Complexity, unpredictability and safety challenges of lipid nanoparticles

A multidisciplinary narrative review by Gutschi & Seger, 2025

https://www.researchgate.net/publication/396321059_Complexity_unpredictability_and_safety_challenges_of_lipid_nanoparticles_-A_multidisciplinary_narrative_review

The Offsc℞ipt Pharmacist

and me are thrilled to announce the publication of our first review, where we explore, from multiple perspectives, why the intrinsic nature of lipid nanoparticles (LNPs) is inherently unpredictable and why this biologically active technology triggers complex, deep, unforeseen cellular interactions.¹

We examine the biocorona, clarify why the phrase “goes everywhere in the body” oversimplifies the true behavior of LNPs, and highlight critical research gaps that warrant a moratorium. We raise concerns about the uncertainty surrounding which receptors are internalized, activated, or influenced by interactions with lipid rafts.

Another important aspect we bring on the table is the journey of the LNPs.

Furthermore, we address the challenge of identifying which “target cells” are transfected.

Moreover, we adress basic issues on tracking LNPs in vivo.

Our review synthesizes insights from over 160 peer-reviewed studies and will be available as a preprint on Authorea in the coming days.

1. https://www.researchgate.net/publication/396321059_Complexity_unpredictability_and_safety_challenges_of_lipid_nanoparticles_-A_multidisciplinary_narrative_review