Inflammation Self-adaptive Nanocarriers For Highly Efficient Gene Therapy

Inflammation represents a real micromilieu of many diseases as well as the actual application environment of nanocarriers.However,few studies have focused on the influence of the inflammatory environment on the effects of nanoparticle delivery.Herein,a novel inflammation self-adaptive nanocarrier is designed and fabricated by attaching the ascorbyl palmitate(AP)onto the surface of gene-entrapped polymeric nanocomplexes through the formation of phenylboronate bond(PEI-PBA/DNA@AP).The negative surface formed by the self-assembly of AP on the surface of the polymeric nanocomplexes can provide an inflammation recognition target.After transporting to inflammatory site,the AP assembly can be destroyed by the up-regulation esterases in the inflammatory environment,and the surface charge of the nanoparticles can be changed from negative to positive,thus facilitating the cellular internalization of DNA payloads and consequently enhancing the gene therapy of inflammatory diseases.In vitro CLSM imaging and flow cytometry showed that the that the intracellular uptake of gene-loading nanoparticles is enhanced considerably.The fluorescence intensity in the Hela cells treated with PEI-PBA/DNA@AP under an inflammatory stimulus is 1.6-fold and 6.3-fold stronger than that in the cells treated with PEI-PBA/DNA under inflammation or normal environment,respectively.MTT analysis The cell viability of AP-free nanocomplexes was above 80% for the two cell lines whether it is in a normal or an inflammatory environment,while the cell viability of AP-present nanocomplexes was just around 30%.Meanwhile,the gene transfection efficiency of DNA and in vivo gene therapy of AP-present nanocomplexes under an inflammation stimulus is significantly enhanced about 1.3-fold.In addition,a more significant inhibition of the increase in paw thickness was observed in the rats treated with PEI-PBA/DNA@AP.Hence,our delicate design concept opens up a new pathway to develop an inflammation self-adaptive drug delivery system for precise drug/gene delivery and therapy.