Peptide anchor for folate-targeted liposomal delivery

NOGUEIRA EUGENIA; MANGIALAVORI IRENE; LOUREIRO ANA; SARRIA MARISA P.; NOGUEIRA PATRÍCIA ; FREITAS JAIME; HANRMARK JOHAN; ULYANA SHIMANOVICH; ROLLETT ALEXANDRA ; LACROIX GHISLAINE; BERNARDES GONZALO J. L.; GUEBITZ GEORG ; HEBERT HANS ; MOREIRA ALEXANDRA ; CARMO, ALEXANDRE M. ; ROSSI JUAN PABLO F. C. ; ANDREIA C. GOMES; PRETO ANA ; CAVACO-PAULO ARTUR

BIOMACROMOLECULES

AMER CHEMICAL SOC

Lugar: Washington; Año: 2015 vol. 10 p. 2904 - 2910

1525-7797

The folate receptor is abundantly over-expressed in chronically activated macrophages from patients with rheumatoid arthritis as well as in cancer cells1. Folate receptor targeting with liposomes is usually performed using folate, polyethylene glycol and a phospholipid or cholesterol anchor2-4. Here, we present an innovative strategy for targeted liposomal delivery that uses a hydrophobic fragment of surfactant protein D conjugated to a linker and folate. The peptide conjugate inserts deeply into the lipid bilayer without affecting liposomal integrity. The novel liposomal constructs are highly stable, efficient and specific for the folate receptor both in vitro and in vivo. This liposomal formulation significantly increases the clinical benefit of the encapsulated drug methotrexate in vivo in a mouse model of arthritis. These liposomes functionalised with hydrophobic peptide-tailed folate therefore constitute a novel and powerful system for efficient and safe drug delivery in folate receptor overexpressing diseases.