Moving Beyond Isothiocyanates: A Look at the Stability of Conjugation Links Toward Radiolysis in 89Zr-Labeled Immunoconjugates.

Zirconium-89 is the most widely used radioisotope for immunoPET because its physical half-life (78.2 h) suits the one of antibodies. Desferrioxamine B (DFO) is the standard chelator for the complexation of zirconium(IV), and its bifunctional version, containing a phenylisothiocyanate function, is the most commonly used for the conjugation of DFO to proteins. However, preliminary results have shown that the thiourea link obtained from the conjugation of isothiocyanate and lysines is sensitive to the ionizing radiation generated by the radioisotope, leading to the rupture of the link and the release of the chelator/radiometal complex. This radiolysis phenomenon could produce nonspecific signal and prevent the detection of bone metastasis, as free zirconium accumulates into the bones. The aim of this work was to study the stability of a selection of conjugation linkers in 89Zr-labeled immunoconjugates. We have synthesized several DFO-based bifunctional chelators appended with an isothiocyanate moiety, a bicyclononyne, or a squaramate ester. Two antibodies (trastuzumab and rituximab) were conjugated and radiolabeled with zirconium-89. The effect of increasing activities of zirconium-89 on the integrity of the bioconjugate bearing thiourea links was evaluated as well as the impact of the presence of a radioprotectant. The stability of the radiolabeled antibodies was studied over 7 days in PBS and human plasma. Radioconjugates' integrity was evaluated using iTLC and size-exclusion chromatography. This study shows that the nature of the linker between the chelator and biomolecule can have a strong impact on the stability of the 89Zr-labeled conjugates, as well as on the aggregation of the conjugates.

Evaluation of sensory acceptance, purchase intention and color parameters of potentially probiotic mead with Saccharomyces boulardii.

Mead is a fermented alcoholic beverage produced by yeast action on a diluted solution of honey. In this study, for the first time, sensory acceptance, purchase intention and color parameters of potentially probiotic mead with Saccharomyces boulardii were evaluated. The mead with S. boulardii presented yeast counts higher than 106 CFU/mL, being considered potentially probiotic, and tended to be yellow in color. About 160 tasters participated in the sensory evaluation, and 69.38% knew mead, but only 35.62% had tried the beverage. In terms of acceptance, the mead were within the acceptable range (above 5), and F2 (with initial soluble solids of 30° Brix and S. boulardii concentration of 0.030 g/L) was the most accepted, with an overall average of 7.63 ± 1.42 on the nine-point hedonic scale. In addition, F2 presented the highest purchase intention. In conclusion, the mead showed a tendency towards the color yellow and good sensory acceptance.

Prophylactic mesh does not prevent parastomal hernia in long-term: Meta-analysis and trial sequential analysis.

BACKGROUND: Previous randomized clinical trials, systematic reviews, and meta-analyses evaluating parastomal hernia prevention with mesh placement during end colostomy formation have reported contradictory results. This review aimed to assess the efficacy of this strategy in long-term follow-up according to the latest available data. METHODS: Medline, EMBASE, Cochrane Library, Web of Science, and Google Scholar were searched. Randomized clinical trials were included if they compared mesh with no mesh during initial end colostomy creation in adult patients to prevent parastomal hernia with a follow-up longer than 2 years. A meta-analysis was performed to evaluate parastomal hernia incidence (primary outcome), parastomal hernia repair rate, and mortality. Subgroup analysis included surgical approach and mesh position, and trial sequential analysis was performed. RESULTS: Eight randomized clinical trials involving 537 patients met the inclusion criteria. Based on long-term follow-up, the incidence of parastomal hernia was not reduced when a prophylactic mesh was placed (relative risk = 0.68 [95% confidence interval:0.46-1.02]; I2 = 81%, P =.06). The parastomal hernia repair rate was low; however, no difference was found between the groups (relative risk = 0.90 [95% confidence interval:0.51-1.56]; I2 = 0%; P = .70), and no difference was detected between the groups when mortality was assessed (relative risk = 1.03 [95% confidence interval: 0.77-1.39]; I2 = 21%; P = .83). Subgroup analyses did not show differences according to the surgical approach or mesh position used. Regarding trial sequential analysis, an optimal information size was not achieved. CONCLUSION: Prophylactic mesh placement during end colostomy formation does not prevent parastomal hernia in the long term. The parastomal hernia repair rate and mortality rate did not vary between the included groups. Heterogeneity among the included randomized clinical trials might restrict the reliability of the results.

