Fibrin-targeting peptide CREKA-conjugated multi-walled carbon nanotubes for self-amplified photothermal therapy of tumor

Abstract

Inability of nanomedicine to efficiently home to tumor site still poses great challenge in tumor drug delivery. Inspired by the amplified formation of fibrin in clotting cascade, a self-amplified drug delivery system was developed for tumor photothermal therapy (CMWNTs-PEG) using multi-walled carbon nanotubes (MWNTs) with favorable photothermal effect as the vector, polyethylene glycol as the shelter, CREKA peptide with special affinity for fibrin as the targeting moiety and NIR illumination as the external power. The self-amplified targeting property was carefully characterized. The in vivo temperature monitoring experiment demonstrated that CMWNTs-PEG could significantly elevate the temperature in the tumor region than its counterpart 24 h post an initial NIR illumination. The in vivo imaging and biodistribution experiment showed IR783-labeled CMWNTs-PEG with illumination could accumulate in tumors tissues about 6.4-fold higher than control group, much stronger than other treatment groups. In vivo distribution experiments revealed Cy3-labeled CMWNTs-PEG could deposit on the wall of tumor vessels, intravascular and extravascular spaces, far more extensive than its counterpart in tumor slices. The pharmacodynamics experiment revealed that after four times of illumination, the CMWNTs-PEG almost totally eradiated the tumor xenografts. Altogether, the self-amplified targeting system CMWNTs-PEG showed strong tumor targeting capacity and powerful photothermal therapeutic efficacy.

Keywords: CREKA; Fibrin-targeting peptide; Multi-walled carbon nanotubes; Photothermal therapy; Self-amplified.