Targeted combinational therapy inducing mitochondrial dysfunction.
Weon Sup ShinSoon Ki ParkPeter VerwilstSeyoung KooJoung Hae LeeSung-Gil ChiJong Seung KimPublished in: Chemical communications (Cambridge, England) (2018)
We report on a mitochondria-specific combinational theranostic agent, 1. This system contains a chlorambucil prodrug and an aggregation induced emission dye. In addition, compound 1 bears both an intracellular thiol-triggered moiety and a mitochondria targeting unit (triphenylphosphonium). Glutathione (GSH) is the most abundant thiol and its concentrations are significantly higher in a great number of cancer cell lines, compared to normal cells. The GSH-induced prodrug 1 upon activation releases chlorambucil and exhibits mitochondria targeted aggregation induced emission (AIE) fluorescence, resulting in cell apoptosis via the caspase pathway due to mitochondrial dysfunction.
Keyphrases
- cancer therapy
- cell death
- reactive oxygen species
- cell cycle arrest
- induced apoptosis
- fluorescent probe
- drug delivery
- endoplasmic reticulum
- papillary thyroid
- living cells
- endoplasmic reticulum stress
- cell proliferation
- photodynamic therapy
- oxidative stress
- high glucose
- drug release
- diabetic rats
- squamous cell
- solid state
- bone marrow
- childhood cancer
- endothelial cells