iRGD-grafted N-trimethyl chitosan-coated protein nanotubes enhanced the anticancer efficacy of curcumin and melittin

Curcumin (Cur) and Melittin (Mel) are two natural extracts that have been shown anti-tumor effects. However, their applications are limited due to poor oral bioavailability and the lack of tumor-targeting property. Here, we developed a novel nanocomposite that enabled the co-delivery of Cur and Mel, which consists of α-lactalbumin protein nanotubes (NTs), positively charged N,N,N-trimethyl chitosan (TMC), and a tumor-targeting cyclic peptide iRGD. The results showed that NTs/Cur-TMC-Mel-iRGD incorporated the advantages of each component, for instance, effective compounds loading by NTs, improved cellular uptake by TMC, prolonged accumulation in tumors by iRGD as well as synergistic anti-tumor effects of Cur and Mel. In the tumor-bearing mice, NTs/Cur-TMC-Mel-iRGD treatment remarkably induced cancer cell apoptosis while inhibiting cell proliferation, leading to suppressed tumor growth. Besides, no obvious adverse effects were observed in the blood physiology and tissue histology. Overall, our study provided an effective strategy for co-delivering Cur and Mel, which has a potential for translational clinical research aiming to treat solid tumors.