Cancer immune therapy using engineered ‛tail-flipping’ nanoliposomes targeting alternatively activated macrophages

Praneeth R. Kuninty, Karin Binnemars-Postma, Ahmed Jarray, Kunal P. Pednekar, Marcel A. Heinrich, Helen J. Pijffers, Hetty ten Hoopen, Gert Storm, Peter van Hoogevest, Wouter K. den Otter, Jai Prakash*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)
25 Downloads (Pure)


Alternatively-activated, M2-like tumor-associated macrophages (TAM) strongly contribute to tumor growth, invasiveness and metastasis. Technologies to disable the pro-tumorigenic function of these TAMs are of high interest to immunotherapy research. Here we show that by designing engineered nanoliposomes bio-mimicking peroxidated phospholipids that are recognised and internalised by scavenger receptors, TAMs can be targeted. Incorporation of phospholipids possessing a terminal carboxylate group at the sn-2 position into nanoliposome bilayers drives their uptake by M2 macrophages with high specificity. Molecular dynamics simulation of the lipid bilayer predicts flipping of the sn-2 tail towards the aqueous phase, while molecular docking data indicates interaction of the tail with Scavenger Receptor Class B type 1 (SR-B1). In vivo, the engineered nanoliposomes are distributed specifically to M2-like macrophages and, upon delivery of the STAT6 inhibitor (AS1517499), zoledronic acid or muramyl tripeptide, these cells promote reduction of the premetastatic niche and/or tumor growth. Altogether, we demonstrate the efficiency and versatility of our engineered “tail-flipping” nanoliposomes in a pre-clinical model, which paves the way to their development as cancer immunotherapeutics in humans.

Original languageEnglish
Article number4548
JournalNature communications
Issue number1
Early online date4 Aug 2022
Publication statusPublished - Dec 2022


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