Chemo-photothermal therapy (chemo-PTT), which integrates chemotherapy with photothermal ablation, has emerged as a promising strategy for enhancing antitumor efficacy compared with single-modality treatments. However, aggressive malignancies such as melanoma still demand more efficient targeted and imaging-guided therapeutic platforms. The aim of this study was to develop a near-infrared (NIR)-responsive theranostic nanoplatform capable of targeted drug delivery, controlled release, and synergistic chemo-photothermal therapy. For this purpose, gold nanostars (AuNSts) were coated with a thin mesoporous organosilica layer (MOSNPs), followed by doxorubicin (DOX) encapsulation to form AuNSts@MOSNPs@DOX. To improve biocompatibility and prolong systemic circulation, the nanoparticles were further encapsulated in B16F0 cancer cell membranes (CCM), thereby serving as a biomimetic gatekeeper. Finally, Sgc-8c aptamer conjugation yielded the targeted construct, Apt-AuNSts@MOSNPs@DOX@CCM, for melanoma-specific delivery. Notably, this work presents a novel dual-responsive and biomimetic strategy that combines cancer cell membrane camouflage with aptamer-mediated active targeting, thereby enhancing tumor specificity and enabling imaging-guided chemo-photothermal therapy. The nanoplatform exhibited a high DOX loading capacity (31.79% ± 5.4) and loading efficiency (79.45% ± 13.5), along with NIR- triggered drug release. In vitro studies on B16F0 melanoma cells demonstrated significantly increased cellular uptake and cytotoxicity of the aptamer-functionalized nanoparticles under chemo-PTT conditions compared with non-targeted systems (p < 0.001). In vivo evaluation in melanoma-bearing mice revealed that Apt-AuNSts@MOSNPs@DOX@CCM combined with 808 nm laser irradiation induced complete tumor regression, achieved 100% survival, and enhanced computed tomography contrast. Overall, this multifunctional nanoplatform offers a promising targeted, imaging-guided strategy for effective melanoma therapy.
Tumor oxygenation plays a crucial role in enhancing the effectiveness of sono-photodynamic therapy (SPDT). This study aimed to develop Iron-porphyrin-loaded, oxygen-filled, 4T1 cancer cell membrane-based vesicles (NB-POR) as a novel theranostic platform for SPDT to enhance tumor eradication and provide ultrasound contrast. NB-POR with a size of 253.71 ± 20.90 nm exhibited controlled in vitro POR release, which was significantly accelerated after laser irradiation (reaching 100% release after 120 h) or ultrasound pulsing (reaching 100% release after 72 h). In vitro investigations demonstrated that NB-POR can generate hydroxyl radicals and singlet oxygen. In a parallel experiment, intracellular ROS generation was also significantly enhanced upon laser and ultrasound radiation. In vitro assessment of metastatic breast cancer cells (4T1) from mice showed greater cellular toxicity and apoptosis induction by NB-POR following combined laser and ultrasound irradiation. Flow cytometry demonstrated the targeting capability of the 4T1 cell membrane-based carrier toward 4T1 cells. In vivo therapeutic efficacy against 4T1 tumor-bearing BALB/c mice showed very effective anti-cancer activity of this system after combined SPDT, with 3 out of 4 mice cured and tumor-free at the end of the experiment. The safety of this treatment strategy was demonstrated by 100% survival and no significant weight loss. The diagnostic performance of this platform was also investigated in vitro and in vivo, yielding pronounced ultrasound contrast. Overall, the results provided valuable insights supporting the potential clinical application of Iron-porphyrin-loaded, Oxygen-filled biomimetic nanobubble systems for combination therapy.
