Science advancesOct 24, 2025

Special lipid nanoparticles with guanidine groups for targeted mRNA delivery and cancer immune treatment

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Guanidine-based lipid nanoparticles may improve organ-targeted mRNA delivery for cancer immunotherapy.

Evidence

This formulation/platform experiment tested cholesterol-free pH-responsive guanidine LNPs for mRNA delivery, showing spleen and antigen-presenting-cell targeting, stronger antigen presentation and T cell activation, tumor-progression protection, and pancreas expression after intraperitoneal dosing.

Caveat

The abstract does not specify the model, sample size, safety profile, or durability, so the findings do not establish clinical performance.

Simplified

The development of lipid nanoparticle (LNP) systems has largely advanced RNA therapeutics, particularly mRNA-based cancer immunotherapy. Conventional amine-LNPs, designed for hepatic RNA delivery, face challenges in targeting lymphoid organs effectively and maximize antigen presentation. In this study, we present the development of pH-responsive ionizable guanidine-LNPs (G-LNPs). Our cholesterol-free G-LNP system enables efficient delivery of mRNA to the spleen following intravenous administration. Notably, while both amine-LNPs and G-LNPs can deliver mRNA to the spleen, G-LNPs exhibit a unique ability to preferentially target antigen-presenting cells, leading to significantly enhanced antigen presentation and robust T cell activation. mRNA vaccines formulated with G-LNPs elicited strong and antigen-specific immune responses, providing complete protection against tumor progression. In addition, intraperitoneal administration of G-LNPs enabled selective mRNA expression in the pancreas, showcasing the versatility of this delivery platform. These findings underscore the potential of guanidine-LNPs as a highly promising platform for organ-targeted mRNA delivery and cancer immunotherapy.

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Funding

Competing interests

H.Z., D.L., Z.L., and M.L. are inventors on a patent related to this work filed by Shenzhen Bay Laboratory (no. ZL202311752992.9, filed [20 December 2023], published [19 April 2024]). The authors declare that they have no other competing interests.

PubMed

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Special lipid nanoparticles with guanidine groups for targeted mRNA delivery and cancer immune treatment

Abstract

Full Text

Funding

Competing interests

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