Induction of apoptosis in human cancer cells by targeting mitochondria with gold nanoparticles

Abstract

A major challenge in designing cancer therapies is the induction of cancer cell apoptosis, although activation of intrinsic apoptotic pathways by targeting gold nanoparticles to mitochondria is promising. We report an in vitro procedure targeting mitochondria with conjugated gold nanoparticles and investigating effects on apoptosis induction in the human breast cancer cell line Jimt-1. Gold nanoparticles were conjugated to a variant of turbo green fluorescent protein (mitoTGFP) harbouring an amino-terminal mitochondrial localization signal. Au nanoparticle conjugates were further complexed with cationic maltotriose-modified poly(propylene imine) third generation dendrimers. Fluorescence and transmission electron microscopy revealed that Au nanoparticle conjugates were directed to mitochondria upon transfection, causing partial rupture of the outer mitochondrial membrane, triggering cell death. The ability to target Au nanoparticles into mitochondria of breast cancer cells and induce apoptosis reveals an alternative application of Au nanoparticles in photothermal therapy of cancer.

Engineered nanoparticles induce cell apoptosis: potential for cancer therapy

“…Mkandawire et al (2015) had AuNPs (20 nm) conjugated to a variant of turbo green fluorescent protein (mito TGFP) that harbored an amino-terminal mitochondrial localization signal. He then transfected the AuNPs conjugates into the human breast cancer cell line Jimt-1 [92]. The mitoTGFP-AuNPs conjugates were directed to mitochondria upon transfection, causing the rupture of the mitochondrial outer membrane, enabling the conjugates to make their way to the inner membrane.…”

Design, Fabrication and Characterization of Pressure-Responsive Films Based on The Orientation Dependence of Plasmonic Properties of Ag@Au Nanoplates

“…Research in noble metal nanoparticles with localized surface plasmon resonance (LSPR) properties has been around for a long time due to their broad applications in sensing 1–3 , catalysis 4–6 , therapeutics 7–9 , optical nanoantennas 10, 11 , and surface-enhanced Raman spectroscopy 12–15 . Their applications in the field of sensing focus on biosensors and chemical sensors based on the change of plasmonic properties related to refractive-index 1, 16, 17 , morphology 18, 19 , and assembly 3, 20–22 .…”

N‐Heterocyclic Carbene–Gold(I) Complexes Conjugated to a Leukemia‐Specific DNA Aptamer for Targeted Drug Delivery

“…A series of neutral and cationic NHC-Au complexes with a wide diversity of ligand structures were synthesized and characterized in recent years. [3–5] NHC-Au(I) complexes can induce cell apoptosis by targeting mitochondrial-related cellular pathways [6, 7] that involve thioredoxin reductase (TrxR) and Estrogen Receptor (ER). [3, 7] Though NHC-Au(I) complexes inhibit the growth of tumor cells, they also interact with human normal cells, a characteristic common for metal based drugs, [8] thus limiting their potential as cancer therapeutics.…”