| Acute lung injury (ALI) is a major cause of mortality after lung transplantation. Recent studies indicate protein kinase C delta (PKCdelta) could be an effective target to treat ALI. We have developed a gold nanoparticle (GNP)-peptide hybrid that can inhibit PKCdelta signaling. PKCdelta inhibitor peptide (PKCi) and 95P2P4 stabilizing peptides were conjugated onto GNP. Physicochemical properties of the nanoformulations were examined. A lung transplant-simulated cell culture model was used to evaluate therapeutic efficacy in vitro. A pulmonary ischemia-reperfusion (IR) model was used to test therapeutic efficacy in vivo. GNP-Peptide hybrids showed good stability with high cellular uptake. GNP-PKCi formulations demonstrated anti-inflammatory and anti-apoptotic effects in vitro. When administered to rats under IR stress, GNP-PKCi formulation improved blood oxygenation, reduced pulmonary edema and histological lung injury. In conclusion, we have successfully formulated a clinically-applicable nanoparticle with therapeutic potential to ameliorate lung injury and inflammation. Our formulation strategy could be used to deliver other peptide-based drugs. |
