Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs

Abstract

β-lactam antibiotics (BLs) are the drugs most frequently involved in drug hypersensitivity reactions. However, current in vitro diagnostic tests have limited sensitivity, partly due to a poor understanding of in vivo drug–protein conjugates that both induce the reactions and are immunologically recognized. Dendrimeric Antigen-Silica particle composites (DeAn@SiO2), consisting on nanoparticles decorated with BL-DeAns are promising candidates for improving the in vitro clinical diagnostic practice. In this nano-inspired system biology, the synthetic dendrimer plays the role of the natural carrier protein, emulating its haptenation by drugs and amplifying the multivalence. Herein, we present the design and synthesis of new multivalent mono- and bi-epitope DeAn@SiO2, using amoxicillin and/or benzylpenicillin allergenic determinants as ligands. The homogeneous composition of nanoparticles provides high reproducibility and quality, which is critical for in vitro applications. The suitable functionalization of nanoparticles allows the anchoring of DeAn, minimizing the nonspecific interactions and facilitating the effective exposure to specific IgE; while the larger interaction area increments the likelihood of capturing specific IgE. This achievement is particularly important for improving sensitivity of current immunoassays since IgE levels in BL allergic patients are very low. Our data suggest that these new nano-based platforms provide a suitable tool for testing IgE recognition to more than one BL simultaneously. Immunochemical studies evidence that mono and bi-epitope DeAn@SiO2 composites could potentially allow the diagnosis of patients allergic to any of these drugs with a single test. These organic–inorganic hybrid materials represent the basis for the development of a single screening for BL-allergies.

Biomarkers of immediate drug hypersensitivity

“…On the other hand, great efforts are being made in the implementation of more sensitive detection methods by using ultra-sensitive chemiluminescence immunoassay, 39 and a multiplex microimmunoassay, 40 with traditional cellulose discs (83% for AX, 78% for BP), and interestingly, the detection of false-positive results of BP sIgE for confirmed AX-selective patients decreased from 41% for cellulose discs to 0% for nanoparticles. 41 This method provides high reproducibility due to the homogeneous composition of nanoparticles and facilitates the effective exposure of drugs to sIgE improving sensitivity.…”

Drug hypersensitivity, in vitro tools, biomarkers, and burden with COVID‐19 vaccines

“…On the contrary, silica nanoparticles decorated with betalactam (BL) antigenic determinants were reported for their use as a solid phase in immunoassays (radioallergosorbent test [RAST]) for the detection of BLs‐sIgE in sera from patients by 15 improving the sensitivity and specificity compared with the conventional RAST using poly‐L‐lysine as carrier molecule. These silica nanoparticles had a diameter around 500 nm, and a Generation 2 Poly(amidoamine) (PAMAM G2) dendrimer was first grafted to the surface of the silica nanoparticles (forming amide bonds between amino groups in the dendrimer and carboxylic acid groups on the silica surface).…”

“…In this way, these nanoparticles mimic the carrier protein‐drug hapten complex, which is then used as the solid phase in immunoassays or as the stimulatory component in cell‐based in vitro tests (Figure 2A). Some recent works highlight the potential impact of this strategy 2,15 …”

“…Some recent works highlight the potential impact of this strategy. 2,15 Thus, liposomes containing either an oxaliplatin-lipid or a carboplatin-lipid have been developed for diagnosing platin salts hypersensitivity. 2 These liposomes had a diameter of 400 nm, and the drug was attached to one of the lipids in the formulation, which constituted 5% (molar percentage) of the total lipid content.…”

“…Although after the initial round of vaccination against COVID-19, it was believed that IHSRs could be a common problem, the majority In vitro tools Nanoparticles-allergen for detection of HSRs to drugs. 2,15 To develop diagnostic methods for allergic diseases based on nanoparticles Increase in the BAT sensitivity in HSRs to drugs. 3,[17][18][19][20][21] To improve the specificity and sensitivity of in vitro methods for allergic diseases LTT using DC improve the sensitivity of test and the proliferative response of effector cells.…”