Adenoviruses Encapsulated in PEGylated DOTAP-Folate Liposomes Are Protected from the Pre-Existing Humoral Immune Response
Year: 2025
Type: article
Abstract: Background/Objectives: While adenovirus (Ad) therapies have been proven to be effective in local administration, systemic Ad treatments have shown limited success due to pre-existing antibodies in the human blood that neutralize the virus. We developed a liposome coating procedure that protects the Ad from pre-existing neutralizing antibodies in human blood. To assess the in vivo stability of the liposomes, the present study used a novel in vivo method to quantitatively assess the protective capabilities of liposome-encapsulated Ad (DfAd) from neutralizing antibodies. Methods: The assay systemically administers DfAd with a green fluorescent protein transgene (DfAd-GFP) into pre-immunized mice and allows it to circulate in the presence of neutralizing antibodies; the infected blood is extracted and used to transduce HEK293 cells, which emits fluorescence in the presence of protected, un-neutralized Ad. Results: The PEGylated liposome formulation provides 12× protection in vivo relative to unencapsulated Ads. In vitro optimization of the liposome coating reveals a strong correlation between the structural stability of liposomes and protection against anti-Ad neutralizing antibodies, where DSPE-PEG2000-carboxylic acid (DSPE-PEG2000-CA) is a critical component for liposome stability and increasing protection against antibody neutralization of the encapsulated Ad. Conclusions: The findings in the present study confirm that the DfAd liposome can protect against neutralizing antibodies in blood circulation. The novel in vivo assay for liposome protection against neutralizing antibodies and in vitro experiments in the present study provide new tools and insights toward designing liposome–Ad complexes for the systemic treatment of cancer.
Source: Pharmaceutics
Institutions: University of California San Diego, Moores Cancer Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Funders: National Science Foundation, UC Irvine Materials Research Institute, University of California, San Diego, University of California, Irvine, Materials Research Science and Engineering Center, Harvard University, National Cancer Institute, Division of Materials Research, Materials Research Science and Engineering Center, University of California, San Diego
Awards: G100008966, G1135980590, G1186292489, G196843582, UCI MRSEC: Materials Discovery Through Atomic Level Structural Design and Charge Control, G2593733834, G4228951661, G5282220012, UC San Diego MRSEC: an NSF Materials Research Science and Engineering Center, G8412107296, G8692219177, G97908232
OpenAlex ID: W4411210650