共找到 20 条结果
Peptide therapeutics have emerged as a versatile class of biomolecules bridging the gap between small-molecule drugs and large biologics. Advantages of such molecules include high target specificity, potent bioactivity and reduced off-target toxicity. Despite these, broader clinical translation remains constrained by inherent limitations like poor metabolic stability, rapid renal clearance, limited membrane permeability and scalable synthesis. This review aims to systematically integrate advances in peptide science across natural discovery, synthetic methodologies, structural engineering, and translational delivery systems, while identifying critical research gaps hindering clinical adoption. We highlight diverse natural sources of bioactive peptides, including plant- (lunasin), animal- (Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP)), microbial- (nisin and cyclosporine), marine- (dolastatins) and venom-derived (chlorotoxin and ω-conotoxin MVIIA (ziconotide)) agents. Advances in solid-phase peptide synthesis (SPPS), green chemistry, and catalytic strategies are discussed alongside emerging in silico approaches, including artificial intelligence-driven sequence design and molecular modeling. Structural modifications such as cyclization, hydrocarbon stapling, PEGylation, and lipidation are critically evaluated for their role in enhancing pharmacokinetic and pharmacodynamic properties. Furthermore, nanoformulation strategies, including self-assembling peptides and cell-penetrating systems, are examined for their potential to overcome biological barriers. Importantly, this review identifies key unresolved challenges, including the lack of predictive models for peptide delivery systems, safety concerns associated with long-term modifications, and limited in vivo validation of naturally derived peptides. Addressing these gaps through integrated computational and experimental approaches will be essential for advancing next-generation peptide therapeutics. Collectively, this work provides a comprehensive framework for the rational design and translation of peptide-based precision medicines.
The concept of bacterial therapy dates back over a century to clinical observations that incidental infections could induce tumor regression. Recent advances in genetic engineering and synthetic biology have since transformed bacteria into versatile living therapeutics with significant preclinical potential against diseases such as cancer, inflammatory disorders, and metabolic conditions. However, clinical translation faces considerable hurdles. Here, we provide a clinically oriented perspective on the translational gap in bacterial therapy. Drawing inspiration from the success of antibody-drug conjugates in achieving precise payload delivery, we highlight an emerging paradigm of "precision living therapeutics" enabled by bacterial surface engineering. we propose the concept of "Tumor accessibility" for the first time, and identify its insufficiency as a critical bottleneck in current therapeutic applications. We then systematically summarize recent advances in bacterial surface engineering, encompassing physical, chemical, and biological strategies, with a focus on their capacity to evade immune clearance, enhance tumor colonization, and improve therapeutic performance. Chemical approaches primarily involve covalent conjugation, including the SpyTag/SpyCatcher system and bioorthogonal click chemistry-based metabolic labeling. Physical strategies center on cell membrane encapsulation and surface coatings such as layer-by-layer encapsulation. Biological strategies include cell camouflage and genetic modulation of surface structures, display of functional biomolecules, and affinity-based systems such as biotin-streptavidin interactions. Finally, we discuss integrative strategies that combine surface-engineered bacteria with conventional treatment modalities, including physical therapy, chemotherapy, and immunotherapy. We propose that future clinical translation of bacterial therapy should shift from localized modification design to a holistic consideration of systemic accessibility.
Membrane-associated biomolecules, primarily proteins, are key enablers of communication, responsiveness, and complexity in natural living cells. Aiming to mimic these capabilities, there is growing interest in equipping bottom-up synthetic cells with membrane-associated biomolecular components. In this review, we focus on how proteins and nucleic acids have been associated with synthetic cell membranes, particularly lipid vesicles, to enable the transmission of signals across the membrane. We discuss strategies for anchoring these biomolecules into lipid bilayers and review how they can enable essential signalling mechanisms in synthetic cells, including cell tethering, the generation and fusion of vesicles, and signal transmission and transduction. We highlight how proteins offer native biological functionality, while nucleic acids may bring more modularity and control. Advancing this area will be essential for realising synthetic systems capable of studying natural communication mechanisms and unlocking applications in biosensing, therapeutics, and synthetic tissue engineering.
