Peptide Drones Facilitating the Transdermal Delivery of Antitumor Proteins for Melanoma Treatment

Abstract Topical treatment offers a viable alternative for melanoma patients incompatible with surgical interventions. Herein, the study develops a skin‐penetrating peptide (SPP)‐based peptide drone (PD) for the transdermal delivery of antitumor proteins. To achieve cost‐effective therapeutics, Concanavalin A (ConA), which can be prepared through an extraction method, is loaded onto PDs. Compared with free proteins, ConA‐PD complexes (CPCs) demonstrate significantly greater skin permeation. Moreover, the CPCs exhibit potent anticancer activity both in vitro and in vivo, which substantially surpass the efficacy of the Aldara (imiquimod) cream. The CPC‐treated mouse skin remains clear, whereas Aldara cream induces side effects, including psoriasis‐like skin inflammation. The antimetastatic activity of the PD is identified as another advantage of CPC. The use of ConA as an anticancer agent has been significantly limited due to its high hepatotoxicity; however, the transdermal delivery strategy minimizes its hepatic absorption and, in turn, results in negligible hepatotoxicity. These results demonstrate the potential of the CPC as a novel therapeutic agent or an adjunct to other modalities for melanoma treatment, overcoming the limitations of existing materials while exhibiting superior efficacy.