Purpose: In the bloodstream, nanoparticles (NPs) interact with serum proteins to form the protein corona, which includes both opsonins, promoting NP recognition and elimination, and dysopsonins, which can inhibit opsonin activity. Albumin, the most abundant serum protein, is part of this corona and can act as a dysopsonin, potentially hiding NPs from the immune system. This study aims to investigate how a covalently bound layer of human serum albumin (HSA) on polymeric NPs affects the protein corona and their behavior in the immune system. Methods: We covalently attached HSA to the surface of polymeric NPs to modify the protein corona composition. These HSA-covered nanostructures were then decorated with an anti-CD19 recombinant antibody fragment to target malignant B cells, specifically acute lymphoblastic leukemia (ALL) cells. The safety profile and bioavailability of these targeted HSA-nanoparticles were evaluated in vitro and in vivo using a human-zebrafish xenograft model of ALL. The efficacy of the nanostructures in delivering encapsulated doxorubicin and suppressing tumor growth was also assessed. Results: The HSA coating on polymeric NPs effectively modified the protein corona, preventing opsonization and subsequent macrophage-mediated elimination. The targeted HSA-nanoparticles maintained a safe profile with reduced macrophage interaction and specifically targeted tumor cells in the xenograft model. This resulted in the successful delivery of doxorubicin, tumor growth suppression, and increased survival of the model organisms. Conclusion: The study demonstrates that HSA-coated nanoparticles can be used as a therapeutic nanoplatform with a safe profile and enhanced bioavailability. The ability to decorate these nanostructures with specific targeting agents, such as anti-CD19 antibodies, opens up the potential for developing versatile therapeutic platforms that can be tailored to target various clinical conditions.

Nanoparticle-based therapies have been proposed in oncology research using various delivery methods to increase selectivity toward tumor tissues. Enhanced drug delivery through nanoparticle-based therapies could improve anti-tumor efficacy and also prevent drug resistance. However, there are still problems to overcome, such as the main biological interactions of nanocarriers. Among the various nanostructures for drug delivery, drug delivery based on polymeric nanoparticles has numerous advantages for controlling the release of biological factors, such as the ability to add a selective targeting mechanism, controlled release, protection of administered drugs, and prolonging the circulation time in the body. In addition, the functionalization of nanoparticles helps to achieve the best possible outcome. One of the most promising applications for nanoparticle-based drug delivery is in the field of onco-hematology, where there are many already approved targeted therapies, such as immunotherapies with monoclonal antibodies targeting specific tumor-associated antigens; however, several patients have experienced relapsed or refractory disease. This review describes the major nanocarriers proposed as new treatments for hematologic cancer, describing the main biological interactions of these nanocarriers and the related limitations of their use as drug delivery strategies.

The use of zebrafish (ZF) embryos as an in vivo model is increasingly attractive thanks to different features that include easy handling, transparency, and the absence of adaptive immunity until 4–6 weeks. These factors allow the development of xenografts that can be easily analyzed through fluorescence techniques. In this work, ZF were exploited to characterize the efficiency of drug-loaded polymeric NPs as a therapeutical approach for B-cell malignancies. Fluorescent probes, fluorescent transgenic lines of ZF, or their combination allowed to deeply examine biodistribution, elimination, and therapeutic efficacy. In particular, the fluorescent signal of nanoparticles (NPs) was exploited to investigate the in vivo distribution, while the colocalization between the fluorescence in macrophages and NPs allows following the elimination pathway of these polymeric NPs. Xenotransplanted human B-cells (Nalm-6) developed a reproducible model useful for demonstrating drug delivery by polymeric NPs loaded with doxorubicin and, as a consequence, the arrest of tumor growth and the reduction in tumor burden. ZF proved to be a versatile model, able to rapidly provide answers in the development of animal models and in the characterization of the activity and the efficacy of drug delivery systems.

Background/Objectives: A lifelong gluten-free diet (GFD) is the only treatment for celiac disease (CD). However, current methods for monitoring GFD adherence do not accurately assess gluten exposure. Stool detection of gluten immunogenic peptides (GIP) may provide an objective tool for detecting recent gluten exposure. The aim of this study was to evaluate stool GIP detection, compared with serology and the validated Biagi dietary questionnaire, for monitoring GFD adherence in children with CD. Methods: In this prospective multicenter study, pediatric patients with CD on a GFD for at least 1 year were enrolled. Serum and stool samples were collected on the same day to assess serum anti-transglutaminase (TTG) and anti-endomysium (EMA) antibodies and stool GIP. Patients also completed the Biagi dietary questionnaire. Results: Forty-one pediatric patients with CD on a GFD for a median of 6.5 years were enrolled. Serum TTG and/or EMA were positive in 8/41 patients (19.5%), Biagi questionnaire identified 8/41 patients (19.5%) as non-adherent, whereas stool GIP was positive in 17/41 (41.5%). Combining serology with the dietary questionnaire increased the proportion of non-adherent patients to 34%. Adding stool GIP detection increased this proportion to 51% and 46% when combined with serology or the dietary questionnaire, respectively. Overall, 23/41 patients (56%) showed evidence of gluten exposure when positivity in at least one of the three methods was considered. Conclusions: A high rate of recent gluten exposure was detected in children with CD on a long-term GFD. Stool GIP detection may provide complementary information to conventional methods for monitoring GFD adherence and may help identify patients requiring further dietary assessment or intervention.