Redox-responsive FRET-based polymer dot with BODIPY for fluorescence imaging-guided chemotherapy of tumor

Eur J Pharm Biopharm. 2018 Nov:132:200-210. doi: 10.1016/j.ejpb.2018.09.025. Epub 2018 Sep 26.

Abstract

Redox-responsive polymer dot (PD) were synthesized from disulfide cross-linked polymers in a carbonized process to allow quenching effects by loading of boron-dipyrromethene (BODIPY) onto the matrix. The disulfide linkage facilitated degradation of the PD system by intracellular glutathione (GSH), leading to fluorescence recovery by BODIPY and intracellular drug release. The paclitaxel release profile showed that approximately 100% of the drug escaped from the matrix in response to 10 mM GSH, whereas less than 10% was released in the absence of GSH. In vitro studies showed that quenching produced by BODIPY loading enabled visual monitoring of cancer cell death, as the quenching disappeared when BODIPY was released by GSH inside of cancer cells. The PD contain disulfide bonds representing a GSH-triggered ligand; thus, nanocarriers presented enhanced in vivo chemotherapeutic inhibition in xenograft tumor-bearing mice localized at the cancer location, guided by fluorescent off-on system tracking and measured by the release of BODIPY. This platform reacts to the redox level in sensitive manner and cancer cell death can be monitored by fluorescence, making this platform useful for bio-applications, particularly in vitro and in vivo therapy and diagnosis, while considering the cell physiological environment. This system may be useful for wider medical applications.

Keywords: FRET effect; Fluorescent off-on; Paclitaxel; Polymer dot; Redox-responsive.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Boron Compounds / chemistry
  • Cell Line, Tumor
  • Dogs
  • Drug Carriers / chemistry
  • Drug Liberation
  • Fluorescence Resonance Energy Transfer / methods
  • Glutathione / metabolism
  • Humans
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles
  • Neoplasms / drug therapy*
  • Oxidation-Reduction
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Polymers / chemistry*
  • Xenograft Model Antitumor Assays

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Antineoplastic Agents, Phytogenic
  • Boron Compounds
  • Drug Carriers
  • Polymers
  • Glutathione
  • Paclitaxel