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, driven largely by pronounced molecular heterogeneity and delayed clinical detection. Although high-throughput sequencing technologies have substantially advanced the understanding of CRC biology, their routine clinical implementation remains constrained by high costs, infrastructural requirements, and limited accessibility. This review addresses these translational barriers by systematically synthesizing circulating transcriptomic and proteomic biomarkers within a clinically scalable framework. Particular emphasis is placed on biomolecules detectable using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), two widely accessible platforms that underwent extensive global optimization during the COVID-19 pandemic and are readily adaptable to liquid biopsy workflows. Through a stage-resolved analysis, we identify 9 genomic and 7 proteomic biomarkers associated with early-stage (I-II) CRC, alongside 9 genomic and 4 proteomic biomarkers linked to advanced-stage (III-IV) disease progression. Beyond biomarker cataloging, these molecules are integrated with Cancer Hallmark pathways, clinical-stage associations, and available clinical trial evidence to evaluate their biological relevance and translational readiness. In addition, we summarize standardized operating procedure (SOP) considerations and multiplex detection strategies to improve assay reproducibility, scalability, and cross-border clinical implementation. Collectively, this review bridges molecular discovery with clinically deployable laboratory workflows and provides a translational roadmap for the development of affordable, liquid biopsy-based diagnostic strategies aimed at improving CRC detection, patient stratification, longitudinal monitoring, and early therapeutic intervention. Stage-resolved biomarker framework: Provides an integrated catalog of circulating transcriptomic and proteomic biomarkers stratified across CRC stages I–IV.Mechanistic and functional integration: Links circulating biomarkers with Cancer Hallmark pathways, highlighting biomolecules that function as both diagnostic indicators and molecular regulators of disease progression.Clinically scalable diagnostic focus: Prioritizes RT-PCR– and ELISA-based detection strategies to support affordable, high-throughput, and clinically accessible liquid biopsy applications.Translational readiness: Integrates clinical trial evidence, assay feasibility, and SOP considerations to strengthen the clinical applicability and reproducibility of candidate biomarkers.Multi-analyte precision diagnostics: Supports the development of combined transcriptomic–proteomic biomarker panels to improve diagnostic sensitivity, prognostic stratification, and disease monitoring.Global clinical applicability: Proposes a practical framework for biomarker implementation and validation across diverse healthcare systems, including resource-limited settings.
Neurological illnesses continue to be a major global health challenge and require novel and safe therapeutic strategies. Blue foods like marine fish, algae, and invertebrates consist of many bioactive proteins/peptides that might provide multiple benefits for maintenance of a healthy brain, including neuroprotection, reduction of inflammation, and reduction of oxidative stress. This review looks at both recent advances made with blue food bio-molecules and their potential future roles in therapeutic targeting for neurological disorders. This study is designed as a narrative review, aiming to comprehensively summarize and critically analyze existing literature on marine-derived bioactive peptides and their neuroprotective potential. Literature searches were conducted from January 2009 to March 2025 using PubMed and other biomedical databases. Available preclinical evidence suggests that marine-derived proteins and peptides may exert neuroprotective effects through multiple mechanisms, including activation of antioxidant defense pathways via Nrf2-mediated signaling, modulation of NF-κB-associated neuroinflammatory responses, regulation of serotonergic and dopaminergic neurotransmission, and attenuation of amyloid-β aggregation. Experimental studies conducted in animal models have reported improvements in cognitive performance, reductions in oxidative stress biomarkers, and decreased production of pro-inflammatory cytokines following administration of marine protein hydrolysates. Clinical translation of marine-derived bioactive peptides remains challenging due to the following factors: standardization of extraction, bioavailability, batch-to-batch variability, allergenic potency, and complex regulatory requirements. Ongoing new approaches using nano-formulation, synthetic biology, and Artificial Intelligence (AI) in the discovery of peptides hold the promise of enhancing their stability, targeting, and scalability. However, in order to validate the therapeutic utility of these approaches, it will require large, well-designed clinical studies.
