Forskning ved Københavns Universitet - Københavns Universitet


Enzyme-Triggered Release of the Antisense Octaarginine-PNA Conjugate from Phospholipase A2 Sensitive Liposomes

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Phospholipase sensitive liposomes (PSLs) have attracted great attention in targeted anticancer drug delivery due to cargo release triggered by tumor-secreted phospholipase A2 (sPLA2). Such liposomes could also serve as a vehicle for tissue-specific delivery of antisense therapeutics to (solid) tumors. While extensive studies on developing PSL formulations for small molecules exist, hardly any data are available on delivering larger molecules such as antisense agents. The present study demonstrates PSL encapsulation and phospholipase A2 triggered the release of a splice correcting, antisense octaarginine-peptide nucleic acid (octaarginine-PNA) conjugate. The results show that, although PNA can be efficiently encapsulated in PSL and also released using sPLA2 in serum-free conditions, the release is inhibited in the presence of serum. This is ascribed to the adsorption of serum proteins, including serum albumin and apolipoprotein C-III, to the surface of PSL (corona formation) and consequent prevention of sPLA2-mediated PNA release.

TidsskriftACS Applied Bio Materials
Udgave nummer2
Sider (fra-til)1018-1025
Antal sider8
StatusUdgivet - 2020

ID: 237413914