Engineered extracellular vesicles derived from sweet potato loaded with siPOLD1 for targeted therapy of glioma.

INTRODUCTION

Glioma is the most common malignant tumor of the central nervous system, with high malignancy and poor prognosis, necessitating the development of novel targeted therapies. DNA polymerase delta catalytic subunit 1 (POLD1) is implicated in multiple cancers, but its role in glioma remains unclear. Plant-derived extracellular vesicles (PDEVs) have emerged as biocompatible, targetable nanocarriers with promising applications in cancer therapy.

OBJECTIVE

This study aims to elucidate the oncogenic function of POLD1 in glioma and develop a PDEVs -based delivery system for targeted therapy, with the goal of improving the current therapeutic landscape for glioma.

METHODS

POLD1 expression and prognostic significance were analyzed using clinical samples and databases. In vitro, CCK-8, Transwell, and flow cytometry assays evaluated the impact of POLD1 knockdown on glioma cell proliferation, invasion, migration, cell cycle, and apoptosis. In vivo tumorigenesis and survival were assessed in mouse models. Sweet potato-derived nano-vesicles (SPDELNVs) were isolated and characterized. An engineered A2-SPDELNVs-siPOLD1 system was developed via surface modification and siRNA loading, and its targeting efficiency and therapeutic efficacy were evaluated both in vitro and in vivo.

RESULTS

POLD1 was upregulated in glioma tissues and correlated with poor prognosis. Its knockdown suppressed proliferation, invasion, and migration, induced cell cycle arrest, and promoted apoptosis in vitro. In vivo, POLD1 targeting inhibited tumor growth and prolonged survival. SPDELNVs showed intrinsic anti-glioma activity and efficient cellular uptake. The engineered A2-SPDELNVs-siPOLD1 effectively delivered siRNA, silenced POLD1, and significantly inhibited tumor progression both in vitro and in vivo, with enhanced survival.

CONCLUSION

Our findings uncover the oncogenic role of POLD1 in glioma and validate it as a promising therapeutic target. Furthermore, we establish a novel, plant-based A2-SPDELNVs-siPOLD1 delivery platform with effective BBB penetration and tumor targeting, offering a promising strategy for the treatment of glioma.