Enzyme-Triggered Release of the Antisense Octaarginine-PNA Conjugate from Phospholipase A2 Sensitive Liposomes,ACS Applied Bio Materials

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Enzyme-Triggered Release of the Antisense Octaarginine-PNA Conjugate from Phospholipase A2 Sensitive Liposomes
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-01-30 , DOI: 10.1021/acsabm.9b01022
Mahdi Ghavami ₁ , Takehiko Shiraishi ₁ , Peter E Nielsen ₁

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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.

中文翻译：

从磷脂酶 A2 敏感脂质体中酶促释放反义八精氨酸-PNA 偶联物

_{由于由肿瘤分泌的磷脂酶 A 2} (sPLA ₂ )触发的货物释放，磷脂酶敏感性脂质体 (PSL) 在靶向抗癌药物递送中引起了极大的关注。这种脂质体也可以作为组织特异性向（实体）肿瘤递送反义治疗剂的载体。虽然存在关于开发小分子 PSL 制剂的广泛研究，但几乎没有任何数据可用于提供较大分子（如反义剂）。本研究表明 PSL 封装和磷脂酶 A ₂触发了剪接校正、反义八精氨酸-肽核酸 (octaarginine-PNA) 缀合物的释放。结果表明，虽然 PNA 可以有效地包裹在 PSL 中，也可以使用 sPLA 释放₂在无血清条件下，有血清存在时释放受到抑制。这归因于血清蛋白（包括血清白蛋白和载脂蛋白 C-III）吸附到 PSL 表面（电晕形成），从而阻止了 sPLA ₂介导的 PNA 释放。

更新日期：2020-01-31

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