The induction of a strong cytotoxic T cell response is an important prerequisite for successful immunotherapy against many viral diseases and tumors. Nucleotide vaccines, including mRNA vaccines with their intracellular antigen synthesis, have been shown to be potent activators of a cytotoxic immune response. The intracellular delivery of mRNA vaccines to the cytosol of antigen presenting immune cells is still not sufficiently well understood. Here, we report on the development of a lipid nanoparticle formulation for the delivery of mRNA vaccines to induce a cytotoxic CD 8 T cell response. We show transfection of dendritic cells, macrophages, and neutrophils. The efficacy of the vaccine was tested in an aggressive B16F10 melanoma model. We found a strong CD 8 T cell activation after a single immunization. Treatment of B16F10 melanoma tumors with lipid nanoparticles containing mRNA coding for the tumor-associated antigens gp100 and TRP2 resulted in tumor shrinkage and extended the overall survival of the treated mice. The immune response can be further increased by the incorporation of the adjuvant LPS. In conclusion, the lipid nanoparticle formulation presented here is a promising vector for mRNA vaccine delivery, one that is capable of inducing a strong cytotoxic T cell response. Further optimization, including the incorporation of different adjuvants, will likely enhance the potency of the vaccine.
mRNA vaccines elicit a potent immune response including antibodies and cytotoxic T cells. mRNA vaccines are currently evaluated in clinical trials for cancer immunotherapy applications, but also have great potential as prophylactic vaccines. Efficient delivery of mRNA vaccines will be key for their success and translation to the clinic. Among potential nonviral vectors, lipid nanoparticles are particularly promising. Indeed, lipid nanoparticles can be synthesized with relative ease in a scalable manner, protect the mRNA against degradation, facilitate endosomal escape, can be targeted to the desired cell type by surface decoration with ligands, and as needed, can be codelivered with adjuvants.
Breathable and waterproof membranes that self-seal damaged areas are prepared by modifying a poly(ether ester) membrane with an amphiphilic polymer co-network. The latter swells in water and the gel closes punctures. Damaged composite membranes remain water tight up to pressures of at least 1.6 bar. This material is useful for applications where water-vapor permeability, self-sealing properties, and waterproofness are desired, as demonstrated for a medical cooling device.
Implantable electronics address therapeutical needs of patients with electrical signaling dysfunctions such as heart problems, neurological disorders or hearing impairments. While standard electronics are rigid, planar and made of hard materials, their surrounding biological tissues are soft, wet and constantly in motion. These intrinsic differences in mechanical and chemical properties cause physiological responses that constitute a fundamental challenge to create functional long-term interfaces. Using soft and stretchable materials for electronic implants decreases the mechanical mismatch between implant and biological tissues. As a result, tissue damage during and after implantation is reduced, leading not only to an attenuated foreign body response, but also enabling completely novel applications. However, but for a few exceptions, soft materials are not sufficient to create long-term stable functional implants. In this work, we review recent progress in interfacing both the central (CNS) and peripheral nervous system (PNS) for long-term functional devices. The basics of soft and stretchable devices are introduced by highlighting the importance of minimizing physical as well as mechanical mismatch between tissue and implant in the CNS and emphasizing the relevance of an appropriate surface chemistry for implants in the PNS. Finally, we report on the latest materials and techniques that provide further electronic enhancements while reducing the foreign body reaction. Thus, this review should serve as a guide for creating long-term functional implants to enable future healthcare technologies and as a discussion on current ideas and progress within the field.
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