The ability to access atomically tailored complex peptides and proteins provides powerful opportunities for dissecting molecular functions and advancing applications in chemical biology, therapeutics, and (bio)-materials science. Robust precision-engineering strategies are essential to construct well-defined protein architectures while preserving native folding and activity. To do so, chemoselective bioconjugation techniques have been developed to modify specific side chains of amino acids. This allowed for the selective introduction of functionalities on predetermined amino acids. However, ultimate control can be achieved only through site-selective modifications that precisely define both the nature of the linkage and the exact position of conjugation on elongated peptide sequences or fully assembled proteins. Cysteine residues are of particular interest, as their highly nucleophilic thiols offer excellent chemoselectivity and typically occur in low abundance in their reduced form. Here, we examine chemoselective transformations targeting cysteine residues that have been further refined to occur exclusively at predefined positions within a peptide or protein, thereby achieving a high degree of site-selectivity. This review focuses exclusively on chemical strategies for cysteine modification, offering guidance for future synthetic developments within the field of precision chemistry. Achieving this level of precision requires advanced chemical strategies that exploit the local environment of the targeted cysteine. One approach involves leveraging neighboring functional groups, for example, engaging the thiol together with the α-amine or carboxylate to enable selective N- or C-terminal modification, respectively. In such designs, the cysteine side chain may contribute through transient interactions, direct incorporation into the covalent linkage, or the stabilization of the desired product. Recently, a promising strategy has attracted increasing attention in which site-selectivity is enabled by temporary interaction with a proximal amine, thus being applicable to differentiate also between internal cysteines. Together, these strategies highlight that site-selective protein modification has evolved into a powerful tool for the rational design and functional control of complex biomolecules, redefining what is achievable in chemical biology, therapeutics, and biomaterials science. We anticipate that increasingly routine or user-friendly approaches such as the programmable TriTEx method will further accelerate the adoption of precision biomolecule conjugates in both research and industrial settings.
Sulfhydryl functionality is useful for the chemoselective and site-specific conjugation of biomolecules for medical diagnosis and therapeutic purposes. Several types of thiol-reactive conjugation chemistry have been developed, including a maleimide-based addition reaction. Our previous study showed that activated 6-[18F]-fluoronicotinic acid ([18F]-FNA) ester chemoselectively forms an S-acylated product with peptide ACooP (H-ACGLSGLGVA-NH2) bearing both a free amino group and a sulfhydryl group for positron emission tomography applications. The aim of this work is to better understand the chemoselectivity of S-acylation and explore its potential use for site-specific peptide radiolabeling. Accordingly, three new peptide variants of the decapeptide ACooP were designed as model sequences bearing both free amino and sulfhydryl functionalities, with the cysteine residue located at different positions in the sequences. The peptide variants C@3 (H-AGCLSGLGVA-NH2), C@4 (H-AGLCSGLGVA-NH2), and C@5 (H-AGLSCGLGVA-NH2) were conjugated with FNA to prepare the corresponding nonradioactive reference compounds. The conjugated products were characterized using one- and two-dimensional nuclear magnetic resonance analysis and high-resolution mass spectrometry. Peptide radiolabeling tests were performed using [18F]-FNA 4-nitrophenyl ester as the prosthetic group at pH 8.6 and 7.4. The radiolabeled products were S-acylated compounds with high or exclusive chemoselectivity (>95%) in all three cases. To demonstrate the utility of this type of chemoselective S-acylation for radiotracer preparation, [18F]-FNA-S-C@5 was prepared with a radiochemical purity of 97.0% ± 0.8 (n = 3) and a decay-corrected radiochemical yield of 16.1% ± 3.5. A batch size of the end product with hundreds of MBq was easily achieved, which is sufficient for PET imaging applications. [18F]-FNA-S-C@5 showed limited in vitro stability in rat plasma, with intact tracer observed at 13.1% ± 4.2 (n = 3) after 15 min of incubation. In conclusion, chemoselective S-acylation-based peptide radiolabeling was achieved using [18F]-FNA 4-nitrophenyl ester, and this reaction holds promise for highly chemoselective and site-specific radiolabeling of other types of biomolecules.
