Injectable Regenerated Silk Fibroin Micro/Nanosphere with Enhanced Permeability and Stability for Osteoarthritis Therapy.

In the therapy of early-stage osteoarthritis, to accomplish full infiltration of subchondral bone and cartilage, and to target osteoclast and chondrocyte simultaneously remain challenges in biomaterials design. Herein, a novel hierarchical drug delivery system is introduced, with micrometer-scale outer layer spheres composed of regenerated silk fibroin, characterized by connected porous structure through the n-butanol and regenerated silk fibroin combined emulsion route and freezing method. The design effectively resists clearance from the joint cavity, ensuring stable delivery and prolonged residence time within the joint space. Additionally, the system incorporates phenylboronic acid-enriched silk fibroin nanoparticles, stabilized through chemical cross-linking, which encapsulate isoliquiritin derived from Glycyrrhiza uralensis. These nanoparticles facilitate complete penetration of the cartilage extracellular matrix, exhibit pH-responsive behavior, neutralize reactive oxygen species, and enable controlled drug release, thereby enhancing therapeutic efficacy. The in vitro and in vivo experiments both demonstrate that the composite micro/nanospheres not only inhibit osteoclastogenesis with bone loss in subchondral bone and osteophyte formation, but also mitigate chondrocytes apoptosis, reduce oxidative stress associated with cartilage degeneration, and ameliorate neuropathic hyperalgesia, with the underlying mechanisms being elucidated. The study indicates that such an injectable strategy combining organic biomaterials with Chinese medicine holds substantial promise for the treatment of early osteoarthritis.

Phenylboronic acid interacts with pectic rhamnogalacturonan-II and displays anti-auxinic effects during Arabidopsis thaliana root growth and development.

Boron dimerizes RG-II in the plant cell wall and is crucial for plant cell elongation. However, studying RG-II dimerization in plants is challenging because of the severe phenotypes or lethality of RG-II mutants. Boron deprivation abrogates both RG-II dimerization and plant growth, but whether or how these phenotypes are functionally linked has remained unclear. Boric acid analogues can serve as experimental tools to interfere with RG-II cross-linking. Here, we investigated RG-II dimerization and developmental phenotypes in Arabidopsis thaliana seedlings treated with a boric acid analogue, phenylboronic acid (PBA), to test whether the observed developmental phenotypes are attributable to alteration of RG-II dimerization or to other putative functions of boron in plants. We found that PBA treatment altered root development in seedlings while RG-II dimerization and distribution were not affected. Surprisingly, under low boron conditions, PBA treatment i) had no effect on root size but still prevented lateral root development and ii) restored RG-II dimerization. PBA treatment also disrupted auxin levels, potentially explaining the absence of lateral roots in seedlings treated with this analogue. We conclude that PBA interacts both with RG-II and other cellular targets such as auxin signaling components, and that the phenotypes caused by PBA arise from interference with multiple functions of boron.

Amonafide-based H2O2-responsive theranostic prodrugs: Exploring the correlation between H2O2 level and anticancer efficacy.

Leveraging the elevated hydrogen peroxide (H2O2) levels in cancer cells, H2O2-activated prodrugs have emerged as promising candidates for anticancer therapy. Notably, the efficacy of these prodrugs is influenced by the varying H2O2 levels across different cancer cell types. In this context, we have developed a novel H2O2-activated prodrug, PBE-AMF, which incorporates a phenylboronic ester (PBE) motif. Upon H2O2 exposure, PBE-AMF liberates the fluorescent and cytotoxic molecule amonafide (AMF), functioning as a theranostic agent. Our studies with PBE-AMF have demonstrated a positive correlation between intracellular H2O2 concentration and anticancer activity. The breast cancer cell line MDA-MB-231, characterized by high H2O2 content, showed the greatest susceptibility to this prodrug. Subsequently, we replaced the PBE structure with phenylboronic acid (PBA) to obtain the prodrug PBA-AMF, which exhibited enhanced stability, aqueous solubility, and tumor cell selectivity. This selectivity is attributed to its affinity for sialic acid, which is overexpressed on the surfaces of cancer cells. In vitro assays confirmed that PBA-AMF potently and selectively inhibited the proliferation of MDA-MB-231 cells, while sparing non-cancerous MCF-10A cells. Mechanistic investigations indicated that PBA-AMF impedes tumor proliferation by inhibiting DNA synthesis, reducing ATP levels, inducing apoptosis, and arresting the cell cycle. Our work broadens the range of small molecule H2O2-activated anticancer theranostic prodrugs, which are currently limited in number. We anticipate that the applications of PBA-AMF will extend to a wider spectrum of tumors and other diseases associated with increased H2O2 levels, thereby offering new horizons in cancer diagnostics and treatment.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis.

