MicroRNAs (
miRNAs) play crucial roles in maintaining normal physiological processes by regulating gene expression network and thus the
tumor-suppressive
miRNA has emerged as a promising
antitumor agent for
cancer treatment. However, targeted delivery of
miRNA remains a challenge owing to its intrinsic macromolecular and negatively-charged features. Herein, we first employ the
miRNA as crosslinker to construct a
nucleic acid nanogel, in which
miRNA is embedded and protected inside the three-dimensional (3D) nanostructure. Thereafter, nanobody (Nb) conjugated
DNA (Nb-
DNA) strands are further loaded on
nanogel surface through nucleic acid hybridization, to form a Nb-functionalized
nanogel (Nb-
nanogel) for
tumor-targeted
miRNA delivery and antitumor treatment. Both in vitro and in vivo experiments show that
nanogel equipped with Nb targeting moieties can greatly promote the
miRNA accumulation at the
tumor site and cellular uptake efficiency, resulting in significant improvement of the
miRNA-mediated antitumor efficacy. This research provides a new approach for targeted
miRNA delivery and may pave a new avenue to realize efficient
miRNA replacement
therapy for
cancer treatment.