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

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 (P-Arg), which is cleavable by trypsin, was carried out over a negatively charged liposome. The enzymatic cleavage of P-Arg 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 (P-Glu) and an outer layer consisting of trypsin and P-Arg onto the liposome. The degradation of the outer P-Arg by trypsin allowed the surface to display the inner P-Glu, which has bone-targeting ability. In addition, the polymer wall was constructed from an inner layer of P-Arg and an outer layer of pepsin and P-Glu. The degradation of the outer P-Glu by pepsin led to inner P-Arg on the surface to achieve cell-penetrating activity.