Synthesis and Preclinical Fluorescence Imaging of Dually Functionalized Antibody Conjugates Targeting Endothelin Receptor-Positive Tumors.

For the past two decades, the emerging role of the endothelin (ET) axis in cancer has been extensively investigated, and its involvement in several mechanisms described as "hallmarks of cancer" has clearly highlighted its potential as a therapeutic target. Despite the growing interest in finding effective anticancer drugs, no breakthrough treatment has successfully made its way to the market. Recently, our team reported the development of a new immuno-positron emission tomography probe targeting the ET A receptor (ETA, one of the ET receptors) that allows the successful detection of ETA+ glioblastoma, paving the way for the elaboration of novel antibody-based strategies. In this study, we describe the synthesis of two PET/NIRF (positron emission tomography/near-infrared fluorescence) dually functionalized imaging agents, directed against ETA or ETB, that could be used to detect ET+ tumors and select patients that will be eligible for fluorescence-guided surgery. Both imaging modalities were brought together using a highly versatile tetrazine platform bearing the IRDye800CW fluorophore and desferrioxamine for 89Zr chelation. This so-called monomolecular multimodal imaging probe was then "clicked", via an inverse-electron-demand Diels-Alder reaction, to antibodies conjugated site-specifically with a trans-cyclooctene group. This approach has led to homogeneous and well-defined constructs that retained their high affinity and high specificity for their respective target, as shown by flow cytometry and NIRF in vivo imaging experiments in nude mice bearing CHO-ETA and CHO-ETB tumors. Ultimately, these bimodal immunoconjugates could be used to improve the outcomes of patients with ET+ tumors.

SPECT Imaging of Lysyl Oxidase-like 2 in a Model of Idiopathic Pulmonary Fibrosis.

Noninvasive imaging of idiopathic pulmonary fibrosis (IPF) remains a challenge. The aim of this study was to develop an antibody-based radiotracer targeting Lysyl Oxidase-like 2 (LOXL2), an enzyme involved in the fibrogenesis process, for SPECT/CT imaging of pulmonary fibrosis. The bifunctional chelator DOTAGA-PEG4-NH2 was chemoenzymatically conjugated to the murine antibody AB0023 using microbial transglutaminase, resulting in a degree of labeling (number of chelators per antibody) of 2.3. Biolayer interferometry confirmed that the binding affinity of DOTAGA-AB0023 to LOXL2 was preserved with a dissociation constant of 2.45 ± 0.04 nM. DOTAGA-AB0023 was then labeled with 111In and in vivo experiments were carried out in a mice model of progressive pulmonary fibrosis induced by intratracheal administration of bleomycin. [111In]In-DOTAGA-AB0023 was injected in three groups of mice (control, fibrotic, and treated with nintedanib). SPECT/CT images were recorded over 4 days p.i. and an ex vivo biodistribution study was performed by gamma counting. A significant accumulation of the tracer in the lungs of the fibrotic mice was observed at D18 post-bleomycin. Interestingly, the tracer uptake was found selectively upregulated in fibrotic lesions observed on CT scans. Images of mice that received the antifibrotic drug nintedanib from D8 up to D18 showed a decrease in [111In]In-DOTAGA-AB0023 lung uptake associated with a decrease in pulmonary fibrosis measured by CT scan. In conclusion, we report the first radioimmunotracer targeting the protein LOXL2 for nuclear imaging of IPF. The tracer showed promising results in a preclinical model of bleomycin-induced pulmonary fibrosis, with high lung uptake in fibrotic areas, and accounted for the antifibrotic activity of nintedanib.

Sphenoid sinuses' volume and area analysis of Brazilian individuals' CBCTs, related to sex, age, skin color, and nutritional status using DDS-Pro™ software.

The purpose of this study was to analyze the volume and area of sphenoid sinuses of Brazilian individuals' cone-beam computed tomography (CBCT) images using the beta version of the DDS-Pro™ 2.14.2_2022 software (DPP Systems, Czestochowa, Poland), to assess a potential correlation to sex, age, skin color, and nutritional status, and to evaluate differences between the right and left sides. Three-dimensional volume and area measurements were made with the software using CBCT images of 113 living Brazilian individuals of both sexes (67 females and 46 males). TEM, rTEM, and R were used to assess the reproducibility of inter- and intra-examiner measurements. The measurement means were estimated with 95% confidence intervals according to sex and age group. There were no significant differences between the left and right sides for both volume and area and between the sexes and black and white individuals. Volume and area were significantly higher in 18 years or older (p < 0.05) and in individuals with normal body mass index (BMI) (p < 0.05). The obtained results do not allow indicating the use of sphenoid sinuses volume and area measurements to estimate sexual dimorphism, and the same occurred for skin color. However, such measures can help to estimate age. Further studies are suggested with a larger sample, especially for the nutritional status variable.

