Search

Inthe last decades, the number of allergic patients has increaseddramatically. Allergen-specific immunotherapy (SIT) is the only availablecause-oriented therapy so far. SIT reduces the allergic symptoms,but also exhibits some disadvantages; that is, it is a long-lastingprocedure and severe side effects like anaphylactic shock can occur.In this work, we introduce a method to encapsulate allergens intonanoparticles to avoid severe side effects during SIT. Degradablenanocarriers combine the advantage of providing a physical barrierbetween the encapsulated cargo and the biological environment as wellas responding to certain local stimuli (like pH) to release theircargo. This work introduces a facile strategy for the synthesis ofacid-labile poly(ethylene glycol) (PEG)-macromonomers that degradeat pH 5 (physiological pH inside the endolysosome) and can be usedfor nanocarrier synthesis. The difunctional, water-soluble PEG dimethacrylate(PEG-acetal-DMA) macromonomers with cleavable acetal units were analyzedwith 1H NMR, SEC, and MALDI-ToF-MS. Both the allergen andthe macromonomers were entrapped inside liposomes as templates, whichwere produced by dual centrifugation (DAC). Radical polymerizationof the methacrylate units inside the liposomes generated allergen-loadedPEG nanocarriers. In vitro studies demonstrated that dendritic cells(DCs) internalize the protein-loaded, nontoxic PEG-nanocarriers. Furthermore,we demonstrate by cellular antigen stimulation tests that the nanocarrierseffectively shield the allergen cargo from detection by immunoglobulinson the surface of basophilic leucocytes. Uptake of nanocarriers intoDCs does not lead to cell maturation; however, the internalized allergenwas capable to induce T cell immune responses. [ABSTRACT FROM AUTHOR]