Unidirectional gene delivery electrospun fibrous membrane via charge repulsion for tendon repair

Abstract

Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases. However, unidirectional targeting gene therapy is always desired at the tissue interface. In this study, inspired by the principle that like charges repulse each other, a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers, thus realizing unidirectional gene therapy at the tendon-paratenon interface. Under the charge repulsion of positively charged layer, more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue, which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation, but also avoided adverse effects on the fragile endogenous healing of tendon itself. In summary, this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.