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Data · dataset · 2026

Karlah Mansauda: Overcoming the PEGylation Dilemma in Lipid Nanoparticles for CD47 Silencing: Enhanced Macrophage-Mediated Tumour Clearance

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Description

Background

Silencing CD47, a “don’t eat me” signal on breast cancer cells, with small interfering RNA (siRNA), restores macrophage-mediated phagocytosis. Lipid nanoparticles (LNPs) deliver siRNA, but the stabilising PEG layer tends to trap them in endosomes (pH <6) (the PEGylation dilemma). We aim to develop acid-cleavable PEG-lipid LNP (PEGCL-LNP/siCD47) that will ‘shed’ in acidic endosomes.

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Methods

PEGCL-LNP/siCD47 and non-cleavable controls were formulated and characterised for physicochemical properties, viability, silencing efficiency, and phagocytosis activity. <br>Results: NMR confirmed PEGb-Hz-DPPE. Controls LNP/siCD47 size measured ~150 nm with >80% encapsulation. siRNA above 10 nM reduced cell viability. CD47 silencing reached ~60%; phagocytosis was confirmed; however, endosomal escape was minimal.

PEGCL-LNP/siCD47’s size is larger (~240 nm), PDI (~0.39) and zeta potential (~1.0 mV). Studies on PEG-cleavable LNPs are ongoing. Conclusion: Non-cleavable LNP/siCD47 showed slow transfection (48 h), possibly due to endosomal entrapment.

Ongoing F2-based PEGCL-LNP/siCD47 is expected to improve endosomal escape, CD47 silencing and phagocytosis.</p>

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Where it is published

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Cancer 75%
Provenance · 1 source records, 9 field assertions
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