ImmunoPET imaging-based pharmacokinetic profiles of an antibody and its Fab targeting endothelin A receptors on glioblastoma stem cells in a preclinical orthotopic model.

BACKGROUND: The resistance of glioblastoma stem cells (GSCs) to treatment is one of the causes of glioblastoma (GBM) recurrence. Endothelin A receptor (ETA) overexpression in GSCs constitutes an attractive biomarker for targeting this cell subpopulation, as illustrated by several clinical trials evaluating the therapeutic efficacy of endothelin receptor antagonists against GBM. In this context, we have designed an immunoPET radioligand combining the chimeric antibody targeting ETA, chimeric-Rendomab A63 (xiRA63), with 89Zr isotope and evaluated the abilities of xiRA63 and its Fab (ThioFab-xiRA63) to detect ETA+ tumors in a mouse model xenografted orthotopically with patient-derived Gli7 GSCs. RESULTS: Radioligands were intravenously injected and imaged over time by µPET-CT imaging. Tissue biodistribution and pharmacokinetic parameters were analyzed, highlighting the ability of [89Zr]Zr-xiRA63 to pass across the brain tumor barrier and achieve better tumor uptake than [89Zr]Zr-ThioFab-xiRA63. CONCLUSIONS: This study shows the high potential of [89Zr]Zr-xiRA63 in specifically targeting ETA+ tumors, thus raising the possibility of detecting and treating ETA+ GSCs, which could improve the management of GBM patients.

Modular One-Pot Strategy for the Synthesis of Heterobivalent Tracers.

Bivalent ligands, i.e., molecules having two ligands covalently connected by a linker, have been gathering attention since the first description of their pharmacological potential in the early 80s. However, their synthesis, particularly of labeled heterobivalent ligands, can still be cumbersome and time-consuming. We herein report a straightforward procedure for the modular synthesis of labeled heterobivalent ligands (HBLs) using dual reactive 3,6-dichloro-1,2,4,5-tetrazine as a starting material and suitable partners for sequential SNAr and inverse electron-demand Diels-Alder (IEDDA) reactions. This assembly method conducted in a stepwise or in a sequential one-pot manner provides quick access to multiple HBLs. A conjugate combining ligands toward the prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPR) was radiolabeled, and its biological activity was assessed in vitro and in vivo (receptor binding affinity, biodistribution, imaging) as an illustration that the assembly methodology preserves the tumor targeting properties of the ligands.

Growing conditions of Saccharomyces boulardii for the development of potentially probiotic mead: Fermentation kinetics, viable cell counts and bioactive compounds.

Mead is an alcoholic beverage produced by the fermentation of a diluted honey solution by the action of yeast. Recently, research has shown the potential of S. boulardii for brewing beer and in the development of probiotic alcoholic beverages and, to date, no research has examined for mead production. The aim of this study was to evaluate the growth conditions of S. boulardii for the development of potentially probiotic mead. The findings show that initial wort soluble solids conditions of 30°Brix and initial concentration of 0.030 g/L of S. boulardii obtain potentially probiotic mead with viable yeast cells of 6.53 Log10 CFU/mL, alcohol content of 5.05%, and has the presence of total phenolics (17.72 mg GAE/100 mL) and natural antioxidants (62.79 and 1.37 µmol TE/100 mL for ABTS and FRAP methods, respectively). In conclusion, S. boulardii has a potential for the development of probiotic mead.

Accuracy of partially and fully guided surgical techniques for immediate implant placement: An in vitro assessment.

