to be designed. Here, we have achieved both enhanced NIR fluorescence and photodynamic therapy by introducing a dimethylamino functional group in BODIPY dyes, which can be used as a pH sensor under acidic conditions by coordinating with the proton. At pH 7.4, the fluorescence is quenched due to the photo-induced electron transfer (PET) process. After the photosensitizer is protonated in tumor cell lysosomes (pH 4.0-5.5), the PET process is inhibited and the fluorophore emission capacity is restored (fluorescence enhancement up to 10-fold), resulting in near-infrared fluorescence with the OFF/ON transition inside the tumor and enhanced singlet oxygen production for lysosome targeting capability. Due to the substitution of heavy atom iodine, the compound has a high singlet oxygen quantum yield of 81.8% in dichloromethane. In addition, using a pH-sensitive amphiphilic polypeptide (POEGMA23-PE9) as a carrier to wrap the photosensitizer BDPI can release enough drug in the acidic environment (pH 5.5-6.5) of intracellular endosomes/lysosomes, which is conducive to more adequate interactions of the photosensitizer with H+ and more effective enhancement of fluorescence emission and 1O2 production, achieving precise fluorescence imaging capability and extremely low background toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Boron Compounds / chemistry
  • Boron Compounds / pharmacology*
  • Capsules / chemistry
  • Cell Proliferation / drug effects
  • Dimethylamines / chemistry
  • Dimethylamines / pharmacology
  • Drug Screening Assays, Antitumor
  • Fluorescence*
  • Humans
  • Hydrogen-Ion Concentration
  • Infrared Rays
  • Lysosomes / metabolism
  • Mice
  • Nanoparticles / chemistry*
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Photochemotherapy
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Theranostic Nanomedicine
  • Tumor Cells, Cultured

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Antineoplastic Agents
  • Boron Compounds
  • Capsules
  • Dimethylamines
  • Peptides
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • dimethylamine