Water-soluble PANI:PSS designed for spontaneous non-disruptive membrane penetration and direct intracellular photothermal damage on bacteria

The major challenge in the field of antibacterial agents is to overcome the low-permeability of bacteria cell membranes that protects the cells against diverse drugs.In this work,water-soluble polyaniline(PANI)-poly(p-styrenesulfonic acid)(PSS)(PANI:PSS)is found to spontaneously penetrate bacteria cellular membranes in a non-disruptive way,leaving no evidence of membrane poration/disturbance or cell death,thus avoiding side effects caused by cationic ammonia groups in traditional ammonia-containing antibacterial agents.For aqueous synthesis,which is important for biocompatibility,the polymer is synthesized via an enzyme-mimetic route relying on the catalysis of a nanozyme.Owing to its fluorescent properties,the localization of as-prepared PANI:PSS is determined by the confocal microscope,and the results confirm its rapid entry into bacteria.Under 808 nm near-infrared(NIR)irradiation,the internalized PANI:PSS generates local hyperthermia and destroys bacteria highly efficiently from inside the cells due to its excellent photothermal effects.Staphylococcus aureus(S.aureus),Methicillin-resistant Staphylococcus aureus(MRSA)and Escherichia coli(E.coli)could be effectively eliminated as well as the corresponding bacterial biofilms.Results of in vivo antibacterial experiments demonstrate excellent antibacterial activities of the water-soluble PANI:PSS without side effects.Therefore,the prepared water-soluble polymer in this study has great potential in the treatment of various bacterial infections.

Protein transduction domain of membrane penetrating peptide can efficiently deliver DNA and protein into mouse liver for gene therapy

BACKGROUND: The development of a harmless and effi- cient nonviral gene delivery system that can facilitate the penetration of nucleic acids through the plasma membrane is a key to successful gene therapy. The aim of this study was to test a nonviral gene transferring vector's function of delivering DNA into liver cells to provide an important clue for gene transfer in liver gene therapy. METHODS: The complex of DNA and DNA delivering protein was injected into mice through their tail veins. Then the mice were killed and their liver tissue was sec- tioned. The gene transferring results were detected using a confocal laser scanning microscope. RESULTS: Fluorescence analysis indicated that both DNA- membrane penetrating peptide (MPP) complex and DNA- hepatocyte specific receptor binding domain ( HSRBD) - MPP complex could go into liver cells. The fluorescence value of liver cells in the DNA-HSRBD-MPP group was higher than that in the DNA-MPP group. CONCLUSIONS; MPP can successfully deliver DNA and protein into cells, and MPP with a HSRBD can specifically deliver DNA into liver cells. These have laid a foundation for further study on the nonviral liver cell gene delivering system.

Hepatocyte gene transfer mediated by stable polyplexes based on MPP-containing DNA complexes

BACKGROUND: In the field of gene therapy, viral vectors as delivery tools have a number of disadvantages for medical application. This study aimed to explore a novel nonviral vector as a vehicle for gene therapy. METHODS: Transvector-rpE-MPP and EGFP (enhanced green fluorescent protein) were used as the gene transfer carrier and the reporter gene, respectively. Polyplexes which integrate transvector-rpE-MPP, the object gene, and EGFP were formed. The optimal charge ratio, stability, and transduction capacity of the polyplexes in mouse hepatocytes in vitro and in mouse liver in vivo were investigated. The polyplexes of transvector-rpE-MPP and pcDNA(3)-EGFP, with charge ratios of 0, 0.25, 0.5, 0.75, 1 and 1.5 were compared to determine the optimal charge ratio. RESULTS: Polyplexes with charge ratios of 1: 1 were most stable; pcDNA(3)-EGFP in these complexes resisted digestion by DNase I and blood plasma. On the other hand, pcDNA(3)-EGFP alone was digested. Fluorescence analysis indicated that transvector-rpE-MPP successfully delivered the reporter gene EGFP into hepatocytes and that EGFP expression was detected in hepatocyte cultures and in liver tissue. CONCLUSION: These results have laid a foundation for further study of a novel nonviral gene delivery system.