bioRxiv : the preprint server for biologyNov 19, 2025

Using tiny fat-based particles to deliver mRNA and a small drug together for combined chemotherapy and immune therapy in oral cancer

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A lipid nanoparticle carrying p53 mRNA and ciclopirox showed a preclinical strategy for combining chemotherapy-like effects with immune microenvironment remodeling in OSCC models.

Evidence

A preclinical oral squamous cell carcinoma platform experiment co-encapsulated p53 mRNA and ciclopirox in lipid nanoparticles and tested caspase activation, tumor-associated macrophage repolarization, and activity in p53-therapy-susceptible and p53-therapy-resistant models.

Caveat

The abstract reports model-system efficacy and immune changes, but gives no clinical outcomes, survival data, or patient safety evidence.

Simplified

Oral squamous cell carcinoma (OSCC) represents 90% of all head and neck cancers. Despite decades of research, the 5-year survival rate is 50%, and strikingly, the overall incidence rate is projected to increase by 30% in the next ten years, which will result in a sharp increase in mortality. Two fundamental aspects of OSCC are that it progresses via the inactivation and mutation of tumor suppressor (TS) genes and has a "cold" tumor immune microenvironment (TIME). A major barrier in the treatment of OSCC is the lack of novel therapies clinicians have at their disposal that are designed to disrupt tumor progression by reshaping the cold tumors into inflammatory "hot" tumors. To overcome these obstacles, we employed a lipid nanoparticle (LNP) that co-encapsulates p53 mRNA and the small molecule ciclopirox (CPX). We demonstrate that both drugs have innate chemotherapeutic properties by facilitating caspase activation. Moreover, these therapies can create a less immunosuppressive TIME in part by repolarizing tumor-associated macrophages (TAMs) to M1-like phenotypes. When formulated together, our platform provides an all-in-one approach for OSCC, effective in both p53-therapy-susceptible and p53-therapy-resistant models. Additionally, this work provides a template for a delivery platform capable of tackling multiple mechanisms of OSCC progression and survival.