2ⁿᵈ Edition of the Cancer R&D World Conference 2026

Abstract

Lipid nanoparticles (LNPs) represent an established non-viral platform for RNA delivery, yet their therapeutic use in oncology is still constrained by suboptimal tumor targeting. Cancer cell membranes display distinctive surface markers that can be exploited to improve the selective interaction of nanocarriers with tumor cells and stromal components.

In this work, we developed a biomimetic core–shell nanoplatform in which RNA-loaded LNPs are enveloped within cancer cell membrane-derived nano-ghosts (CCM-NGs), designed to reproduce the molecular identity of tumor cell surfaces.

CCM-NGs were fluorescently labelled and characterized for their physicochemical and membrane-associated features. RNA-loaded LNPs were generated through microfluidic mixing and subsequently incorporated into CCM-NGs to form hybrid biomimetic nanoparticles. Their targeting capability was investigated by evaluating homotypic interactions with tumor cells and heterotypic adhesion to cancer-associated fibroblasts (CAFs). RNA delivery performance was assessed using Cy5-labelled siRNA-loaded LNPs.

The CCM-NGs preserved key membrane proteins and exhibited inherent tumor-mimicking properties. Uptake studies demonstrated time-dependent internalization of CCM-NGs, particularly in the CAF model, confirming efficient heterotypic adhesion. The biomimetic core–shell nanoparticles displayed improved tumor-targeting behavior, and siRNA delivery was significantly enhanced compared to uncoated LNPs.

Overall, this study highlights CCM-NG-coated LNPs as a promising strategy to strengthen tumor specificity and improve the therapeutic potential of RNA-based cancer treatments.