Large poly(ethylene) glycol (PEG) chains are often conjugated to proteins or biomolecules to inhibit proteolytic degradation, mask immunogenic response, reduce clearance rates, and improve biodistribution of therapeutics, vaccines, drug delivery systems, and gene therapy formulations. The PEG macromolecular chain can also be used as a noninvasive reporter to track biologics in vivo by magnetic resonance spectroscopy (MRS). Rapid internal dynamics of PEG render the transverse 1H spin relaxation time to be comparable to water (~0.5 s) and amenable to imaging through traditional pulsed field gradient techniques. While water signal grossly exceeds that of PEG it is possible to filter 1H MRS signal of PEGylated conjugates through one of two ways-(1) stimulated echo acquisition mode (STEAM) MRS, which leverages huge differences in the diffusion of water versus PEGylated constructs, and (2) 13C-edited 1H MRS of fully 13C-enriched PEGylated constructs. Here, we compare both approaches. A 15 kDa 13C-enriched PEG chain was prepared alone, conjugated to bovine serum-albumin (BSA), and incorporated into a 52-nm-diameter PEG-poly(lactic acid) (PLA) nanoparticle. These three PEG constructs were then separately monitored in real time by 13C-edited 1H MRS, after introducing them into rat animal models intravenously. A 13C-editing scheme was employed to monitor 1H MRS PEG signal in the vasculature via a radiofrequency coil placed around the tail. An observed two-component decay of the PEG signal is attributed to perfusion and early equilibration (alpha phase) and slow clearance (beta phase). 13C-PEG alone, 13C-PEG-BSA, and 13C-PEG-PLA nanoparticles exhibited half-lives of 38.6 min, 23.4 h, and 11.9 h, respectively. The relatively rapid clearance rates associated with the PEG-PLA nanoparticles is expected to arise from enzymatic degradation of the PLA chain. Using STEAM-based editing schemes, we then evaluated sensitivity and water suppression in diffusion-edited 1H MRS for (12C)-PEGylated BSA contrasting 2-, 20-, and 40-kDa PEG chains, in imaging phantom samples. Larger molecular weight PEG chains (i.e., 40 kDa) proved far superior to smaller PEG chain reporters due to reduced inhomogeneities and longer T2, upon employing either a 13C-HQMC filter or a STEAM-based diffusion filter.
Liposomal or polymeric nanoparticles have been instrumental in improving the delivery of poorly soluble chemotherapeutics and those with dose limiting toxicity such as doxorubicin (DOX). More recently, nanoformulations have been shown to enable simultaneous delivery of emerging biomolecules such as siRNA. However, for larger nucleic acids such as mRNA, this remains challenging. In this study, we developed a poly(β-amino ester) (PBAE) based platform, capable of co-formulating mRNA and doxorubicin into nanoparticles. To demonstrate proof of concept using therapeutically relevant cargo, immunomodulatory interleukin-12 (IL-12) was selected as a model mRNA. IL-12 is a pro-inflammatory cytokine that promotes anti-tumour immunity partly through amplifying effector cytokines such as interferon-γ (IFNγ). We found that PBAE complexed DOX and mRNA into positively charged nanoparticles of 120 nm and size-exclusion chromatography indicated a DOX loading efficiency of over 97%. Co-association of both DOX and mRNA was characterised at a single nanoparticle level by nano-flow cytometry. Following delivery to B16F10 murine melanoma cells, more than 95% of cells were double-positive for DOX and Cy5-labelled mRNA, and confocal microscopy confirmed co-localised regions of DOX with mRNA. Interestingly, nanoformulated DOX had increased nuclear accumulation by 1.7-fold relative to free DOX, which correlated with a significantly reduced cell viability of 12.9% with PBAE-DOX/mRNA, compared to 26.6% for free DOX at the same dose. Moreover, despite this strong cytotoxic effect, reporter mRNA translation remained robust, with luciferase expression approximately two orders of magnitude above non-transfected controls at the highest DOX doses. Co-formulation of IL-12 mRNA and DOX with PBAE demonstrated effective IL-12 protein secretion in transfected B16F10 cells with a simultaneous DOX dose dependent reduction in viability. Secreted IL-12 was bioactive, inducing dose-dependent STAT4 phosphorylation and IFNγ secretion in primary mouse splenocytes. Furthermore, in a syngeneic melanoma mouse model, intratumoural administration of PBAE-DOX/IL-12 mRNA achieved significantly elevated levels of IL-12 and IFNγ in the tumour compared to the saline control, confirming delivery of DOX, as well as IL-12 protein secretion, and immunostimulatory activity in vivo. These findings demonstrate that PBAE is a promising platform for co-delivery of cytokine encoded mRNA with DOX in a single formulation, establishing feasibility for advanced chemoimmunotherapy approaches.
