Controlled release and targeting of polypeptide-deposited liposomes by enzymatic degradation

Yuuka Fukui, Hikari Otsuka, Keiji Fujimoto

Research output: Contribution to journalArticle

Abstract

We prepared biobased nanocapsules with enzymatic degradability, which were generated by the layer-by-layer deposition of enzymes and polypeptide over the liposomal surface. Here, we demonstrate two different systems based on the enzymatic degradation of polymer layers. First, the deposition of trypsin and polyarginine (PArg), which is cleavable by trypsin, was carried out over a negatively charged liposome. The enzymatic cleavage of PArg resulted in exposure of the lipid membrane, which facilitated release of the cargo. Next, we attempted to degrade the outer polymer layer of the multilayered capsule wall to display the inner polymer layer by enzymatic degradation. This approach enabled the accumulation and targeting of the nanocapsules through the affinity between the displayed polymer layer and the target hydroxyapatite (HAp). The polymer wall was constructed with an inner layer consisting of poly-L-glutamic acid (PGlu) and an outer layer consisting of trypsin and PArg onto the liposome. The degradation of the outer PArg by trypsin allowed the surface to display the inner PGlu, which has bone-targeting ability. In addition, the polymer wall was constructed from an inner layer of PArg and an outer layer of pepsin and PGlu. The degradation of the outer PGlu by pepsin led to inner PArg on the surface to achieve cell-penetrating activity.

Original languageEnglish
JournalPolymer Journal
DOIs
Publication statusPublished - 2019 Jan 1

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Liposomes
Polypeptides
Polymers
Degradation
Trypsin
Peptides
Glutamic Acid
Nanocapsules
Acids
Pepsin A
Durapatite
Membrane Lipids
Hydroxyapatite
Capsules
polyarginine
Bone
Enzymes

ASJC Scopus subject areas

  • Polymers and Plastics
  • Materials Chemistry

Cite this

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title = "Controlled release and targeting of polypeptide-deposited liposomes by enzymatic degradation",
abstract = "We prepared biobased nanocapsules with enzymatic degradability, which were generated by the layer-by-layer deposition of enzymes and polypeptide over the liposomal surface. Here, we demonstrate two different systems based on the enzymatic degradation of polymer layers. First, the deposition of trypsin and polyarginine (PArg), which is cleavable by trypsin, was carried out over a negatively charged liposome. The enzymatic cleavage of PArg resulted in exposure of the lipid membrane, which facilitated release of the cargo. Next, we attempted to degrade the outer polymer layer of the multilayered capsule wall to display the inner polymer layer by enzymatic degradation. This approach enabled the accumulation and targeting of the nanocapsules through the affinity between the displayed polymer layer and the target hydroxyapatite (HAp). The polymer wall was constructed with an inner layer consisting of poly-L-glutamic acid (PGlu) and an outer layer consisting of trypsin and PArg onto the liposome. The degradation of the outer PArg by trypsin allowed the surface to display the inner PGlu, which has bone-targeting ability. In addition, the polymer wall was constructed from an inner layer of PArg and an outer layer of pepsin and PGlu. The degradation of the outer PGlu by pepsin led to inner PArg on the surface to achieve cell-penetrating activity.",
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AB - We prepared biobased nanocapsules with enzymatic degradability, which were generated by the layer-by-layer deposition of enzymes and polypeptide over the liposomal surface. Here, we demonstrate two different systems based on the enzymatic degradation of polymer layers. First, the deposition of trypsin and polyarginine (PArg), which is cleavable by trypsin, was carried out over a negatively charged liposome. The enzymatic cleavage of PArg resulted in exposure of the lipid membrane, which facilitated release of the cargo. Next, we attempted to degrade the outer polymer layer of the multilayered capsule wall to display the inner polymer layer by enzymatic degradation. This approach enabled the accumulation and targeting of the nanocapsules through the affinity between the displayed polymer layer and the target hydroxyapatite (HAp). The polymer wall was constructed with an inner layer consisting of poly-L-glutamic acid (PGlu) and an outer layer consisting of trypsin and PArg onto the liposome. The degradation of the outer PArg by trypsin allowed the surface to display the inner PGlu, which has bone-targeting ability. In addition, the polymer wall was constructed from an inner layer of PArg and an outer layer of pepsin and PGlu. The degradation of the outer PGlu by pepsin led to inner PArg on the surface to achieve cell-penetrating activity.

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