γ-Cyclodextrin–folate complex-functionalized quantum dots for tumor-targeting and site-specific labeling

Abstract

Quantum dots (QDs) encapsulated with high affinity ligands, specifically binding organic ligands, such as antibodies, peptides or small molecules, have been used in intracellular imaging and targeting. In this work, a series of folate-receptor targeted QDs, in which tumor-targeting folic acid (FA) was conjugated to the surface of QDs through cell-penetrated γ-cyclodextrin (γ-CD), was synthesized. The QDs showed good optical properties and biocompatibility, such as strong optical emission, long luminescent lifetime, appropriate size (4–5 nm in diameter), and lower toxicity. In particular, the γ-CD–FA-coated CdSe–ZnSe QDs presented lower cytotoxicity to these cells at higher IC₅₀ concentrations of above 200 μg mL⁻¹ for 48 h. Folate-receptor overexpressed FR(+) and folate-receptor deficient FR(−) cells were incubated with folate-receptor targeted γ-CD–FA-coated QDs and non-targeted L-Cys-β-CD-coated QDs in vitro. It was found that folate-receptor targeted QDs could more effectively recognize cancer cells with folate receptor (FR) over-expression compared to non-targeted QDs by flow cytometry and confocal laser scanning microscopy (CLSM). Confirming the specificity of folate-receptor targeted QDs, binding and internalization were inhibited by free folate, and hardly any uptake was found in FR(+) cells. Inside the cells, the γ-CD–FA-functionalized QDs are mostly distributed within lysosomes. These properties not only offer insights into the mechanism of the functionalized QDs delivery but also will guide the design and development of nanoparticle probes for intracellular imaging and targeting applications.