Water-soluble conjugated polymers (WSCPs) represent an important class of functional macromolecules that combine the electronic advantages of π-conjugated polymer backbones with aqueous processability, biocompatibility, and tunable biointerfacial behavior. Unlike conventional small-molecule photosensitizers or inorganic nanomaterials, WSCPs offer polymeric design flexibility through controlled backbone engineering, side-chain functionalization, amphiphilicity, charge density, molecular weight, and nanoparticle self-assembly. These structural parameters govern their optical absorption, fluorescence emission, exciton migration, reactive oxygen species generation, photothermal conversion, colloidal stability, cellular uptake, and interactions with biomolecules. This review discusses the fundamental polymeric principles underlying WSCP performance, including π-electron delocalization, light-harvesting amplification, Förster resonance energy transfer, electrostatic complexation, hydrophobic association, and stimulus-responsive conformational changes. Particular emphasis is placed on how charged, PEGylated, glycosylated, and amphiphilic side chains improve water solubility, reduce nonspecific interactions, and enable targeted interactions with nucleic acids, proteins, membranes, and tumor cells. The review further summarizes the use of WSCPs and conjugated polymer nanoparticles in photodynamic therapy, photothermal therapy, antimicrobial treatment, drug delivery, and gene delivery. In photodynamic and photothermal applications, WSCPs act as light-responsive therapeutic platforms by generating singlet oxygen or other reactive oxygen species, converting absorbed light into localized heat, or combining both effects for synergistic therapy. In drug and gene delivery, their hydrophobic conjugated domains, cationic functionalities, and intrinsic fluorescence enable payload encapsulation, nucleic acid condensation, real-time tracking, and triggered release. Overall, WSCPs provide a versatile polymer-based platform for theranostic medicine, where molecular structure, photophysics, and biofunctionality can be rationally integrated to improve imaging, therapeutic efficacy, and targeted delivery.
Nano-sized outer membrane vesicles (OMVs) are lipid-bilayered structures that primarily encapsulate periplasmic components, with minor inclusion of cytoplasmic materials. Rather than passive byproducts of cellular damage, OMVs are now understood as active mediators of bacterial physiology, environmental adaptation, and host interaction. Recent evidence identifies envelope instability as a key mechanistic driver of OMV biogenesis. Disruptions in outer membrane-peptidoglycan connectivity, imbalances in periplasmic homeostasis, and alterations in lipid asymmetry collectively promote vesicle formation as a regulated adaptive response. Under stress conditions, OMVs acquire specialized functional roles, selectively enriching specific cargo and exhibiting surface properties that enable them to sequester host-derived antimicrobial factors. OMV-associated biomolecules further influence vesicle uptake into host cells through distinct endocytic pathways, shaping intracellular trafficking and downstream functional outcomes. Following internalization, pathogen-derived OMVs disrupt host signaling pathways and are exploited to promote immune evasion, whereas commensal-derived OMVs contribute to microbiota homeostasis and immune modulation. In parallel, growing efforts to harness OMVs as vaccine platforms highlight their potential as innovative tools for both therapeutic and prophylactic applications. Collectively, these insights position OMVs as critical mediators of bacterial pathogenicity and as promising targets for anti-infective strategies.
The present study re-examines the efficacy of prevalent methods of Thymoquinone (TQ) estimation in the biomass of Nigella sativa L. using RP-HPLC. The differential efficacy in terms of magnitude, accuracy and cognate correlation with metabolically affiliated groups of biomolecules, phenolics, and antioxidants opens new vistas.  The study was conducted to develop a more accurate and sensitive method for quantitative assessment and correlation among TQ content, total phenolics, and flavonoids in six different plant parts of Nigella sativa, which are used in culinary applications, therapeutic formulations, nutraceuticals, and biowaste. The re-examination was based on the extraction of TQ-rich fractions with solvents of differential polarity (methanol and benzene), followed by quantitative assessment by RP-HPLC using methanol: water (80:20) as the mobile phase. RP-HPLC data revealed that TQ in methanolic extracts was highest in root (0.00959 ± 0.00032 mg/g FW), followed by flower (0.00882 ± 0.00013 mg/g FW), and lowest in fruit (0.00488 ± 0.00014 mg/g FW). Benzene extracts yielded the same pattern but with substantially higher magnitude, particularly in flower (0.0634 ± 0.0272 mg/g FW ) and fruit (0.0616 ± 0.0416 mg/g FW), making the system more resolvable. With the objective to understand the correlation with compounds of antioxidant nature, total phenolic content (TPC) and total flavonoid content (TFC) were determined and correlated with TQ content estimated using two different solvents. TPC was highest in leaf (0.208 ± 0.010 mg GAE/g) and lowest in fruit. TFC was highest in bud (0.344 ± 0.004 mg QE/g) and lowest in root. Pearson correlations using triplicate values showed very weak associations between methanolic TQ and TPC (r = 0.008; p < 0.05) and between methanolic TQ and TFC (r = -0.330; p < 0.05). Benzene-extracted TQ also showed a negligible positive correlation with TPC (r = 0.110; p < 0.01) and a very poor negative correlation with TFC (r = -0.016; p< 0.01). TPC and TFC remained moderately positively correlated (r = 0.450; p = 0.05). The results indicate that TQ and phenols accumulate largely independently in different plant parts of N. sativa. The TQ estimation using benzene extracts appears far superior to the method relying on methanolic extracts, given the large-scale and magnitude differences, making it more resolvable during screening.