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

Nanopore Discrimination of Nucleotide Sugars.

Nucleotide sugars, the glycosyl donors in the biosynthesis of carbohydrates, are critical ingredients in the growth and development of all living organisms. A variety of nucleotide sugars simultaneously exist in biological samples. They, however, have only minor structural differences, which make them extremely difficult to discriminate. In this work, a phenylboronic acid (PBA)-modified Mycobacterium smegmatis porin A (MspA) hetero-octamer was applied to sense nucleotide sugars. Five representative nucleotide sugars, including guanosine diphosphate mannose (GDP-Man), adenosine diphosphate glucose (ADP-Glc), uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), uridine diphosphate glucose (UDP-Glc), and uridine diphosphate glucoronic acid (UDP-GlcA), were successfully distinguished. A custom machine learning algorithm was also employed to automatically identify events, reporting a general accuracy of 99.4%. This sensing strategy provides a rapid, direct, and accurate method for identifying different nucleotide sugars. However, single-molecule identification of nucleotide sugars has never been previously reported, to the best of our knowledge.

Phenylboronic Acid-Functionalized Polyplexes Tailored to Oral CRISPR Delivery.

Effective delivery of the CRISPR-Cas9 components is crucial to realizing the therapeutic potential. Although many delivery approaches have been developed for this application, oral delivery has not been explored due to the degradative nature of the gastrointestinal tract. For this issue, we developed a series of novel phenylboronic acid (PBA)-functionalized chitosan-polyethylenimine (CS-PEI) polymers for oral CRISPR delivery. PBA functionalization equipped the polyplex with higher stability, smooth transport across the mucus, and efficient endosomal escape and cytosolic unpackaging in the cells. From a library of 12 PBA-functionalized CS-PEI polyplexes, we identified a formulation that showed the most effective penetration in the intestinal mucosa after oral gavage to mice. The optimized formulation performed feasible CRISPR-mediated downregulation of the target protein and reduction in the downstream cholesterol. As the first oral CRISPR carrier, this study suggests the potential of addressing the needs of both local and systemic editing in a patient-compliant manner.

Nanopore Signatures of Nucleoside Drugs.

Nucleoside drugs, which are analogues of natural nucleosides, have been widely applied in the clinical treatment of viral infections and cancers. The development of nucleoside drugs, repurposing of existing drugs, and combined use of multiple drug types have made the rapid sensing of nucleoside drugs urgently needed. Nanopores are emerging single-molecule sensors that have high resolution to resolve even minor structural differences between chemical compounds. Here, an engineered Mycobacterium smegmatis porin A hetero-octamer was used to perform general nucleoside drug analysis. Ten nucleoside drugs were simultaneously detected and fully discriminated. An accuracy of >99.9% was consequently reported. This sensing capacity was further demonstrated in direct nanopore analysis of ribavirin buccal tablets, confirming its sensing reliability against complex samples and environments. No sample separation is needed, however, significantly minimizing the complexity of the measurement. This technique may inspire nanopore applications in pharmaceutical production and pharmacokinetics measurements.

A Boron-Dependent Antibiotic Derived from a Calcium-Dependent Antibiotic.