This review examines the applications of indirect lateral flow assays (ILFAs) and indirect ELISA-based LFAs as robust, paper-based diagnostic platforms for the identification of contaminants in food products. ILFAs employ antibodies, aptamers, and their hybrid composites combined with molecularly imprinted polymers to deliver a cost-effective diagnostic tool. Capable of detecting biological and chemical adulterants within 3 to 30 min, these assays enable efficient identification directly at the point-of-care. The operational principles, the functions of different components, and various assay formats of ILFAs are elaborated, with particular focus on their suitability for monitoring complex food matrices. This review highlights recent progress in ILFA technology, focusing on innovative signal amplification methods and novel labeling techniques designed to enhance sensitivity and reproducibility in food safety testing. Continued developments in ILFA offer significant potential to improve diagnostic accuracy and accessibility within the food industry, thereby supporting stronger regulatory compliance and advancing public health protection.
Neurological disorders are complex and often very challenging for patients. Many of these conditions result from mutations in genes that are essential for normal function. Most existing treatments only alleviate symptoms, highlighting the urgent need for more effective therapeutic strategies. In the current drug development landscape, gene therapy offers hope as a promising approach. Specifically, CRISPR-Cas9 technology enables precise gene editing across diverse cell types and organisms. An increasing number of research groups are investigating innovative therapies and the molecular mechanisms behind neurological diseases. This review highlights the use of CRISPR-based gene therapies for various brain diseases, including multiple sclerosis, Alzheimer's, Parkinson's disease, epilepsy, stroke, and brain tumors. It consistently recognizes significant challenges in clinical applications, including overcoming the blood-brain barrier (BBB), managing off-target effects, ensuring efficient delivery, and addressing immunogenicity and ethical concerns.
MicroRNAs (miRs) are central regulators of tumor initiation and progression, and their aberrant expression patterns have been identified as clinically valuable biomarkers for the early diagnosis of malignancies and prognostic evaluation. Here, we report tag-free fluorescence biosensing platform for the detection of circulating miRs in serum, targeting microRNA-21 (miR-21) and microRNA-10b (miR-10b) as clinically relevant oncogenic markers. The assay integrates CRISPR/Cas12a-mediated signal regulation with complementary strand (CS)-mediated target recognition. In this strategy, target miRs hybridize with the CS, thereby preventing CS-mediated activation of the Cas12a-crRNA complex. As a result, Cas12a collateral cleavage is suppressed, the G-quadruplex reporter remains intact, and Thioflavin T fluorescence is enhanced. The platform demonstrated excellent sequence discrimination capability, effectively distinguishing closely related and mismatched targets. Sensitive quantification was achieved with limits of detection of 1.4 nM for miR-21 and 852 pM for miR-10b. Importantly, robust analytical performance was maintained in complex biological matrices, confirming its applicability to serum samples. Collectively, this CRISPR/Cas12a-enabled fluorescent biosensor provides a simple approach for circulating miR detection.
Wounds pose a significant challenge to both healthcare and the economy, as current therapies often fail to address the complex biology of healing. Exosomes derived from fetal tissue, enriched with regenerative microRNAs and proteins, have demonstrated strong potential in promoting wound repair. Melatonin is an indoleamine with multiple effects, including antioxidant and immunomodulatory activities. It has been shown to promote tissue regeneration; however, it degrades rapidly and has low bioavailability. This study investigates the potential of melatonin-loaded fetal tissue-derived exosomes (MEL@EXO) combined with a pH-responsive, biocompatible hydrogel composed of chitosan, polyvinylpyrrolidone (PVP), hyaluronic acid (HA), and glycerin to accelerate full-thickness wound healing. Fetal tissue-derived exosomes were isolated from Wistar rat fetal tissues using differential centrifugation and PEG-induced extraction. Melatonin was encapsulated by electroporation. Exosomes had the expected size, globular shape, stability, and high melatonin-loading efficiency. The hydrogel was prepared by gradually adding PVP to chitosan dissolved in citric acid under constant stirring, followed by the incorporation of HA and glycerin. The hydrogel showed a pH-responsive sol-gel transition and porous architecture, enabling sustained exosome release. Cytotoxicity evaluation on Human Dermal Fibroblast (HDF cell line) confirmed that the MEL@EXO hydrogel and its components exhibited no cytotoxic effects. Furthermore, the hemolysis test revealed no significant hemolysis, confirming the biocompatibility of the composite. In vivo, MEL@EXO hydrogel accelerated wound closure compared to the control and single-component groups. Histological studies revealed that wounds treated with MEL@EXO were undergoing re-epithelialization, thick collagen deposition, and angiogenesis. These findings support the potential of the MEL@EXO hydrogel as a robust and versatile platform for full-thickness wound healing.
