Tumorigenic environments, especially aberrantly overexpressed oncogenic
microRNAs, play a 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, spherical
nucleic acids (SNAs) consisting of
gold nanoparticles in the core and
antisense oligonucleotides as the shell are fabricated. Hybridized to the
oligonucleotide shell is
a DNA sequence to which
doxorubicin is conjugated (
DNA-DOX). The
oligonucleotides shell is designed to capture overexpressed 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 further induces the aggregation of these SNAs, which not only generates photothermal agents to achieve on-demand
photothermal therapy in situ, but also enlarges the size of SNAs to enhance the retention time in the
tumor for sustained
therapy. The capture of the relevant
miRNAs simultaneously triggers the intracellular release of the
DNA-DOX from the SNAs to deliver
tumor-specific
chemotherapy. Both in vivo and in vitro results indicate that this combination strategy has excellent
tumor inhibition properties with high survival rate of
tumor-bearing mice, and can thus be a promising candidate for effective
tumor treatment.