Antimicrobial peptide modification enhances the gene delivery and bactericidal efficiency of gold nanoparticles for accelerating diabetic wound healing

Abstract

Impaired angiogenesis and bacterial infection have increasingly been implicated as the major causes of delayed diabetic wound healing. However, there is currently no effective therapy. Here, we optimized a novel gene delivery system based on antimicrobial peptide (LL37) grafted ultra-small gold nanoparticles (AuNPs@LL37, ∼7 nm) for the topical treatment of diabetic wounds with or without bacterial infection. AuNPs@LL37 combines the advantages of cationic AuNPs that condense DNA with those of antibacterial peptides, which are both highly antibacterial and essential for enhancing cellular and nucleus entry to achieve high gene delivery efficiency. AuNPs@LL37 combined with pro-angiogenic (VEGF) plasmids (AuNPs@LL37/pDNAs) significantly improved the gene transfection efficiency in keratinocytes compared with pristine AuNPs/pDNAs, and showed similar expression to Lipo2000/pDNAs (a well-known highly efficient gene transfection agent). Moreover, our therapeutic depot showed higher antibacterial ability than the free antimicrobial peptides and the cationic AuNPs alone in vitro and in vivo due to synergistic effects. Furthermore, the combined system promoted angiogenesis and inhibited bacterial infection in diabetic wounds, resulting in accelerated wound closure rates, faster re-epithelization, improved granulation tissue formation and high VEGF expression. Finally, our therapeutic depot was highly biocompatible in vitro and in vivo, suggesting its potential as a feasible way to treat chronic diabetic wounds.

Outer membrane protein A (OmpA) as a potential therapeutic target for Acinetobacter baumannii infection

“…In vivo, the intraperitoneal injection of AOA-2 (10 mg/kg) in combination with CST (10 mg/kg) improved the survival rate of mice with bacteraemia by 20% [72,73]. In addition, some classic antimicrobial peptides (AMPs) interacting with AbOmpA have been gradually discovered, which are a series of endogenous defense peptides to kill bacteria and fungus [74][75][76]. For example, bovine myeloid antimicrobial peptide (BMAP-28) and its analog peptides killed MDR-A.…”

Insights into the angiogenic effects of nanomaterials: mechanisms involved and potential applications

“…In vitro study [17] Micro-nano bioactive glass particles In vitro study [31] Mesoporous silica nanoparticles In vitro study [32] Soft tissue wound healing Gold nanoparticles (1) In vitro study (2) In vivo wound model [14,38,43,44] Nano-sized bioactive glass (1) In vitro study (2) In vivo wound healing assay [39] Cerium oxide nanoparticle (1) In vitro study (2) In vivo wound model [42] the PCL nano-composite membranes incorporated with Zn-doped hollow mesoporous silica nanospheres…”

“…On one hand, stress is supported by embedded nanofibres, so that the elasticity of matrix is reinforced. On the other hand, they have been demonstrated to improve the adhesion and proliferation of endothelial cells and promote angiogenesis [35][36][37][38].…”

“…Functional peptide-coated gold nanoparticles promote endothelial cell capillary formation based on the proangiogenic function of peptides [38,61,62]. Carbon nanoparticle-grafted functional groups containing oxygen and nitrogen (e.g., amines and amide groups) reverse the negative zeta potential of unmodified carbon nanotubes, and chitosan-mediated cation electrodepositioncoated nanoparticles interact better with the negatively charged cell membrane, thereby increasing the adhesion, activity and proliferation of HUVECs and vascular smooth muscle cells [63,64].…”

Evaluation of the potential of nanoparticles containing active substances in selected chronic diseases

“…Previous studies have shown the ability of Au NPs, based on antimicrobial peptide combined with pro-angiogenic (vascular endothelial growth factor (VEGF)) plasmids, to promote angiogenesis and inhibit bacterial infection in diabetic wounds, resulting in faster re-epithelization, improved granulation tissue formation and high VEGF expression. 103 Curcumin NPs were found to have strong antibacterial activity to suppress the growth of Pseudomonas aeruginosa and Staphylococcus aureus. 104 It was also demonstrated that curcumin NPs could reduce inflammation and induce cell expansion, which is useful in the reconstruction of damaged tissue.…”