Engineering Laboratory of Animal Immunity of Jiangsu Province, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, P.R. China.
College of Biology and Food Science, Shangqiu Normal University, Shangqiu, Henan, 476000, P.R. China.
Sci Rep. 2017 Sep 11;7(1):11242. doi: 10.1038/s41598-017-11687-y.
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.
在这项研究中，我们设计了一种纳米系统，将新型抗菌肽 RGD-hylin a1 负载到介孔硅（HMS）上，该抗菌肽的溶血作用比常用的蜂毒素低。我们发现，设计的纳米系统 RGD-hylin a1-HMS 以 pH 依赖性方式释放 RGD-hylin a1。在 pH = 5.5 时，低剂量的抗菌肽即可诱导癌细胞凋亡，但在 pH = 7 时对细胞是安全的。纳米系统可将 RGD-hylin a1 本身的溶血活性降低 50%100%，具体取决于剂量。当该纳米系统以低剂量通过静脉注射给药给荷瘤小鼠时，与 PBS 处理的对照组相比，RGD-hylin a1-HMS 纳米系统使实体瘤的生长受到抑制，肿瘤体积和重量的抑制率为 50%60%。此外，在递送系统内，RGD-hylin a1 的溶血活性完全消除，没有观察到其他副作用。这项研究表明，这种智能 pH 依赖性抗菌肽释放纳米系统通过静脉给药具有治疗实体瘤的巨大潜力。这种智能释放系统在进一步的临床应用中具有巨大的潜力。
