A pH-dependent Antibacterial Peptide Release Nano-system Blocks Tumor Growth in vivo without Toxicity.

In this study, we designed a nano-system where a novel antibacterial peptide RGD-hylin a1 with reduced hemolysis than the commonly studied melittin was loaded onto mesoporous silica (HMS). We found out that the designed nano-system, RGD-hylin a1-HMS, released RGD-hylin a1 in a pH-dependent manner. It caused apoptosis of cancer cells at low dosage of the antibacterial peptide at pH = 5.5, but was safe to the cells at pH = 7. The hemolytic activity of RGD-hylin a1 itself was reduced by 50~100% by the nano-system depending on the dosage. When this nano-system was administered to tumor-bearing mice at low dosage via intravenous injection, the growth of the solid tumor was blocked by the RGD-hylin a1-HMS nano-system with a 50-60% inhibition rate relative to the PBS-treated control group in terms of tumor volume and weight. Further, the hemolytic activity of RGD-hylin a1 was completely eliminated within the delivery system with no other side effects observed. This study demonstrates that this smart pH-dependent antibacterial peptide release nano-system has superior potential for solid tumor treatments through intravenous administration. This smart-releasing system has great potential in further clinical applications.