The escalating global cancer burden, particularly in low- and middle-income countries, necessitates safer and more effective therapeutic strategies. The toxicity and environmental issues of traditional heavy-metal-based quantum dots (QDs) have been addressed by green-synthesised QDs, which have become a promising platform for nanomedicine. In photodynamic treatment (PDT), photothermal therapy (PTT), and theranostic applications, the anticancer effectiveness of green-synthesized QDs that are derived from plant extracts, microbes, biomolecules, and biomass waste is critically assessed. Green synthesis techniques, such as hydrothermal and microwave-assisted methods, provide biocompatible QDs with good photostability, tunable optical characteristics, and decreased cytotoxicity. Mechanistically, these QDs generate reactive oxygen species (ROS), induce mitochondrial dysfunction, produce localized hyperthermia upon near-infrared irradiation, and activate apoptotic pathways (such as p53, Bax/Bcl-2, and caspase cascade), leading to selective cancer cell death. Preclinical in vitro and in vivo studies demonstrate potent tumor ablation through passive (EPR effect) and active targeting strategies. Despite these advances, some key setbacks hinder their clinical translation: lack of standardized synthesis protocols, batch-to-batch variability, limited long-term biosafety data, suboptimal targeting efficiency, and regulatory hurdles. Future perspectives include AI-driven optimization, smart theranostic platforms integrating multimodal imaging and therapy, and sustainable circular economy approaches using biowaste. Addressing these challenges through harmonized protocols and rigorous preclinical validation will be essential to realize the full potential of green-synthesized QDs as safe, multifunctional, and effective cancer nanomedicines.
Porphyrins are a class of cyclic organic compounds characterized by a large conjugated system, which allows for unique optical properties and strong interactions with various biomolecules. Due to their versatile structures, porphyrins have gained significant attention in biomedical applications, particularly in drug delivery systems. This review paper focuses on the recent advancements in porphyrin-based inorganic materials utilized for drug delivery, emphasizing their potential to enhance therapeutic efficacy while minimizing side effects. This review divides porphyrin-based materials into dendrimers, nanocarriers, and functionalized nanoparticles. Details on synthesis, drug loading capacity, release profiles, and biocompatibility are provided for each type. Porphyrin-functionalized nanoparticles can selectively target cancer cells, making them promising anticancer drug delivery vehicles. Conjugating porphyrins with targeting ligands or antibodies improves selectivity and treatment options. Photodynamic therapy with porphyrins is another important topic in this review. Photodynamic therapy is an innovative method that produces reactive oxygen species from lightactivated porphyrins and oxygen, damaging cancer cells locally. The review discusses how Photodynamic therapy with drug delivery systems can improve anticancer drug efficacy while reducing systemic toxicity. The review also discusses ways to improve porphyrin solubility and stability, which are crucial for clinical use. The review also discusses porphyrin-based drug delivery systems drawbacks. Porphyrin compounds' stability, phototoxicity, and complex interactions with biological environments are among these issues. We discuss encapsulation and hybrid systems that combine porphyrins with other materials to overcome these challenges.
