Near-infrared PbS quantum dots functionalized with affibodies and ZnPP for targeted imaging and therapeutic applications

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