A GD2-aptamer-mediated, self-assembling nanomedicine for targeted multiple treatments in neuroblastoma theranostics
Because 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 effec...
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Veröffentlicht in: | Molecular therapy. Nucleic acids 2021-12, Vol.26, p.732-748 |
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Sprache: | eng |
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Zusammenfassung: | Because 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, which functioned both as chemotherapy and as 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 small interfering RNA (siRNA), followed by self-loading of the chemotherapeutic agent doxorubicin (Dox). ANM is capable of specifically recognizing, binding, and internalizing GD2+, but not GD2−, NB tumor cells in vitro. Intracellular delivery of ANM activates Dox release for chemotherapy and MYCN-siRNA-induced MYCN silencing. ANM specifically targets, and selectively accumulates in, the GD2+ tumor site in vivo and further induces growth inhibition of GD2+ tumors in vivo; in addition, ANM generates fewer or no side effects in healthy 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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Multifunctional nanomedicine (ANM), with effective, precise, and biocompatible properties based on a GD2 aptamer, to achieve both chemotherapy and gene therapy of neuroblastoma was constructed by Zhang et al. This GD2-aptamer-mediated, targeted, multifunctional nanomedicine system may open a new avenue and have potential applications for precision treatment of NB. |
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ISSN: | 2162-2531 2162-2531 |
DOI: | 10.1016/j.omtn.2021.08.021 |