Targeted Delivery Of MiR155 Antisense By Functionalized Mesoporous Silica Nanoparticles For Colorectal Cancer Therapy

Micro RNAs(miRNAs)constitute an attractive candidate for treatment of a myriad of important human diseases including cancer.However,the effective systemic in vivo delivery of mi RNA to tumors remains challenging.The mi R155 is dysregulated in many cancers and might serve as a novel therapeutic target for patients with CRC.Herein,we evaluate the miR155 expression level in CRC tissues and report a anti-miR155-loaded mesoporous silica nanoparticle(MSN)coated with polydopamine(PDA)and AS1411 aptamer(MSNs-anti-mi R155@PDA-Apt)for the targeted treatment of colorectal cancer.In this system,the PDA can work as p H-sensitive gatekeepers to control the release of anti-miR155 from MSNs in response to the pH-stimulus and PEG was further grafted on the surface of PDA to to increase the local effective drug concentration on tumor sites.Results showed that miR155 is overexpression in CRC tissues and significantly correlated with poor prognosis.MSNs-anti-miR155@PDA-Apt could efficiently downregulate miR155 expression in SW480 cells and achieve significantly high targeting efficiency and enhanced therapeutic effects than free anti-miR155 and NPs without functional modification both in vivo and in vitro experiments.Further,inhibition of mi R155 by MSNs-anti-miR155@PDA-Apt can the sensitivity of SW480 to 5-FUchemotherapy.Thus,our results suggested that MSNs-anti-miR155@PDA-Apt is a promising nanoformulation for colorectal cancer treatment.