LAUSR

Tumorigenic environments, especially aberrantly over-expressed oncogenic microRNAs, play critical role in various activities of tumor progression. However, developing strategies to effectively utilize and manipulate these oncogenic microRNAs for tumor therapy is still a challenge. To address this challenge, we have fabricated spherical nucleic acids (SNAs) consisting of gold nanoparticles in the core and antisense oligonucleotides as the shell. Hybridized to the oligonucleotide shell was a DNA sequence to which doxorubicin was conjugated (DNA-DOX). The oligonucleotides shell was designed to capture over-expressed miR-21/miR-155 and inhibit the expression of these oncogenic miRNAs in tumor cells after tumor accumulation to manipulate genetic environment for accurate gene therapy. This process would further induce the aggregation of these SNAs, which not only generated photothermal agents to achieve on-demand photothermal therapy in situ, but enlarged the size of SNAs to enhance the retention time in tumor for sustained therapy. The capturing of the relevant miRNAs simultaneously triggered the intracellular release of the DNA-DOX from the SNAs to deliver tumor-specific chemotherapy. Both in vivo and in vitro results indicated that this combination strategy has excellent tumor inhibition properties with high survival rate of tumor-bearing mice, which could be a promising candidate for effective tumor treatment. This article is protected by copyright. All rights reserved.