This study developed a nanoscaled system combining chemotherapeutic (Temozolomide, TMZ) and radionuclide (177Lu) for targeted glioblastoma (GBM) treatment. Bioorthogonal click chemistry was utilized to produce a selective delivery platform, and the impacts of nanomedicine structure on the efficiency of bioorthogonal reactions were explored in vivo. This was achieved by developing two parallel polymers with trans-cyclooctene (tCO) in positions differing in terms of the accessibility to the tetrazine-containing moiety. Both in vitro assessment of reaction kinetics and the in vivo distribution behavior demonstrated that tCO conjugated at the chain end of the polymer (PTtCOext) instead of those within chains (PTtCOint) exhibited better accessibility to the tetrazine-modified material ([177Lu]Lu-DPT). This then led to a more efficient click reaction in vivo and higher 177Lu accumulation in the tumor. This study provides key information on design considerations for optimal positioning of bioorthogonal reactive species in nanomedicine and a potential treatment approach for GBM.

Au(I) N-heterocyclic carbene (NHC) complexes have shown promising cytotoxicity against cancer cells, yet improving their selectivity remains a key challenge. In this study, a modular strategy to enhance tumor targeting by post-functionalizing an Au(I) bis-aNHCtrz complex (trz = 1,2,3-triazole-5-ylidene) with oestradiol via copper-catalyzed click chemistry is introduced. The resulting conjugate shows high cytotoxicity in the nanomolar range and markedly increased accumulation in ERα-positive breast cancer cells compared to its non-functionalized analogue. This work demonstrates the potential of hormone-based vectors to guide gold complexes selectively to hormone receptor-positive cancer cells.

Mitochondrial Transcription: A click-chemistry derived detection methodology forgoing the use of radiation in in vitro analyses.

Alkyne modification of DNA cross-linking antitumor agent SJG-136 to monitor induced lesions in cells by click chemistry.

Synthesis and characterization of triple acid stationary phases for cation exchange chromatography using click chemistry and atom transfer radical polymerization.

Stable isotope-labeled paper spray mass spectrometry enables high-sensitivity profiling of protease activity.

Rationale: Proliferative retinopathies are the leading causes of blindness worldwide. Current treatment paradigms rely heavily on intravitreal injections of anti-vascular endothelial growth factor A (anti-VEGFA) agents, which, despite their efficacy, are associated with ocular complications and patient discomfort. To address these challenges, we have developed a novel mixed-layered trehalose-functionalized dendrimer (Tre-D) conjugated with Axitinib, a multi-receptor tyrosine kinase inhibitor, (Tre-D-Axitinib) for systemic delivery to aberrant neovascular tufts in retina.Methods: Tre-D is synthesized through a scalable and convenient synthetic methodology using click chemistry. The in vitro cytocompatibility, uptake and angiogenesis assays are carried out in Human Retinal Microvascular Endothelial Cells (HRMECs), Human umbilical vein endothelial cells (HUVECs) and macrophages (RAW-Blue). The in vivo uptake and efficacy of Tre-D-Axitinib are evaluated in a mouse model of oxygen induced retinopathy (OIR) via intraperitoneal (IP) administration of the treatment.Results: The Tre-D demonstrates inherent targeting to neovascular tufts in an OIR mouse model. Tre-D-Axitinib leads to increased vaso-obliteration in the ischemic retina. The IP administration of Tre-D-Axitinib effectively reduces pathological retinal neovascularization, tuft formation, and vessel anastomoses while showing minimal off-target effects and rapid renal clearance. Mechanistic studies reveal that Tre-D-Axitinib inhibits VEGFA-induced proliferation, migration, and angiogenesis in human retinal endothelial cells.Conclusions: To date, there are no organic nanoparticles that localize selectively in aberrant neovascular tufts at the site of pathology in retina when systemically administered. By eliminating the need for invasive intravitreal injections and addressing systemic toxicities, Tre-D-Axitinib introduces a novel systemic nanotherapeutic strategy with broad implications for treating ischemic retinopathies.

Sialic acid mimetics (SAMs) are chemically modified derivatives of sialic acids that can act as metabolic inhibitors or as sugar donors for sialyltransferases. This makes SAMs highly useful research tools to study and manipulate the biosynthesis of sialic acid-carrying glycans (sialoglycans). Moreover, SAMs that inhibit aberrant sialylation in cancer cells are emerging as potential therapeutics. Despite the wide use of SAMs, many aspects regarding their cellular uptake and metabolic fate are unknown. Here, we investigated the metabolic fate of an inhibitory SAM (P-SiaFNEtoc) and an incorporative SAM (P-SiaNPoc) in various mammalian cell lines. Using kinetic experiments and read-outs based on sialic acid-binding lectins, click chemistry, and nucleotide sugar analysis, we monitored the key steps of cellular SAM utilization. We found differences in the metabolism of SAMs that determine their potency in different mammalian cell lines. By identifying a murine macrophage cell line that is insensitive to SAMs, we have identified esterase activity as a bottleneck for the cellular utilization of SAMs. This study contributes to the understanding of the mechanisms underlying SAMs utilization in mammalian cell lines and provide relevant considerations for the future chemical design of SAMs and their application in mammalian systems.

Superhydrophilic COFs synthetized through click chemistry and the application in interlayered thin-film composite membranes for nanofiltration

Multimodal cation exchange-type tyrosine-based chiral stationary phases: Synthesis and applications in high-performance liquid chromatography.

