A GD2-aptamer-mediated Self-Assembling Nanomedicine for Targeted Multiple Treatments in Neuroblastoma Theranostics
2021
Abstract Since current mainstream anti-glycolipid GD2 therapeutics for neuroblastoma (NB) have limitations, such as severe adverse effects, improved therapeutics are needed. In this study, we developed a GD2 aptamer (DB99) and constructed a GD2-aptamer-mediated multifunctional nanomedicine (ANM) with effective, precise, and biocompatible properties that functioned both as chemotherapy and gene therapy for NB. DB99 can bind to GD2+ NB tumor cells but has minimal cross reactivity to GD2- cells. Furthermore, ANM is formulated by self-assembly of synthetic aptamers DB99 and NB-specific MYCN siRNA followed by self-loading of the chemotherapeutic agent Doxorubicin (Dox). ANM is capable of specifically recognizing, binding, and internalizing GD2+ NB tumor cells but not GD2- cells in vitro. Intracellular delivery of ANM activates Dox release for chemotherapy and MYCN siRNA-induced MYCN silencing. It is worth noting that ANM specifically targets and selectively accumulates in the GD2+ tumor site in vivo and further induces growth inhibition of GD2+ tumors in vivo; additionally, ANM generates fewer or no side effects in normal tissues, resulting in markedly longer survival with fewer adverse effects. These results suggest that the GD2 aptamer-mediated targeted drug delivery system may have potential applications for precise treatment of NB.
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