Characterization of high-affinity peptides and their feasibility for use in nanotherapeutics targeting leukemia stem cells

Peptides featuring the LR(S/T) motif were identified that could specifically bind to the C-type lectin-like molecule-1 (CLL1), a protein preferentially expressed on acute myeloid leukemia stem cells (LSCs). Micellar nanoparticles were covalently decorated with CLL1-targeting peptides for targeted drug delivery. The resulting peptide-coated nanoparticles were 13.5 nm in diameter and could be loaded with 5 mg of daunorubicin per 20 mg of telodendrimers. These “targeting nanomicelles” transported the drug load to the interior of cells expressing CLL1 and to LSCs isolated from clinical specimens in vitro, but did not bind to normal blood or normal hematopoietic stem cells. The presence of CLL1-targeting peptides on the surface of the nanomicelles enabled the improved binding and delivery of substantially more daunorubicin into the cells expressing CLL1 and CD34+ leukemic cells compared with unmodified nanomicelles. In conclusion, nanomicelles coated with CLL1-targeting peptides are potentially useful for eradicating LSCs and improving leukemia therapy.From the Clinical EditorMicellar nanoparticles covalently decorated with targeting peptides were used for targeted drug delivery of daunorubicin to address acute myeloid leukemia stem cells.

Graphical AbstractA chemotherapeutic drug, drug combinations and/or radioisotopes are loaded inside nanomicelles. Targeting ligands against leukemia stem cell (LSC) surface molecules are decorated on the surface of nanomicelles. After intravenous administration, these targeting nanomicelles can specifically deliver high-concentration therapeutic agents to and eradicate LSC. In addition, the therapeutic agents can diffuse into blood circulation to kill leukemic cells throughout the body. Furthermore, formulation of chemotherapeutic drugs in nanomicelles can decrease therapy-related toxicity and improve treatment outcomes.Figure optionsDownload high-quality image (333 K)Download as PowerPoint slide