Incorporating more than one ligand with nanoparticle-based carriers for specific delivery of therapeutic nucleic acids – such as antisense oligonucleotides (AS-ODNs) and siRNA – to tumour sites is a promising approach in anti-cancer strategies. However, as they possess a negative charge they cannot permeate across biological membranes freely.

Visibility and tracking

As an alternative, quantum dots (QDs) can be used as gene carriers in tumour gene regulation. They provide an entirely visible means to investigate gene intracellular transport and the targeted uptake of nucleic acids. In this gene-delivery system, QDs can not only be used as a gene vehicle but also as a fluorescent probe, allowing for localization and tracking during the delivery process.

The gene carrier

Here, biotinylated peptide GE11, c(RGDfK) and AS-ODN are conjugated with QDs by the interaction of streptavidin (SA) and biotin. This forms their gene carrier: QD-(AS-ODN+GE11+c(RGDfK)). The absorbance and fluorescence spectra, capillary electrophoresis, agarose electrophoresis and transmission electron microscopy (TEM) are used to characterize the conjugation.

Efficient transfection

The researchers demonstrate the synergistic effect between epidermal growth factor receptors (EGFR) and integrin ανβ3 by quantitative flow cytometry and inductively coupled plasma mass spectrometry (ICP/MS). They then confirm that the endocytosis pathway of the QD-(AS-ODN+GE11+c(RGDfK)) probe is mainly mediated by clathrin using special endocytosis inhibitors. Western blot further confirms that QD-(AS-ODN+GE11+c(RGDfK)) can enhance gene silencing efficiency compared with QD-(AS-ODN+GE11) and QD-(AS-ODN +c(RGDfK)). This suggests that this dual receptor targeted gene carrier achieves the desired transfection efficiency for its application.

More information can be found in the journal Nanotechnology 25 255102.

Further reading

'Living' PEGylation could improve cancer therapy (Sept 2013)
Aptamer and peptide functionalized quantum dots recognize tumour cells (Nov 2012)