Engineering Advanced Capsosomes: Maximizing the Number of Subcompartments, Cargo Retention, and Temperature-Triggered Reaction

Abstract

Advanced mimics of cells require a large yet controllable number of subcompartments encapsulated within a scaffold, equipped with a trigger to initiate, terminate, and potentially restart an enzymatic reaction. Recently introduced capsosomes, polymer capsules containing thousands of liposomes, are a promising platform for the creation of artificial cells. Capsosomes are formed by sequentially layering liposomes and polymers onto particle templates, followed by removal of the template cores. Herein, we engineer advanced capsosomes and demonstrate the ability to control the number of subcompartments and hence the degree of cargo loading. To achieve this, we employ a range of polymer separation layers and liposomes to form functional capsosomes comprising multiple layers of enzyme-loaded liposomes. Differences in conversion rates of an enzymatic assay are used to verify that multilayers of intact enzyme-loaded liposomes are assembled within a polymer hydrogel capsule. The size-dependent retention of the cargo encapsulated within the liposomal subcompartments during capsosome assembly and its dependence on environmental pH changes are also examined. We further show that temperature can be used to trigger an enzymatic reaction at the phase transition temperature of the liposomal subcompartments, and that the encapsulated enzymes can be utilized repeatedly in several subsequent conversions. These engineered capsosomes with tailored properties present new opportunities en route to the development of functional artificial cells.

Polyelectrolyte Multilayers in Tissue Engineering

“…Capsosomes are constructed from alternating layers of liposomes and an alternately charged polymer using LbL assembly. 130,131 The multiple liposome layers allow multiple reactions to occur simultaneously while being spatially separated within a single capsosome. 130 Another novel application of PEMs in drug delivery is the construction of multiple drug reservoirs within a single degradable PEM.…”

“…130,131 The multiple liposome layers allow multiple reactions to occur simultaneously while being spatially separated within a single capsosome. 130 Another novel application of PEMs in drug delivery is the construction of multiple drug reservoirs within a single degradable PEM. Drug reservoirs are constructed by exploiting the characteristic diffusivity associated only with exponentially growing PEMs, not normally observed under linear growth.…”

89Zr‐ and Fe‐Labeled Polymeric Micelles for Dual Modality PET and T1‐Weighted MR Imaging

“…capsosomes [ 8 ] to name only a few examples. New theranostic approaches are based on NPs that can carry a drug payload and also provide an imaging functionality that allows noninvasive imaging of the biodistribution or drug delivery process.…”

Application of nucleic acid–lipid conjugates for the programmable organisation of liposomal modules

“…These include careful assembly protocols for encapsulation of smaller vesicles within larger ones to create multicompartmental vesosomes [17][18][19], within layer-by-layer polymer shells [20][21][22], encapsulation of aqueous two phase systems within single liposomes [23][24][25] and association of lipid vesicles via site-specific ligand-receptor interactions such as biotin-avidin bonds [26][27][28]. Many of these approaches were discussed in a recent review [29].…”