The prevalence of drug-resistant bacterial pathogens foreshadows a healthcare crisis. Calcium-dependent antibiotics (CDAs) are promising candidates to combat infectious diseases as many of them show modes of action (MOA) orthogonal to widespread resistance mechanisms. The calcium dependence is nonetheless one of the hurdles toward realizing their full potential. Using laspartomycin C (LspC) as a model, we explored the possibility of reducing, or even eliminating, its calcium dependence. We report herein a synthetic LspC analogue (B1) whose activity no longer depends on calcium and is instead induced by phenylboronic acid (PBA). In LspC, Asp1 and Asp7 coordinate to calcium to anchor it in the active conformation; these residues are replaced by serine in B1 and condense with PBA to form a boronic ester with the same anchoring effect. Using thin-layer chromatography, MS, NMR, and complementation assays, we demonstrate that B1 inhibits bacterial growth via the same MOA as LspC, i.e., sequestering the cell wall biosynthetic intermediate undecaprenyl phosphate. B1 is as potent and effective as LspC against several Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Our success in converting a CDA to a boron-dependent antibiotic opens a new avenue in the design and functional control of drug molecules.

Sensitive Analysis of Recombinant Human Erythropoietin Glycopeptides by On-Line Phenylboronic Acid Solid-Phase Extraction Capillary Electrophoresis Mass Spectrometry.

In this study, several chromatographic sorbents: porous graphitic carbon (PGC), aminopropyl hydrophilic interaction (aminopropyl-HILIC), and phenylboronic acid (PBA) were assessed for the analysis of glycopeptides by on-line solid-phase extraction capillary electrophoresis mass spectrometry (SPE-CE-MS). As the PBA sorbent provided the most promising results, a PBA-SPE-CE-MS method was developed for the selective and sensitive preconcentration of glycopeptides from enzymatic digests of glycoproteins. Recombinant human erythropoietin (rhEPO) was selected as the model glycoprotein and subjected to enzymatic digestion with several proteases. The tryptic O126 and N83 glycopeptides from rhEPO were targeted to optimize the methodology. Under the optimized conditions, intraday precision, linearity, limits of detection (LODs), and microcartridge lifetime were evaluated, obtaining improved results compared to that from a previously reported TiO2-SPE-CE-MS method, especially for LODs of N-glycopeptides (up to 500 times lower than by CE-MS and up to 200 times lower than by TiO2-SPE-CE-MS). Moreover, rhEPO Glu-C digests were also analyzed by PBA-SPE-CE-MS to better characterize N24 and N38 glycopeptides. Finally, the established method was used to analyze two rhEPO products (EPOCIM and NeuroEPO plus), demonstrating its applicability in biopharmaceutical analysis. The sensitivity of the proposed PBA-SPE-CE-MS method improves the existing CE-MS methodologies for glycopeptide analysis and shows a great potential in glycoprotein analysis to deeply characterize protein glycosites even at low concentrations of the protein digest.

Sensitive and specific detection of saccharide species based on fluorescence: update from 2016.

Increasing evidence supports the critical role of saccharides in various pathophysiological steps of tumor progression, where they regulate tumor proliferation, invasion, hematogenic metastasis, and angiogenesis. The identification and recognition of these saccharides provide a solid foundation for the development of targeted drug preparations, which are however not fully understood due to their complex and similar structures. In order to achieve fluorescence sensing of saccharides, extensive research has been conducted to design molecular probes and nanoparticles made of different materials. This paper aims to provide in-depth discussion of three main topics that cover the current status of the carbohydrate sensing based on the fluorescence sensing mechanism, including a phenylboronic acid-based sensing platform, non-boronic acid entities, as well as an enzyme-based sensing platform. It also highlights efforts made to understand the recognition mechanisms and improve the sensing properties of these systems. Finally, we present the challenge of achieving high selectivity and sensitivity recognition of saccharides, and suggest possible future avenues for exploration.

Intelligent Insulin vs. Artificial Intelligence for Type 1 Diabetes: Will the Real Winner Please Stand Up?

