Oral solid lipid nanoparticles of etoposide enable metronomic-like therapy with reduced toxicity in MYCN-amplified neuroblastoma

Therapeutic regimens for pediatric malignancies such as neuroblastoma remain complex and are often associated with severe systemic toxicity. The development of more efficacious and less toxic therapeutic strategies is imperative to enhance both overall survival and the quality of life for high-risk patients. Cancer nanomedicine has emerged as a transformative platform in oncology, enabling precision therapies and targeted delivery of chemotherapeutic agents. In this study, we designed solid lipid nanoparticles encapsulating the topoisomerase II inhibitor etoposide, aiming to reformulate this agent for oral administration in the treatment of aggressive neuroblastoma. Nanoencapsulation significantly improved the pharmacokinetic and biodistribution profiles of the drug, enhancing its bioavailability and tumor accumulation. To simulate a metronomic dosing regimen, MYCN-amplified SK-N-BE(2) tumor-bearing mice received up to ten oral administrations over a 30-day period. The nanoformulation demonstrated superior antitumor efficacy and a markedly reduced toxicity profile compared to both oral and intravenous commercial formulations. These findings support the potential of nanomedicine-based strategies as safer and more effective alternatives to conventional chemotherapy in neuroblastoma. • Nanoencapsulation enhances the therapeutic perspectives of etoposide. • Solid lipid nanoparticles loaded with etoposide exhibited high antitumor efficacy in MYCN-amplified neuroblastoma. • Orally administered cancer nanomedicines create new opportunities in the field of metronomic-like therapies.