# Liposome‐Based Potential Vaccines Platforms that Are Noncytotoxic

**Authors:** Saida Mebarek, Killian Jacob, Carmela Ilaria Pierro, Davide Romanini, Michele Fiore

PMC · DOI: 10.1002/open.202500530 · ChemistryOpen · 2026-01-11

## TL;DR

This study introduces a safe, non-toxic liposome-based vaccine platform for cancer immunotherapy using engineered neoglycolipids.

## Contribution

A modular, noncytotoxic liposomal vaccine platform using bio-orthogonal chemistry for antigen delivery is proposed.

## Key findings

- Neoglycolipids bearing the Tn antigen were synthesized without detectable cytotoxicity.
- Stable liposomes were formed using palmitic acid and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine via freeze–thaw/extrusion.
- The platform offers a tunable and safe method for antigen delivery in cancer immunotherapy.

## Abstract

Synthetic vaccines represent a promising avenue in cancer immunotherapy by promoting targeted immune responses. Liposomal technologies have further advanced synthetic vaccinology by enabling the efficient delivery of tumor‐associated carbohydrate antigens. Despite this progress, the toxicity and reproducibility of such platforms remain underexplored. In this preliminary study, we synthesized a series of neoglycolipids bearing the Thomsen–Nouveau (Tn) antigen using bio‐orthogonal thiol–ene click chemistry. Here we present the results obtained using a set of neoglycolipids that were evaluated for their ability to self‐assemble into liposomal vesicles and for in vitro cytotoxicity. The resulting neoglycolipids exhibited no detectable cytotoxicity and formed stable liposomal structures when formulated with palmitic acid and 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine via a freeze–thaw/extrusion process. This early‐stage work presents a proof of concept for a tunable, liposomal‐based synthetic vaccine platform.

Engineered neoglycolipids were formulated with palmitic acid and 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine into stable, noncytotoxic liposomes using a freeze–thaw/extrusion method. This proof‐of‐concept study demonstrates a modular liposomal vaccine platform, offering a safe and tunable carrier for antigen delivery, with potential applications in cancer immunotherapy.© 2026 WILEY‐VCH GmbH

## Linked entities

- **Chemicals:** palmitic acid (PubChem CID 985), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (PubChem CID 65167)
- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Diseases:** cytotoxicity (MESH:D064420), cancer (MESH:D009369)
- **Chemicals:** 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (MESH:C028694), palmitic acid (MESH:D019308), thiol (MESH:D013438), ene (-), carbohydrate (MESH:D002241)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12791030/full.md

## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC12791030/full.md

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Source: https://tomesphere.com/paper/PMC12791030