Ultrasound stimulated release and catalysis using polyelectrolyte multilayer capsules

Ultrasound has been used to trigger release of encapsulated material from polyelectrolyte multilayer capsules. Sonication was found to destroy both plain and nanoparticle-modified capsules. Cavitation occurs through the collapse of generated microbubbles and the resulting shear forces should cause the destruction of the polyelectrolyte capsules. Application in catalysis is demonstrated in this paper, while further potential usage of ultrasound triggered release is anticipated in bio-medical applications

Polymeric multilayer capsule-mediated vaccination induces protective immunity against cancer and viral infection

Recombinant antigens hold high potential to develop vaccines against lethal intracellular pathogens and cancer. However, they are poorly immunogenic and fail to induce potent cellular immunity. In this paper, we demonstrate that polymeric multilayer capsules (PMLC) strongly increase antigen delivery toward professional antigen-presenting cells in vivo, including dendritic cells (DCs), macrophages, and B cells, thereby enforcing antigen presentation and stimulating T cell proliferation. A thorough analysis of the T cell response demonstrated their capacity to induce IFN-gamma secreting CD4 and CD8 T cells, in addition to follicular T-helper cells, a recently identified CD4 T cell subset supporting antibody responses. On the B cell level, PMLC-mediated antigen delivery promoted the formation of germinal centers, resulting in increased numbers of antibody-secreting plasma cells and elevated antibody titers. The functional relevance of the induced immune responses was validated in murine models of influenza and melanoma. On a mechanistic level, we have demonstrated the capacity of PMLC to activate the NALP3 inflammasome and trigger the release of the potent pro-inflammatory cytokine IL-1 beta. Finally, using DC-depleted mice, we have identified DCs as the key mediators of the immunogenic properties of PMLC

Single-step formation of degradable intracellular biomolecule microreactors

Here we present a single-step all-aqueous approach to encapsulate biomolecules such as enzymes and proteins into stable microreactors. Key In this method is the use of spray-drying of the biomolecules of interest in combination with oppositely. charged,polyelectrolytes and mannitol as the sacrificial template. Remarkably, upon spray-drying in the presence of polyelectrolyte, mannitol crystallization is suppressed and the obtained amorphous mannitol offers enhanced preservation of the biomolecules' activity. Moreover, the use of mannitol allows the formation of nanopores within the microparticles upon rehydration of the microparticles in aqueous medium and subsequent dissolution, of the mannitol. The oppositely charged polyelectrolytes provide a polymeric framework which stabilizes the microparticles upon rehydration. The versatility of this approach Is demonstrated using horseradish peroxidase as the model enzyme and ovalbumin as the model antigen

Feasibility of mechanical extrusion to coat nanoparticles with extracellular vesicle membranes

Abstract Biomimetic functionalization to confer stealth and targeting properties to nanoparticles is a field of intense study. Extracellular vesicles (EV), sub-micron delivery vehicles for intercellular communication, have unique characteristics for drug delivery. We investigated the top-down functionalization of gold nanoparticles with extracellular vesicle membranes, including both lipids and associated membrane proteins, through mechanical extrusion. EV surface-exposed membrane proteins were confirmed to help avoid unwanted elimination by macrophages, while improving autologous uptake. EV membrane morphology, protein composition and orientation were found to be unaffected by mechanical extrusion. We implemented complementary EV characterization methods, including transmission- and immune-electron microscopy, and nanoparticle tracking analysis, to verify membrane coating, size and zeta potential of the EV membrane-cloaked nanoparticles. While successful EV membrane coating of the gold nanoparticles resulted in lower macrophage uptake, low yield was found to be a significant downside of the extrusion approach. Our data incentivize more research to leverage EV membrane biomimicking as a unique drug delivery approach in the near future

Spray-dried polyelectrolyte microparticles in oral antigen delivery : stability, biocompatibility and cellular uptake

During the past decade, extensive research has undeniably improved the formulation and delivery of oral vaccines. Nevertheless, several factors, such as the harsh gastrointestinal environment together with tolerance induction to exogenous antigens, have thus far impeded the optimal effectiveness and clinical application of oral delivery systems. The current study encompasses an initial evaluation of the stability, biocompatibility and cellular uptake of two promising candidate systems for oral antigen delivery, i.e. calcium carbonate- (CP) and mannitol-templated (MP) porous microspheres. Both spray-dried formulations were efficiently internalized by human intestinal epithelial cells (Caco-2 and HT-29) and degraded into phagolysosomal intracellular compartments. In addition, cellular particle uptake and processing significantly up-regulated the expression of (HLA) class-II and costimulatory molecules on intestinal epithelial cells. Even though the high surface-area-to-volume ratio of the microspheres were expected to favor protease access, antigen release was remarkably limited in simulated intestinal fluid and was even absent under gastric conditions. Finally, CP nor MP exerted cytotoxicity upon prolonged in vitro incubation with high antigen concentration. Altogether, these data support the potential of CP and MP for oral antigen delivery and motivate the further development of these promising carrier systems in in vivo studies

Salt Plays a Pivotal Role in the Temperature-Responsive Aggregation and Layer-by-Layer Assembly of Polymer-Decorated Gold Nanoparticles

We report that the aqueous self-assembly behavior of citrate based gold nanoparticles decorated with the temperature responsive RAFT-based polymer poly(N-isopropylacrylamide) critically depends on the presence of salt in the medium. Both for temperature induced reversible agglomeration and for hydrogen bonding based layer-by-layer assembly with tannic acid, the presence of salt dramatically promotes the assembly behavior. We attribute this to a combination of ionic screening of the remaining citrate groups on the nanoparticle surface and a salting out effect which increases the contribution of hydrophobic interactions in the self-assembly process. These findings provide new insights into an attractive class of polymer/gold hybrid nanomaterials that can find application in biotechnology, catalysis, and biomedicine