Rationale: Glycosylation of drug delivery vehicles enables selective tumor microenvironment (TME) targeting but is limited by the lack of precise glycan control and unbiased evaluation of in situ targeting. We developed a clickable albumin nanoplatform engineered by distinct glycosylation for selective in vivo cell targeting (CAN-DGIT) with a defined number of sugar moieties and integrated spatial transcriptomics (ST) to map nanoparticle-TME interactions. Methods: Albumin was functionalized with azadibenzocyclooctyne (ADIBO) at a controlled degree of functionalization (DOF), confirmed by MALDI-TOF and UV-vis spectroscopy, followed by conjugation of azide-functionalized mannose, galactose, or glucose via click chemistry. Nanoparticles were labeled with 64Cu or fluorescent dyes for PET imaging and ex vivo analysis in healthy and 4T1 tumor-bearing mice. ST based algorithms, spatial gene-image integration (SPADE), cell-type deconvolution (CellDART), and image-based molecular signature analysis (IAMSAM), were used to define TME clusters, associated cell populations, and glycan receptor gene signatures. Clodronate-loaded glycosylated albumins were tested for tumor-associated macrophage (TAM) depletion. Results: Glycosylation type of CAN-DGIT dictated pharmacokinetics and targeting. Mannosylated albumin (Man-Alb) showed rapid hepatic retention via mannose receptors on Kupffer cells and TAMs; galactosylated albumin (Gal-Alb) exhibited rapid hepatobiliary clearance with the highest tumor-to-liver ratio; glucosylated albumin at the C6 position (Glc(6)-Alb) progressively accumulated in tumors, correlating with glucose transporter 1 (GLUT1)-expressing cancer cells. ST confirmed Man-Alb enrichment in extracellular matrix (ECM)/TAM-rich clusters (mannose receptor C-type 1, Mrc1-high) and Gal-/Glc-Alb uptake in glycolytic/hypoxic tumor clusters (Slc2a1-high). Man-Alb-clodronate achieved potent CD206+ TAM depletion without altering drug release kinetics. Conclusions: Precisely tuned glycosylation enables programmable biodistribution and cell-type targeting of albumin nanoparticles in the TME. Integrating PET with ST provides a robust framework for mechanistic mapping of nanomedicine uptake. The CAN-DGIT platform offers a versatile strategy for developing targeted theranostic agents with immunomodulatory potential.

Synthesis, antimicrobial activity and in-silico studies of (1-(1-arylethyl)-1H-1,2,3-triazolyl-2-phenylquinoline-4-carboxylate derivatives with click chemistry.

Chemical residues in food pose a global health challenge, which necessitates sensitive and reliable detection methods. Current techniques (e.g., chromatography and immunoassays) remain limited by operational complexity, insufficient sensitivity, and poor adaptability for on-site use. Click chemistry has emerged as a novel solution, offering rapid, specific, and ultrasensitive detection of food chemical residues, such as pesticides, antibiotics, and hormones-contaminants that pose significant health threats through chronic exposure. This review outlines the principles and classifications of click reactions, emphasizing their selectivity, mild reaction conditions, and modular design. Integrating biosensors enhances molecular recognition and signal amplification, enabling on-site screening in complex food matrices. We critically evaluate recent click chemistry-based sensors, detailing their design strategies (e.g., probe functionalization and nanomaterial engineering) and optimization via advanced transduction mechanisms. Key challenges-including matrix interference, reagent stability, and cost-are addressed through molecular imprinting, microfluidic miniaturization, and AI-driven system refinement. Future advancements will focus on integrating green chemistry to reduce environmental impact, developing multiplexed platforms for high-throughput detection, and expanding applications to emerging contaminants such as microplastics and biotoxins. These innovations promise to redefine food safety standards with scalable, next-generation analytical tools.

The Tn antigen is a key tumor-associated antigen and a promising cancer biomarker. However, its low abundance poses great challenges for sensitive detection. We developed a novel approach that integrates B3GNT6-mediated Tn-specific labelling, click chemistry, and chemiluminescence detection to enable quantitative and sensitive analysis of Tn antigen.

Chemical reactions compatible with multiple functionalities are essential for rapid, programmable, and automatable synthesis of functional molecules. However, achieving such reactivity poses significant challenges. Here, we developed a novel multi-orthogonal C(sp2)–Se bond formation reaction between benzoselenazolones and boronic acids via Ag(i)-catalyzed selective selenium(ii)–nitrogen exchange. This chemistry is compatible with diverse functionalities, enabling sequential and programmable synthesis. Moreover, it features modular, high-yielding (485 examples, with yields or conversions exceeding 70% in 95% of cases), and switchable reaction systems under mild conditions. Its practical utility was exemplified through late-stage functionalization of natural products, peptide modification and ligation, diversified synthesis, sequential click chemistry, protecting group-free syntheses of sequence-defined oligo selenides (nonamers), on-plate nanomole-scale parallel synthesis (200 nmol, 412 selenides), and DNA-encoded library (DEL) synthesis (10 nmol, 92 examples). Notably, a target-based screening identified SA-16 as a potent CAXII inhibitor with an IC50 value of 72 nM. Furthermore, a machine learning-based model (SeNEx-ML) was established for reaction yield prediction, achieving 80% accuracy in binary classification and 70% balanced accuracy in ternary classification. These results demonstrated that this chemistry serves as a powerful tool to bridge the selenium chemical space with the existing chemical world, offering transformative potential across multidisciplinary fields.

EGFR-targeted extracellular vesicles loaded with doxorubicin for enhanced chemotherapy in non-small cell lung cancer via bioorthogonal click chemistry.

Engineered mesenchymal stem cells for targeted delivery of H2S to suppress cGAS-STING inflammation and enhance cardioprotection in myocardial ischemia-reperfusion.

Structure-oriented molecular extension strategies unlock C-glycoside insecticides targeting OfChtII and OfHex1.

A Calix[4]arene-based wettability interface sensor for rapid ATP detection.

A single-molecule biosensor based on multiple fluorophore nucleic acid probe and STORM imaging for detection of Hantaan virus.