Research in the treatment of type 1 diabetes has been addressed into two main areas: the development of "intelligent insulins" capable of auto-regulating their own levels according to glucose concentrations, or the exploitation of artificial intelligence (AI) and its learning capacity, to provide decision support systems to improve automated insulin therapy. This review aims to provide a synthetic overview of the current state of these two research areas, providing an outline of the latest development in the search for "intelligent insulins," and the results of new and promising advances in the use of artificial intelligence to regulate automated insulin infusion and glucose control. The future of insulin treatment in type 1 diabetes appears promising with AI, with research nearly reaching the possibility of finally having a "closed-loop" artificial pancreas.

Functionalization of Framboidal Phenylboronic Acid-Containing Nanoparticles via Aqueous Suzuki-Miyaura Coupling Reactions.

Polymeric nanoparticles with reactive functional groups are an attractive platform for drug carriers that can be conjugated with drugs through a cleavable covalent linkage. Since the required functional groups vary depending on the drug molecule, there is a need for development of a novel post-modification method to introduce different functional groups to polymeric nanoparticles. We recently reported phenylboronic acid (PBA)-containing nanoparticles (BNP) with a unique framboidal morphology created via one-step aqueous dispersion polymerization. Since BNPs have high surface area due to their framboidal morphology and contain a high density of PBA groups, these particles can be used as nanocarriers for drugs that can bind to PBA groups such as curcumin and a catechol-bearing carbon monoxide donor. To further explore the potential of BNPs, in this article we report a novel strategy to introduce different functional groups to BNPs via the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction between the PBA groups and iodo- and bromo-coupling partners. We developed a new catalytic system that efficiently catalyzes Suzuki-Miyaura reactions in water without the need for an organic solvent, as confirmed by NMR. Using this catalyst system, we show that BNPs can be functionalized with carboxylic acids, aldehyde, and hydrazide groups while keeping their original framboidal morphology as confirmed via IR, alizarin red assay, and TEM. Furthermore, the potential of the functionalized BNP in drug delivery applications was demonstrated by conjugating the hydrogen sulfide (H2S)-releasing compound anethole dithiolone to carboxylic acid-functionalized BNPs and show their H2S-releasing capability in cell lysate.

Phenylboronic Acid and Amino Bifunctional Modified Adsorbent for Quickly Separating Phenolic Acids from Crude Extract of Clerodendranthus spicatus and Evaluation of Their Antioxidant and Hypoglycemic Activities.

A novel phenylboronic acid and amino bifunctional modified silica gel (SiO2-NH2-FPBA) was prepared, which was 30-80 µm, had a pore size of 8.69 nm, a specific surface area of 206.89 m2/g, was stable at low temperature, and contained 0.4793 mmol/g of the phenylboronic acid group and 1.6377 mmol/g of the amino group. It was used to develop a rapid separation method for phenolic acids. The results showed that it could adsorb 93.64 mg/g caffeic acid, 89.35 mg/g protocatechuic acid and 79.66 mg/g gallic acid. The adsorption process was consistent with the pseudo-second-order model (R2 > 0.99), and fitted the Langmuir isotherm model well (R2 > 0.99). CH3COOH could effectively desorb phenolic acids (>90%) and did not destroy their structures. When SiO2-NH2-FPBA was added to crude extract of Clerodendranthus spicatus, 93.24% of the phenolic acids could be captured, and twenty-two kinds of phenolic acids were identified by Q Exactive HF LC-MS. Furthermore, the isolated phenolic acids from Clerodendranthus spicatus possessed great DPPH, ABTS, and hydroxyl radicals scavenging activities and ferric reducing power. They also demonstrated effective inhibition of α-amylase and α-glucosidase activities (IC50 = 110.63 ± 3.67 µg/mL and 64.76 ± 0.30 µg/mL, respectively). The findings indicate that SiO2-NH2-FPBA has significant potential in practical applications of separating active constituents from natural resources.

Efficient pH-Responsive Nano-Drug Delivery System Based on Dynamic Boronic Acid/Ester Transformation.