STATEMENT OF PROBLEM: Optimal implant positioning is essential to achieving predictable results. Computer-guided surgery has been reported to be an accurate technique for implant placement in healed sites, but the accuracy of guided techniques for immediate implant placement into fresh sockets is still unclear. PURPOSE: The purpose of this experimental randomized split-mouth study in pig jaws was to determine the accuracy of partially and fully guided surgical techniques for immediate implant placement into fresh sockets and to compare 2 different methods of implant position deviations analysis. MATERIAL AND METHODS: Twenty implants were installed in 10 pig jaws using 2 different techniques: partially guided (n=10) and fully guided (n=10). Cone beam computed tomography and digital scanning were performed before and after the surgical procedure to plan the virtual implant position and fabricate the surgical guide, as well as to determine implant position deviations. Two methods were used to evaluate implant deviations: tomographic and digital scanning. The Shapiro-Wilk test of normality was used. Deviation comparisons were carried out by using paired t tests (α=.05), and intraclass correlation coefficient (ICC) was computed to assess the agreement between the 2 methods of implant deviation analysis. RESULTS: In the tomographic analysis, the partially guided technique resulted in significantly higher global apical and lateral coronal deviations (2.25 ±0.59 mm; 0.96 ±0.55 mm) than fully guided (1.52 ±0.89 mm; 0.75 ±0.52 mm) (P<.01 and P<.05, respectively). The analysis performed using digital scanning showed significantly higher angular, global apical, and lateral apical deviations in the partially guided (6 ±3.28 degrees; 2.49 ±1.03 mm; 2.16 ±1.07 mm) technique than in the fully guided (3.32 ±1.84 degrees; 1.5 ±0.58 mm; 0.98 ±0.67 mm) (P<.05). An ICC of 0.522 between the 2 methods of implant deviation analysis was obtained. CONCLUSIONS: The partially guided technique was less accurate than the fully guided technique for immediate implant placement into fresh sockets. A moderate concordance was observed between cone beam computed tomography and digital scanning analyses, suggesting that more studies are required to validate and to define the most reliable method of measuring implant deviation.

Recent advances in the application of xylanases in the food industry and production by actinobacteria: A review.

The microbial production of enzymes has been gaining prominence in the industry, because, in addition to presenting specificity and acting in mild reaction conditions, they can also be considered eco-friendly. An example with growing importance for the food industry is xylanases, which are prominent in beverage processing, bakery products and the production of emerging prebiotics. Microorganisms of the phylum Actinobacteria are promising sources for the production of these enzymes, however few studies in the literature report investigations on the production of xylanases by actinobacteria. This review brings together important information on the production of xylanases by actinobacteria and recent advances in the use of the enzyme in the food industry.

Novel time-domain NMR-based traits for rapid, label-free Olive oils profiling.

Olive oil is one of the oldest and essential edible oils in the market. The classification of olive oils (e.g. extra virgin, virgin, refined) is often influenced by factors ranging from its complex inherent physiochemical properties (e.g. fatty acid profiles) to the undisclosed manufacturing processes. Therefore, olive oils have been the target of adulteration due to its profitable margin. In this work, we demonstrate that multi-parametric time-domain NMR relaxometry can be used to rapidly (in minutes) identify and classify olive oils in label-free and non-destructive manner. The subtle differences in molecular microenvironment of the olive oils induce substantial changes in the relaxation mechanism in the time-domain NMR regime. We demonstrated that the proposed NMR-relaxation based detection (AUC = 0.95) is far more sensitive and specific than the current gold-standards in the field i.e. near-infrared spectroscopy (AUC = 0.84) and Ultraviolet-visible spectroscopy (AUC = 0.73), respectively. We further show that, albeit the inherent complexity of olive plant natural phenotypic variations, the proposed NMR-relaxation based traits may be a viable mean (AUC = 0.71) in tracing the regions of origin for olive trees, in agreement with their geographical orientation.

Underlying IPEX syndrome in a patient with idiopathic juvenile arthritis and vitiligo.

BACKGROUND: IPEX syndrome is an X-linked inborn error of immunity clinically characterized by the triad of: enteropathy, polyendocrinopathy and eczema. However many other clinical presentations lacking the triad above described have been reported what underpin the need of careful clinical suspicion, immunological evaluation and genetic sequencing. CASE PRESENTATION: Here we report a case of a Brazilian boy with severe eczema as the first and only presentation requiring cyclosporin therapy. Progressive and cumulative symptoms of arthritis and enteropathy lead to the suspicion of an inborn error of immunity. Peripheral FOXP3 expression was normal (CD127-/CD4+/CD25+/FOXP3+-396 cells-63%) and a pathogenic mutation in FOXP3 gene (c.1150G>A; p.Ala384Thr), confirmed the diagnosis of IPEX syndrome. CONCLUSIONS: IPEX syndrome should be suspected in patients presenting with severe eczema associated or not with other autoimmune/hyper inflammatory diseases in life. Our study also reinforces that FOXP3 expression by flowcytometry seems not to be a good screening method, and genetic sequencing is mandatory even in those with high suspicion and normal peripheral FOXP3 expression.

