5 research outputs found
Glutathione Responsive Hyaluronic Acid Nanocapsules Obtained by Bioorthogonal Interfacial “Click” Reaction
Azide-functionalized hyaluronic acid
and disulfide dialkyne have
been used for “click” reaction polymerization at the
miniemulsion droplets interface leading to glutathione responsive
nanocapsules (NCs). Inverse miniemulsion polymerization was chosen,
due to its excellent performance properties, for example, tuning of
size and size distribution, shell thickness/density, and high pay
loading efficiency. The obtained size, size distribution, and encapsulation
efficiency were checked via fluorescent spectroscopy, and the tripeptide
glutathione was used to release an encapsulated fluorescent dye after
cleavage of the nanocapsules shell. To show the glutathione-mediated
intracellular cleavage of disulfide-containing NC shells, CellTracker
was encapsulated into the nanocapsules. The cellular uptake in dendritic
cells and the cleavage of the nanocapsules in the cells were studied
using confocal laser scanning microscopy. Because of the mild reaction
conditions used during the interfacial polymerization and the excellent
cleavage properties, we believe that the synthesis of glutathione
responsive hyaluronic acid NCs reported herein are of high interest
for the encapsulation and release of sensitive compounds at high yields
Additional file 4: of Dendritic cells change IL-27 production pattern during childhood
Figure S4. Age related frequencies of IL-27-positive mDCs (top row) and pDCs (lower row)
Additional file 3: of Dendritic cells change IL-27 production pattern during childhood
Figure S3. Age-related cell frequency
Enhanced in Vivo Targeting of Murine Nonparenchymal Liver Cells with Monophosphoryl Lipid A Functionalized Microcapsules
A broad spectrum of infectious liver
diseases emphasizes the need
of microparticles for targeted delivery of immunomodulatory substances
to the liver. Microcapsules (MCs) are particularly attractive for
innovative drug and vaccine formulations, enabling the combination
of antigen, drugs, and adjuvants. The present study aimed to develop
microcapsules characterized by an enhanced liver deposition and accelerated
uptake by nonparenchymal liver cells (NPCs). Initially, two formulations
of biodegradable microcapsules were synthesized from either hydroxyethyl
starch (HES) or mannose. Notably, HES-MCs accumulated primarily in
the liver, while mannose particles displayed a lung preference. Functionalization
of HES-MCs with anti-CD40, anti-DEC205, and/or monophosphoryl lipid
A (MPLA) enhanced uptake of MCs by nonparenchymal liver cells in vitro.
In contrast, only MPLA-coated HES-MCs promoted significantly the in
vivo uptake by NPCs. Finally, HES-MCs equipped with MPLA, anti-CD40,
and anti-DEC205 induced the secretion of TNF-α, IL-6 by Kupffer
cells (KCs), and IFN-γ and IL-12p70 by liver dendritic cells
(DCs). The enhanced uptake and activation of KCs by MPLA-HES-MCs is
a promising approach to prevent or treat infection, since KCs are
exploited as an entry gate in various infectious diseases, such as
malaria. In parallel, loading and activating liver DCs, usually prone
to tolerance, bears the potential to induce antigen specific, intrahepatic
immune responses necessary to prevent and treat infections affecting
the liver
DataSheet1_Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice.docx
Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency in functional phenylalanine hydroxylase (PAH), resulting in accumulation of phenylalanine (Phe) in patients’ blood and organs. Affected patients encounter severe developmental delay, neurological deficits, and behavioral abnormalities when not treated. Early diagnosis and treatment are extremely important; newborn screening programs have been implemented in most countries to ensure early identification of patients with PKU. Despite available treatment options, several challenges remain: life-long adherence to a strict diet, approval of some medications for adults only, and lack of response to these therapies in a subpopulation of patients. Therefore, there is an urgent need for treatment alternatives. An mRNA-based approach tested in PKU mice showed a fast reduction in the accumulation of Phe in serum, liver and brain, the most significant organ affected. Repeated injections of LNP-formulated mouse PAH mRNA rescued PKU mice from the disease phenotype for a prolonged period of time. An mRNA-based approach could improve the quality of life tremendously in PKU patients of all ages by replacing standard-of-care treatments.</p