Chemotherapy is currently one of the most widely used treatments for cancer. However, traditional chemotherapy drugs normally have poor tumor selectivity, leading to insufficient accumulation at the tumor site and high systemic cytotoxicity. To address this issue, we designed and prepared a boronic acid/ester-based pH-responsive nano-drug delivery system that targets the acidic microenvironment of tumors. We synthesized hydrophobic polyesters with multiple pendent phenylboronic acid groups (PBA-PAL) and hydrophilic PEGs terminated with dopamine (mPEG-DA). These two types of polymers formed amphiphilic structures through phenylboronic ester linkages, which self-assembled to form stable PTX-loaded nanoparticles (PTX/PBA NPs) using the nanoprecipitation method. The resulting PTX/PBA NPs demonstrated excellent drug encapsulation efficiency and pH-triggered drug-release capacity. In vitro and in vivo evaluations of the anticancer activity of PTX/PBA NPs showed that they improved the pharmacokinetics of drugs and exhibited high anticancer activity while with low systemic toxicity. This novel phenylboronic acid/ester-based pH-responsive nano-drug delivery system can enhance the therapeutic effect of anticancer drugs and may have high potential for clinical transformations.

Single-Molecule Sensing of Acidic Catecholamine Metabolites Using a Programmable Nanopore.

Acidic catecholamine metabolites, which could serve as diagnostic markers for many diseases, demonstrate an importance of accurate sensing. However, they share a highly similar chemical structure, which is a challenge in the design of sensing strategies. A nanopore may be engineered to sense these metabolites in a single molecule manner. To achieve this, a recently developed programmable nano-reactor for stochastic sensing (PNRSS) technique adapted with a phenylboronic acid (PBA) adaptor was applied. Three acidic catecholamine metabolites, including 3,4-dihydroxyphenylacetic acid (DOPAC), 3,4-dihydroxymandelic acid (DHMA) and 3-methoxy-4-hydroxymandetic acid (VMA) were investigated by PNRSS. Specifically, DHMA, which contains an α-hydroxycarboxylate moiety and an adjacent cis-hydroxyl groups on its benzene ring, reports two binding modes simultaneously resolvable by PNRSS. Assisted with the high resolution of PNRSS, direct regulation of these two binding modes by pH can also be observed. A custom machine learning algorithm was also developed to achieve automatic event classification.

Abnormal Glycosylation in Cancer Cells and Cancer Stem Cells as a Therapeutic Target.

Tumor resistance and recurrence have been associated with the presence of cancer stem cells (CSCs) in tumors. The functions and survival of the CSCs have been associated with several intracellular and extracellular features. Particularly, the abnormal glycosylation of these signaling pathways and markers of CSCs have been correlated with maintaining survival, self-renewal and extravasation properties. Here, we highlight the importance of glycosylation in promoting the stemness character of CSCs and the current strategies for targeting abnormal glycosylation toward generating effective therapies against the CSC population.

Cytosolic Protein Delivery for Intracellular Antigen Targeting Using Supercharged Polypeptide Delivery Platform.

Despite the well-recognized clinical success of therapeutic proteins, especially antibodies, their inability to penetrate the cell membrane restricts them to secretory extracellular or membrane-associated targets. Developing a direct cytosolic protein delivery system would offer unique opportunities for intracellular target-related therapeutic proteins. Here, we generated a supercharged polypeptide (SCP) with high cellular uptake efficiency, endosomal escape ability, and good biosafety and developed an SCP with an unnatural amino acid containing the phenylboronic acid (PBA) group, called PBA-SCP. PBA-SCP is capable of potently delivering proteins with various isoelectric points and molecular sizes into the cytosol of living cells without affecting their bioactivities. Importantly, cytosolically delivered antibodies remain functional and are capable of targeting, labeling, and manipulating diverse intracellular antigens. This study demonstrates an efficient and versatile intracellular protein delivery platform, especially for antibodies, and provides new possibilities for expanding protein-based therapeutics to intracellular "undruggable" targets.

NMR Investigation of the Supramolecular Complex Formed by a Phenylboronic Acid-Ferrocene Electroactive Probe and Native or Derivatized ß-Cyclodextrin.