The use of 3D ceramic block graft compared with autogenous block graft for rehabilitation of the atrophic maxilla: a randomized controlled clinical trial.

BACKGROUND: Dental implant placement may require a bone graft for vertical and horizontal alveolar ridge augmentation. Due to its osteoconduction, osteoinductive, and osteogenesis, autogenous bone graft characteristics are considered the standard gold treatment. However, autografts can promote postoperative morbidity and implicate difficulties concerning the graft adaptation to the recipient's bone since it can eventually avoid gaps. To overcome these issues, this trial will compare the performance of Plenum® Oss 3Dß fit, an alloplastic graft, and a 3D-printed patient-specific graft based on ß-tricalcium phosphate to the autograft procedure. METHODS: This is a split-mouth randomized clinical study designed to evaluate the performance of personalized (patient-specific) bioceramic bone grafts (Plenum® Oss 3Dß fit) for bone augmentation of the atrophic anterior maxilla in comparison to the autogenous bone graft. We hypothesize that the gain and maintenance of the grafted area volume and the quality of the newly formed bone tissue after eight months postoperative with the synthetic patient-specific graft will be superior to the autogenous bone graft. To assess the quantity and the quality of bone neoformation, volumetric and histological analyses will be performed. DISCUSSION: The fabrication of medical devices by additive manufacturing presents advantages over conventional manufacturing processes, mostly related to the precision of geometry and anatomy. Additionally, the osteoconductive proprieties of ß-tricalcium phosphate enable this synthetic bone substitute as an alternative solution over autogenous graft for bone defect reconstruction. Thus, patient-specific bone grafts can potentially improve patient satisfaction, reducing the need for autogenous bone grafts, consequently avoiding implications related to this type of treatment, such as patient morbidity. TRIAL REGISTRATION: This study is registered in REBEC (Registro Brasileiro de Ensaios Clínicos): RBR-76wmm3q; UTN: U1111-1272-7773. Registration date: 14 September 2021.

The SRPK inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl) isonicotinamide (SRPIN340) increases the immune response against metastatic melanoma in mice.

Cancers have a strong relationship with immune cells in their microenvironment, which significantly influences tumor proliferation and progression. Thus, pharmacological strategies that stimulate the immune system to combat tumor cells are promising for better therapeutic efficacy. Deregulated expression of the splicing regulatory serine arginine protein kinases (mostly SRPK1 and SRPK2) has been found in different cancer types, leading to the expression of isoforms related to tumor growth and metastasis. The microenvironment of melanoma exhibits a strong presence of immune cells, which significantly influences tumor progression, and around 50% of cutaneous melanoma patients benefit from targeted immunotherapy. Here, we analyzed human malignant melanoma single-cell gene expression data and observed that SRPK1/2 overexpression correlates with immune system pathway alterations. In further analysis, we observed an increased presence of immune cells in biopsies from mice bearing metastatic melanoma treated with SRPIN340, a well-known SRPK1/2 pharmacological inhibitor. Local treatments increased the expression of proinflammatory cytokines at the tumor lesions and the activity of the spleen, accompanied by reduced pulmonary metastasis foci, edema formation, and alveolar congestion. In in vitro assays, SRPIN340 also potentiated immunological susceptibility, by increasing the expression of the antigen presenting MHCI and MHCII molecules and by increasing the ability of B16F10 cells to attract splenic cells in transwell assays. Taken together, these results reveal that the antimetastatic effect of SRPIN340 can also involve an increased immune response, which suggests additional functional clues for SRPKs in tumor biology.

Network analysis of pig movements in Ecuador: Strengthening surveillance of classical swine fever.

