Enzyme-Triggered Release of the Antisense Octaarginine-PNA Conjugate from Phospholipase A2 Sensitive Liposomes
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Enzyme-Triggered Release of the Antisense Octaarginine-PNA Conjugate from Phospholipase A2 Sensitive Liposomes. / Ghavami, Mahdi; Shiraishi, Takehiko; Nielsen, Peter E.
I: ACS Applied Bio Materials, Bind 3, Nr. 2, 2020, s. 1018-1025.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Enzyme-Triggered Release of the Antisense Octaarginine-PNA Conjugate from Phospholipase A2 Sensitive Liposomes
AU - Ghavami, Mahdi
AU - Shiraishi, Takehiko
AU - Nielsen, Peter E.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - antisense PNA
KW - drug delivery
KW - liposomes
KW - phospholipase A2
KW - phospholipase-triggered release
KW - protein corona
U2 - 10.1021/acsabm.9b01022
DO - 10.1021/acsabm.9b01022
M3 - Journal article
AN - SCOPUS:85080089988
VL - 3
SP - 1018
EP - 1025
JO - ACS Applied Bio Materials
JF - ACS Applied Bio Materials
SN - 2576-6422
IS - 2
ER -
ID: 237413914