No abstract

Biofilms formed by pathogenic bacteria are one of the most important reasons for multidrug resistance.

No abstract

No abstract

Antithrombosis therapy is confronted with short half-lives of thrombolytic agents, limited therapeutic effects, and bleeding complications. Drug delivery systems of thrombolytic agents face challenges in effective penetration into thrombi, which are characterized by well-organized fibrin filled with abundant activated platelets. Herein, Janus rod (JR)-shaped micromotors are constructed by side-by-side electrospinning and cryosection, possessing advantages in controlling the Janus structure and aspect ratio of microrods. Silicon phthalocyanine (Pc) and CaO2 nanoparticles (NPs) are loaded into the separate sides of JRs, and Arg-Gly-Asp (RGD) peptides are grafted on the surface to obtain Pc/Ca@r-JRs for the sonodynamic therapy (SDT) of thrombosis without using any thrombolytic agents. Decomposition of CaO2 NPs ejects O2 bubbles from one side of JRs, and ultrasonication of O2 bubbles produces the cavitation effect, both generating mechanical force to drive the thrombus penetration. The integration of ultrasonication-propelled motion and RGD mediation effectively increases the targeting capabilities of r-JRs to activated platelets. In addition to mechanical thrombolysis, ultrasonication of the released Pc produces 1O2 to destruct fibrin networks of clots. In vitro thrombolysis of whole blood clots shows that ultrasonication of Pc/Ca@r-JRs has a significantly higher thrombolysis rate (73.6%) than those without propelled motion or RGD-mediated clot targeting. In a lower limb thrombosis model, intravenous administration of Pc/Ca@r-JRs indicates 3.4-fold higher accumulations at the clot site than those of JRs, and ultrasonication-propelled motion further increases thrombus retention 2.1 times. Treatment with Pc/Ca@r-JRs and ultrasonication fully removes thrombi and significantly prolongs tail bleeding time. Thus, this study has achieved precise and prompt thrombolysis through selective targeting to clots, efficient penetration into dense networks of thrombi, and SDT-executed thrombolysis.

No abstract

The efficient delivery of nucleic acids as therapeutic agents is a major challenge in gene therapy. Peptides have recently emerged as a novel carrier for delivery of drugs and genes. C6M1 is a designed amphipathic peptide with the ability to form stable complexes with short interfering RNA (siRNA). The peptide showed a combination of random coil and helical structure in water but mainly adopted a helical conformation in the presence of anions or siRNA. Revealed by dynamic light scattering (DLS) and microscopy techniques, the interaction of C6M1 and siRNA in water and HEPES led to complexes of ∼70 and ∼155 nm in size, respectively, but showed aggregates as large as ∼500 nm in PBS. The time-dependent aggregation of the complex in PBS was studied by DLS and fluorescence spectroscopy. At molar ratio of 15∶1, C6M1 was able to completely encapsulate siRNA; however, higher molar ratios were required to obtain stable complexes. Naked siRNA was completely degraded in 4 h in the solution of 50% serum; however C6M1 protected siRNA against serum RNase over the period of 24 h. Western blotting experiment showed ∼72% decrease in GAPDH protein level of the cells treated with C6M1-siRNA complexes while no significant knockdown was observed for the cells treated with naked siRNA.

Biofilm infection is regarded as a major contributing factor to the failure of burn treatment and the persistent inflammatory state destines healing delays and the formation of chronic wounds. Herein,...