The analysis of domestic pig movements has become useful to understand the disease spread patterns and epidemiology, which facilitates the development of more effective animal diseases control strategies. The aim of this work was to analyse the static and spatial characteristics of the pig network, to identify its trading communities and to study the contribution of the network to the transmission of classical swine fever. In this regard, we used the pig movement records from the National Veterinary Service of Ecuador (2017-2019), using social network analysis and spatial analysis to construct a network with registered premises as nodes and their movements as edges. Furthermore, we also created a network of parishes as its nodes by aggregating their premises movements as edges. The annual network metrics showed an average diameter of 20.33, a number of neighbours of 2.61, a shortest path length of 4.39 and a clustering coefficient of 0.38 (small-world structure). The most frequent movements were to or from markets (55%). Backyard producers made up 89% of the network premises, and the top 2% of parishes (highest degree) contributed to 50% of the movements. The highest frequencies of movements between parishes were in the centre of the country, while the highest frequency of movements to abattoirs was in the south-west. Finally, the pattern of classical swine fever (CSF) disease outbreaks within the Ecuador network was likely the result of network transmission processes. In conclusion, our results represented the first exploratory analysis of domestic pig movements at premise and parish levels. The surveillance system could consider these results to improve its procedures and update the disease control and management policy, and allow the implementation of targeted or risk-based surveillance.

Three-dimensional analysis of the maxillary sinus according to sex, age, skin color, and nutritional status: A study with live Brazilian subjects using cone-beam computed tomography.

OBJECTIVE: To perform three-dimensional measurements (volume and area) of the maxillary sinus, from cone-beam computed tomography (CBCT) images, and to assess potential differences between the left and right sides and a correlation of the measurements to sex, age, skin color, and nutritional status. DESIGN: CBCT images of 161 living Brazilian subjects of both sexes (89 women and 72 men) were used, and three-dimensional measurements of volume and area were made with the beta version of the DDS-Pro™ 2.14.2_2022 software (DPP Systems, Czestochowa, Poland). The inter- and intra-examiner reproducibility of measurements was evaluated with TEM, rTEM, and R. RESULTS: Both maxillary sinus volume and area did not show significant differences between the left and right sides and between the sexes. Volume and area were significantly lower in the age group from 6 to 11 years than in the other two groups (p < 0.05). The measurements obtained for maxillary sinus volume and area were significantly higher in white individuals (p < 0.05), but they did not show significant differences (p > 0.05) regarding nutritional status (considering the body mass index - BMI). CONCLUSION: There were no statistically significant differences between the sexes, which does not allow recommending the use of maxillary sinus volume and area measurements to analyze sexual dimorphism, and the same occurs for BMI. However, such measures can help to estimate the age and skin color of individuals.

Site-Specific, Platform-Based Conjugation Strategy for the Synthesis of Dual-Labeled Immunoconjugates for Bimodal PET/NIRF Imaging of HER2-Positive Tumors.

Because positron emission tomography (PET) and optical imaging are very complementary, the combination of these two imaging modalities is very enticing in the oncology field. Such bimodal imaging generally relies on imaging agents bearing two different imaging reporters. In the bioconjugation field, this is mainly performed by successive random conjugations of the two reporters on the protein vector, but these random conjugations can alter the vector properties. In this study, we aimed at abrogating the heterogeneity of the bimodal imaging immunoconjugate and mitigating the impact of multiple random conjugations. A trivalent platform bearing a DFO chelator for 89Zr labeling, a NIR fluorophore, IRDye800CW, and a bioconjugation handle was synthesized. This bimodal probe was site-specifically grafted to trastuzumab via glycan engineering. This new bimodal immunoconjugate was then investigated in terms of radiochemistry, in vitro and in vivo, and compared to the clinically relevant random equivalent. In vitro and in vivo, our strategy provides several improvements over the current clinical standard. The combination of site-specific conjugation with the monomolecular platform reduced the heterogeneity of the final immunoconjugate, improved the resistance of the fluorophore toward radiobleaching, and reduced the nonspecific uptake in the spleen and liver compared to the standard random immunoconjugate. To conclude, the strategy developed is very promising for the synthesis of better defined dual-labeled immunoconjugates, although there is still room for improvement. Importantly, this conjugation strategy is highly modular and could be used for the synthesis of a wide range of dual-labeled immunoconjugates.

PLGA-Based Composites for Various Biomedical Applications.

Polymeric materials have been extensively explored in the field of nanomedicine; within them, poly lactic-co-glycolic acid (PLGA) holds a prominent position in micro- and nanotechnology due to its biocompatibility and controllable biodegradability. In this review we focus on the combination of PLGA with different inorganic nanomaterials in the form of nanocomposites to overcome the polymer's limitations and extend its field of applications. We discuss their physicochemical properties and a variety of well-established synthesis methods for the preparation of different PLGA-based materials. Recent progress in the design and biomedical applications of PLGA-based materials are thoroughly discussed to provide a framework for future research.