A GD2-aptamer-mediated, self-assembling nanomedicine for targeted multiple treatments in neuroblastoma theranostics

Liyu Zhang; Meng Wang; Zeen Zhu; Shengquan Chen; Haibin Wu; Ying Yang; Fengyu Che; Qiao Li; Hui Li

Molecular Therapy: Nucleic Acids (Dec 2021)

A GD2-aptamer-mediated, self-assembling nanomedicine for targeted multiple treatments in neuroblastoma theranostics

Liyu Zhang,
Meng Wang,
Zeen Zhu,
Shengquan Chen,
Haibin Wu,
Ying Yang,
Fengyu Che,
Qiao Li,
Hui Li

Affiliations

Liyu Zhang: Department of Neonatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China; Shaanxi Institute of Pediatric Diseases, Affiliated Children’s hospital of Xi’an Jiaotong University, Xi’an 710002, Shaanixi, China
Meng Wang: Department of Emergency Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi, China
Zeen Zhu: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
Shengquan Chen: Department of Neonatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
Haibin Wu: Shaanxi Institute of Pediatric Diseases, Affiliated Children’s hospital of Xi’an Jiaotong University, Xi’an 710002, Shaanixi, China
Ying Yang: Shaanxi Institute of Pediatric Diseases, Affiliated Children’s hospital of Xi’an Jiaotong University, Xi’an 710002, Shaanixi, China
Fengyu Che: Shaanxi Institute of Pediatric Diseases, Affiliated Children’s hospital of Xi’an Jiaotong University, Xi’an 710002, Shaanixi, China
Qiao Li: Department of clinical laboratory, Affiliated Children’s hospital of Xi’an Jiaotong University, Xi’an 710002, China
Hui Li: Department of Neonatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China; Department of Neonatology, Affiliated Children’s hospital of Xi’an Jiaotong University, Xi’an 710002, China; Corresponding author: Hui Li, Department of Neonatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China.

Journal volume & issue: Vol. 26
pp. 732 – 748

Abstract

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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.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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