Proceedings of the National Academy of Sciences of the United States of AmericaJun 23, 2026

Delivery of whole antibodies inside cells using organ-targeted fat-based nanoparticles

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Updated Jun 24, 2026

Abstract

A lipid nanoparticle platform can efficiently deliver therapeutic antibodies into cancer cell lines.

The platform enables selective inhibition of key transcription factors involved in inflammatory and cancer signaling pathways.
Therapeutic antibodies were successfully delivered systemically in disease models.
Specific applications included α-synuclein-targeting antibodies for Parkinson's disease and RelA-targeting Immunoglobulins for acute lung injury.
This method may aid in treating various intracellular disease targets by overcoming delivery challenges.

Simplified

Antibodies are proteins prized for their ability to bind to extracellular antigens with exceptionally high affinities and specificities. These features have motivated researchers to utilize antibody-antigen binding to inhibit intracellular disease targets in the proteome, yet delivery of antibodies into the cytosol of cells has long been a considerable challenge. Here, we outline the development of a lipid nanoparticle (LNP) platform for delivering antibodies into cells to selectively inhibit disease-relevant cytosolic targets. This approach efficiently delivers various therapeutic antibodies into multiple cancer cell lines, inhibiting key transcription factors in inflammatory and cancer signaling pathways. We further demonstrate systemic delivery of therapeutic antibodies in disease models, including α-synuclein-specific antibodies for Parkinson's disease and RelA-specific Immunoglobulins for acute lung injury using targeted LNP formulations. This work establishes a promising method for using LNPs for the delivery of antibody and antibody-derived therapeutics intracellularly to treat numerous proteome targets.

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Funding

Competing interests

Competing interests statement:A.A., M.P.D., and C.A.A. have financial interests in Cloaked Bio, Inc. M.P.D. also has financial interests in Gauntlet, Inc., June Bio APS, Glycobia Inc., Resilience, Inc., UbiquiTx Inc., and Versatope Therapeutics Inc. A.A.’s, M.P.D., and C.A.A. interests are reviewed and managed by Cornell University in accordance with their conflict-of-interest policy. All other authors declare no competing interests. A.A., M.P.D., and C.A.A. have filed a patent based on this work (Application # EP 4619038 A2).

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Delivery of whole antibodies inside cells using organ-targeted fat-based nanoparticles

Abstract

Full Text

Funding

Competing interests

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