Advanced materials (Deerfield Beach, Fla.)Jul 14, 2026

Using Lipid Nanoparticles to Deliver mRNA and a Drug Together for Oral Cancer Chemoimmunotherapy

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 15, 2026

Abstract

The overall incidence rate of oral squamous cell carcinoma (OSCC) is projected to increase by 30% in the next 10 years.

OSCC accounts for 90% of all head and neck cancers with a 5-year survival rate of 50%.
Progression of OSCC is linked to inactivation and mutation of tumor suppressor genes.
The tumor microenvironment of OSCC is characterized as 'cold,' which poses treatment challenges.
A lipid nanoparticle co-encapsulating p53 mRNA and ciclopirox demonstrates innate chemotherapeutic properties.
This combination therapy may reduce immunosuppression in the tumor microenvironment by altering the behavior of tumor-associated macrophages.
The platform shows potential effectiveness across different OSCC models, including those resistant to p53 therapies.

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%. Strikingly, the overall incidence rate is projected to increase by 30% in the next 10 years, which may result in a sharp increase in mortality. Two fundamental aspects of OSCC are that it progresses via the inactivation and mutation of tumor suppressor genes (TSGs) and has a "cold" tumor microenvironment (TME). 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 TME 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 offers a template for a delivery platform capable of tackling multiple mechanisms of OSCC progression and survival.

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Using Lipid Nanoparticles to Deliver mRNA and a Drug Together for Oral Cancer Chemoimmunotherapy

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