Diabetes mellitus represents a major global health challenge with rapidly increasing prevalence and substantial morbidity driven by metabolic and vascular complications. Extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication and are increasingly implicated in the pathogenesis and progression of diabetes. This review summarizes current knowledge on EV biology, including their classification, cellular sources, biogenesis, uptake mechanisms, and molecular cargo. We discuss the contribution of EV-associated microRNAs to immune dysregulation and β-cell damage in type 1 diabetes mellitus (T1DM), as well as the role of EVs in insulin resistance, metabolic signaling, and vascular dysfunction in type 2 diabetes mellitus (T2DM). Particular emphasis is placed on EV-mediated modulation of endothelial function, angiogenesis, and tissue repair, alongside their involvement in the impairment of insulin receptor integrity. We further explore how lifestyle factors may influence EV composition and function, highlighting their potential integration into preventive strategies. Finally, we evaluate the emerging therapeutic potential of EVs as biomarkers and delivery systems, while addressing current limitations and future directions. Collectively, EVs represent a promising frontier in understanding diabetes pathophysiology and developing innovative diagnostic and therapeutic approaches. Unlike previous reviews that examine EVs separately as biomarkers or therapeutic vehicles, this review integrates emerging evidence supporting EVs as mediators of systemic communication linking pancreatic islets, adipose tissue, immune cells, vascular endothelium, kidney, heart, and retina throughout diabetes progression. We further critically evaluate translational barriers that currently limit clinical implementation of EV-based diagnostics and therapeutics.
In medicine, nanoparticles are used for various purposes, including theranostics, imaging, diagnostics, drug delivery, tissue regeneration and targeted cancer treatments, and to minimize the harmful side effects associated with conventional therapies. Target-specific biomolecules, such as silica nanoparticles (SiNPs) labeled with metallic radionuclides, are becoming increasingly popular. The choice of radionuclide is based on its nuclear properties. Silica has several advantages for nanoparticle synthesis, including high biocompatibility, the capacity for drug encapsulation due to its porous structure, and the potential for extensive surface functionalization, including radiolabeling for imaging and therapeutic applications. A radionuclide can be attached to a silica nanoparticle either directly or through the use of chelators or polymers. Additionally, the capability to encapsulate therapeutic agents within such systems offers significant potential for the development of targeted therapies. This study aims to provide a comprehensive overview of recent developments in the radiolabeling of silica-based nanoparticles, with a focus on their application in nuclear medicine, particularly in diagnostic imaging and targeted radionuclide therapy. Theranostics employs a range of imaging modalities to guide and monitor therapeutic interventions. Principal techniques include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and Optical Imaging (such as fluorescence and bioluminescence). These imaging methods enable precise visualization of pathological sites, facilitate tracking of therapeutic agent distribution, and permit real-time assessment of treatment efficacy.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive joint inflammation and damage. Early clinical diagnosis is crucial for effective intervention but presents significant challenges due to an initial asymptomatic inflammatory phase. Anti-citrullinated-protein antibodies (ACPA) and rheumatoid factor (RF) detection have been useful in early RA diagnosis, but their reliability is debatable as they are often non-specific. This has prompted a quest for alternative, more robust biomarkers. Researchers have turned to advanced proteomic and glycosylation analyses of biological fluids (e.g., synovial fluid, plasma and serum) and tissues using techniques such as MALDI-MS, Q-TOF, and SELDI-TOF. These approaches may offer a comprehensive approach to scrutinize a range of biomolecules as potential RA biomarkers, from citrullinated-proteins and peptides to novel potential protein biomarkers such as thymosin, macrophage-capping protein, calgranulins, and serum amyloid-A. Further, proteomics-based approaches have the ability to specifically monitor changes in the RA proteome (e.g., glycosylated VCAM1/SEMA4D proteins and GFAP/A1BG auto-antibodies) to unearth potential diagnostic and prognostic candidates. Disease monitoring in response to anti-rheumatic drugs using treatment-responsive markers, such as S100A8/A9 heterocomplex and leucine-rich alpha-2 glycoprotein, is another application of proteomics-based technologies. In view of the significance of prediction, early diagnosis and monitoring of RA symptomatology, this review discusses the potential utilities of proteinaceous species as proteomics-based biomarkers that may provide insights into disease mechanisms and offer potential avenues for personalized therapeutic interventions to revolutionize RA management.
