2026-10-06T20:26:04Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34004574 2026-09-30T00:20:15Z category_24859 portal_12 item_type_5 month_year_09_2026

Karlah Mansauda: Overcoming the PEGylation Dilemma in Lipid Nanoparticles for CD47 Silencing: Enhanced Macrophage-Mediated Tumour Clearance Karlah Mansauda (22111300) Kamel Ahmed (14379108) Mahnoor Ahmad (20607020) Patrick Pan (6689555) Emma Nolan (12056093) Zimei Wu (1222443) Pharmaceutical delivery technologies CD47 siRNA Lipid Nanoparticles PEGylation Dilemma Breast Cancer <p dir="ltr">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. 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> 2026-09-30T00:20:15Z Image Poster 10.17608/k6.auckland.34004574.v2 https://figshare.com/articles/poster/Overcoming_the_PEGylation_Dilemma_in_Lipid_Nanoparticles_for_CD47_Silencing_Enhanced_Macrophage-Mediated_Tumour_Clearance/34004574 CC BY 4.0