Capturing and deactivation of circulating tumor cells using lipid nanoparticles with decreased systemic clearance

Circulating tumor cells (CTCs) are cancer cells with metastatic characteristics, enabling their distant translocation from the primary tumor site. However, limited number of CTCs in the blood has made their diagnosis and treatment extremely challenging. In this study, we designed anti-phagocytosis peptide PepCD47-and CTC recognition peptide Pep10-modified solid lipid nanoparticles (SLNs) with docetaxel (DTX) encapsulation. Various nanoparticles including SLNs, SLNs-PEG6000, SLNs-PepCD47, SLNs-Pep10, and SLNs-PepCD47-Pep10 were prepared using an emulsion–solvent evaporation method. The cellular uptake of SLNs-PepCD47 in RAW264.7 macrophages was extremely low compared with that of SLNs-PEG6000. The modification of Pep10 resulted in the specific uptake of SLNs in MCF-7 but not in other cell types. In addition, SLNs-PepCD47-Pep10 was also found to specifically target MCF-7 cells in vivo. DTX encapsulation in SLNs-PepCD47-Pep10 induced excellent CTC killing effects compared with the DTX-SLN group. The repeated dose of SLNs-PepCD47-Pep10 showed a relatively reduced accelerated blood clearance phenomenon compared to SLNs-PEG6000. In conclusion, our dual peptide-modified SLNs provide an alternative strategy for improving the ability to capture CTCs and reducing systemic clearance.