WOFAPS 2025 8th World Congress of Pediatric Surgery

Yutian Li

Dalian Women and Children's Medical Group,Department of Pediatric Surgery,Dalian,China

Purpose:

Neuroblastoma (NB), a malignancy arising from sympathetic neural crest precursors, is among the most common solid tumors in children. Its rapid progression and poor prognosis—especially in advanced cases—are exacerbated by drug resistance to conventional chemotherapy. Hypoxia-inducible factor-1α (HIF-1α), a key regulator of tumor adaptation to hypoxic environments, is highly expressed in the NB microenvironment and contributes to tumor progression, invasion, and metastasis. This study aimed to develop and evaluate a dual-drug nanoliposome system co-encapsulating the HIF-1α inhibitor 17-AAG and the chemotherapeutic agent doxorubicin (Dox) for enhanced anti-tumor efficacy against NB.

Methods:

Single (Lip-Dox, Lip-17-AAG) and dual-loaded (Lip-17-AAG-Dox) nanoliposomes were prepared using the thin-film hydration method. Particle size and morphology were assessed by dynamic light scattering and transmission electron microscopy. Stability was evaluated in phosphate-buffered saline and serum-containing media over seven days. In vitro studies employed murine (N2a) and human (SH-SY5Y) neuroblastoma cell lines to assess cellular uptake, cytotoxicity (MTT assay), and apoptosis induction. An in vivo mouse model of neuroblastoma was established for therapeutic evaluation.

Results:

Dual-loaded nanoliposomes displayed uniform morphology, favorable size distribution, and good stability. Cellular uptake studies confirmed efficient internalization by NB cells. Compared with single-drug formulations, Lip-17-AAG-Dox significantly enhanced cytotoxicity and apoptosis rates in vitro. In vivo, the dual-loaded nanoliposomes demonstrated superior tumor growth inhibition and downregulation of HIF-1α expression.

Conclusion:

The co-delivery of 17-AAG and Dox via nanoliposomes offers a promising therapeutic strategy for neuroblastoma by simultaneously targeting hypoxia response pathways and inducing cytotoxic effects. This dual-drug nanoformulation has potential to overcome drug resistance and improve clinical outcomes in NB treatment.