Early detection of diseases associated with gasotransmitters and biothiols is crucial for improving therapeutic outcomes and increasing patient survival rates. Although metal-complex-based optical probes (metalloprobes) show promise for diagnostic uses, the healthcare community has not yet reached a consensus on their clinical utility. From the perspective of a coordination chemist, this review delves into the design and applications of metalloprobes for detecting gasotransmitters and biothiols, presenting a vital step for advancing clinical diagnostics in human healthcare. By highlighting the related prior studies, which have substantially contributed to the field during 2000-2024, the review sheds light on the needs, opportunities, challenges, and latest developments in the field of metalloprobes. It discusses the fundamental principles of metal-luminophore coordination, signal transduction mechanisms, detection thresholds, and real-time applications in complex biological matrices such as human blood plasma, serum, urine, and also offers insights into cellular investigations. Additionally, the review offers a critical discussion and analysis of the advantages and limitations of metalloprobes, with an emphasis on future challenges and opportunities for commercializing task-specific metalloprobes in the point-of-care testing (POCT) market. We envisage that this careful review will inspire further research to reveal the intricate roles of these biomolecules and driving innovations in bioassays, and therapeutic interventions for complex diseases (innovations-to-implementations, I-2-I).
Breast cancer remains a leading cause of cancer morbidity and mortality worldwide. Although nanomedicines are a promising and rapidly evolving therapeutic platform, their clinical translation remains limited. Depending on the stage and subtype of the disease, systemic treatments and localized strategies are still essential for treating metastatic breast cancer. Metastatic forms are still mostly incurable, even with improvements in early-stage interventions. Low tumor specificity, high systemic toxicity, decreased chemical stability, and multidrug resistance are some of the drawbacks of traditional treatments. Biomimetic nanoparticles (BMNPs) are synthetic cores cloaked with native cell membranes or biomolecules to recapitulate biological surface functionality for improved targeting and immune evasion. They have synthetic structures and artificial antigen-presenting cells in addition to coatings made of biologically derived materials. In preclinical studies, BMNPs often show enhanced tumor accumulation, prolonged circulation, and reduced systemic toxicity compared with uncoated nanoparticles, although reporting heterogeneity limits direct comparisons. By circumventing complex bottom-up synthetic approaches that attempt to replicate biological complexity, biomimetic nanoparticles preserve native biological functions using naturally derived cell membranes.
Osteoarthritis (OA) is a leading cause of chronic pain and disability in the elderly. The lack of sensitive diagnostic methods for early OA remains a major clinical challenge. Synovial fluid contains exosomes (SF-exosomes) that carry disease-specific biomolecules, making them promising targets for early diagnosis. However, efficient isolation of SF-exosomes with high purity is technically demanding. This study aimed to develop phosphatidylserine-based molecularly imprinted polymers (P-MIPs) for the efficient enrichment of SF-exosomes and to discover potential protein biomarkers for early OA diagnosis using proteomic analysis. P-MIPs can specifically recognize phosphatidylserine on the extracellular vesicle membrane, thereby achieving highly selective enrichment of extracellular vesicles. P-MIPs were synthesized via a reverse microemulsion system. The binding capacity, specificity, and enrichment efficiency of P-MIPs were characterized. SF-exosomes from 6 OA patients and 6 healthy controls were enriched using P-MIPs and analyzed by LC-MS/MS proteomics. Differentially expressed proteins (DEPs) were subjected to bioinformatics analysis. The diagnostic value of hub genes was validated by ROC analysis in an independent cohort. The results showed that the binding capacity (Qmax) of P-MIPs was 129.71 µmol/g, and the cross-reactivity with sphingomyelin (SM), phenylphosphonic acid (PYP), and tyrosine phosphopeptides was less than 3.5%. The purity of enriched SF-exosomes was 82.6%. A total of 40 DEPs were identified, of which 28 were upregulated and 12 were downregulated in OA. PPI network analyses identified 10 hub genes: IL6, IL1B, MYC, CD4, MMP9, PTPRC, CXCL8, PPARG, ICAM1, and STAT3. ROC analysis showed that among the top five hub genes ranked by degree, MYC (AUC = 0.741) and IL6 (AUC = 0.735) exhibited good diagnostic performance. A combined biomarker panel comprising the top five hub genes achieved an even higher diagnostic accuracy, with an AUC of 0.899. The P-MIPs-based SF-exosome enrichment strategy is efficient and selective. MYC and IL6 are potential diagnostic biomarkers for early OA, and the identified DEPs provide insights into OA pathogenesis. Furthermore, this strategy can be extended for the recognition and enrichment of exosomes in other biological fluid matrices, facilitating the discovery of novel disease biomarkers and therapeutic targets.