Abstract
We report a new theranostic device based on lead sulfide quantum dots (PbS QDs) with optical emission in the near infrared wavelength range decorated with affibodies (small 6.5 kDa protein-based antibody replacements) specific to the cancer biomarker human epidermal growth factor receptor 2 (HER2), and zinc(II) protoporphyrin IX (ZnPP) to combine imaging, targeting and therapy within one nanostructure. Colloidal PbS QDs were synthesized in aqueous solution with a nanocrystal diameter of ∼5 nm and photoluminescence emission in the near infrared wavelength range. The ZHER2:432 affibody, mutated through the introduction of two cysteine residues at the C-terminus (Afb2C), was used as capping ligand to form Afb2C-PbS QDs that have a high binding affinity for HER2, which is overexpressed in several types of cancer including breast cancer. Afb2C-PbS QDs were further modified by conjugation with ZnPP, which acts as an anticancer agent. The biological activity of these QDs was tested against SKBR3 (HER2-positive) and MDA-MB-231 (HER2-normal) breast cancer cells, with results showing that ZnPP-Afb2C-functionalized PbS QDs were successfully targeted to the HER2-overexpressing cancer cells and induced cell apoptosis thanks to the conjugation with ZnPP. These results expand the use of the QD nanoplatform with the formulation of novel nanomaterials for targeted delivery and combined imaging and therapy via direct surface-protein interaction.
Highlights
The development of theranostic agents for simultaneous disease detection and targeted therapy has attracted considerable attention in recent years and brought significant advances to cancer treatments [1, 2]
In the pJexpress401 plasmid, the Afb2C gene was designed with an N-terminal His-tag, and two mutations (G82C and S83C) which were introduced at its C-terminus; we note that these residues were not critical for the Afb binding to HER2 (Supplementary Information, SI1)
The mutant Afb2C protein was successfully expressed in BL21 (DE3) E. coli and purified using nickel(II)-immobilized metal affinity chromatography (IMAC) followed by further purification by size exclusion chromatography (SEC)
Summary
Commons Attribution 4.0 Keywords: affibody, PbS QDs, zinc(II) protoporphyrin IX, HER2, breast cancer, quantum dots licence. The biological activity of these QDs was tested against SKBR3 (HER2-positive) and MDA-MB-231 (HER2-normal) breast cancer cells, with results showing that ZnPP-Afb2C-functionalized PbS QDs were successfully targeted to the HER2-overexpressing cancer cells and induced cell apoptosis thanks to the conjugation with ZnPP. These results expand the use of the QD nanoplatform with the formulation of novel nanomaterials for targeted delivery and combined imaging and therapy via direct surface-protein interaction
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