Specifically designed electrochemical sensors are standing out as alternatives to enzyme-based biosensors for the sensing of metabolites. In our previous works, we developed a new electrochemical assay based on cyclodextrin supramolecular complexes. A ferrocene moiety (Fc) was chemically modified by phenylboronic acid (4-Fc-PB) and combined with two different kinds of cyclodextrins (CDs): ß-CD and ß-CD modified by a dipicolylamine group (dpa-p-HB-ß-CDs) for the sensing of fructose and adenosine-triphosphate (ATP), respectively. The aim of the present work is to better comprehend the features underlining the aforementioned complex formation. For the first time, a study about inclusion phenomena between the 4-Fc-PB electroactive probe with ß-CD and with dpa-p-HB-ß-CD was performed by using nuclear magnetic resonance (NMR) analysis. In particular, we focused on providing insights on the interaction involved and on the calculation of the binding constant of 4-Fc-PB/ß-CD supramolecular complex, and elucidation about a drift in the time observed during the control experiments of the electrochemical measurements for the 4-Fc-PB/dpa-p-HB-ß-CD supramolecular complex. In this sense, this paper represents a step further in the explanation of the electrochemical results obtained, pointing out the nature of the interactions present both in the formation of the inclusions and in the sensing with the analytes.

Facile Synthesis of Functionalized Phenoxy Quinolines: Antibacterial Activities against ESBL Producing Escherichia coli and MRSA, Docking Studies, and Structural Features Determination through Computational Approach.

The synthesis of new 6-Bromoquinolin-4-ol derivatives (3a-3h) by Chan-Lam coupling utilizing different types of solvents (protic, aprotic, and mixed solvents) and bases was studied in the present manuscript. Furthermore, their potential against ESBL producing Escherichia coli (ESBL E. coli) and methicillin-resistant Staphylococcusaureus (MRSA) were investigated. Commercially available 6-bromoquinolin-4-ol (3a) was reacted with different types of aryl boronic acids along with Cu(OAc)2 via Chan-Lam coupling methodology utilizing the protic and aprotic and mixed solvents. The molecules (3a-3h) exhibited very good yields with methanol, moderate yields with DMF, and low yields with ethanol solvents, while the mixed solvent CH3OH/H2O (8:1) gave more excellent results as compared to the other solvents. The in vitro antiseptic values against ESBL E. coli and MRSA were calculated at five different deliberations (10, 20, 30, 40, 50 mg/well) by agar well diffusion method. The molecule 3e depicted highest antibacterial activity while compounds 3b and 3d showed low antibacterial activity. Additionally, MIC and MBC standards were calculated against the established bacteria by broth dilution method. Furthermore, a molecular docking investigation of the derivatives (3a-3h) were performed. Compound (3e) was highly active and depicted the least binding energy of -5.4. Moreover, to investigate the essential structural and physical properties, the density functional theory (DFT) findings of the synthesized molecules were accomplished by using the basic set PBE0-D3BJ/def2-TZVP/SMD water level of the theory. The synthesized compounds showed an energy gap from 4.93 to 5.07 eV.

Wearable Bifocal Contact Lens for Continual Glucose Monitoring Integrated with Smartphone Readers.

Commercial implantable continuous glucose monitoring devices are invasive and discomfort. Here, a minimally-invasive glucose detection system is developed to provide quantitative glucose measurements continually based on bifocal contact lenses. A glucose-sensitive phenylboronic acid derivative is immobilized in a hydrogel matrix and the surface of the hydrogel is imprinted with a Fresnel lens. The glucose-responsive hydrogel is attached to a commercial soft contact lens to be transformed into a bifocal contact lens. The contact lens showed bifocal lengths; far-field focal length originated from the contact lens' curvature, and near-field focal length resulting from the Fresnel lens. When tear glucose increased, the refractive index and groove depth of the Fresnel lens changed, shifting the near-field focal length and the light focusing efficiency. The recorded optical signals are detected at an identical distance far from the contact lens change. The bifocal contact lens allowed for detecting the tear glucose concentration within the physiological range of healthy individuals and diabetics (0.0-3.3 mm). The contact lens rapidly responded to glucose concentration changes and reached 90% of equilibrium within 40 min. The bifocal contact lens is a wearable diagnostic platform for continual biomarker detection at point-of-care settings.