To overcome the limitations of single-modality therapies, this study developed a smart, light-and pH-responsive polymeric nanotheranostic platform for synergistic chemo-photothermal treatment (CPTT) of murine breast cancer. In this regard, a novel amphiphilic folate-conjugated Pluronic F127-poly(beta-amino ester) copolymer was synthesized, providing an optimized hydrophilic-lipophilic balance (fEO = 27%) for self-assembly to vesicular architectures with a critical micelle concentration (CMC) of 25 mu g/mL. Using the thin-film hydration technique, the copolymer was converted into uniform, spherical, and dual-stimuli-responsive polymersomes co-loaded with DOX and ICG, exhibiting high colloidal stability and encapsulation efficiency (>95%). Folic acid (FA) functionalization enabled active targeting to folate receptor-overexpressing 4 T1 murine breast cancer cells, while near-infrared (NIR, 808 nm) irradiation of encapsulated ICG generated localized hyperthermia and facilitated NIR fluorescence imaging both in vitro and in vivo. The system demonstrated pH-dependent accelerated DOX release under acidic environment and light-triggered release upon NIR exposure. In vitro studies showed markedly greater cytotoxicity and cellular internalization with the dual chemo-PTT approach than with single-modality DOX-based chemotherapy. In vivo, intravenous injection of the FA-targeted DOX-ICG-loaded polymersomes followed by 808 nm laser irradiation resulted in complete and sustained tumor suppression in 4 T1 tumor-bearing mice, outperforming the non-irradiated formulation and free DOX. NIR imaging confirmed tumor-specific accumulation and diagnostic capability at 6 and 24 h post-administration, with ex vivo organ analysis supporting favorable biodistribution. These findings establish this multifunctional polymersome nanoplatform as a promising nanotheranostic agent for integrated imaging-guided synergistic CPTT in breast cancer, with potential for translation to refractory or aggressive subtypes.
EpCAM-targeted MoS 2 /MnO 2 /ICG nanoparticles enable GSH-responsive drug release, multimodal imaging, and laser-triggered photothermal/photodynamic therapy for breast cancer suppression.
Effective wound healing is often hindered by hypoxia, inflammation, and impaired angiogenesis. Although mesenchymal stem cell (MSC)-based therapies have shown potential, their clinical application remains limited. As a result, MSC-derived exosomes, particularly adipose-derived stem cell exosomes (ADSC-Exos), have been proposed as a cell-free alternative; however, they still face limitations, including suboptimal efficiency in targeted delivery. To address these critical obstacles in existing regenerative therapies, we isolated ADSC-Exos from adipose tissue and fabricated a novel ultrasound-responsive, carbomer-based hydrogel incorporating oxygen-enriched ADSC-Exo nanobubbles (Gel-Exo-NB+US). The preclinical wound-healing potential of the developed nanohydrogel was evaluated using a full-thickness wound model in Wistar rats. The engineered hydrogel exhibited favorable physicochemical properties, including shear-thinning and thixotropic behavior, enabling efficient topical application and enhanced tissue adhesion. In a rat full-thickness skin defect model, the combined Gel-Exo-NB and Gel-Exo-NB + US treatments achieved the highest wound-closure rate among all groups, with enhanced re-epithelialization, a reduced scar index, elevated CD31 and α-SMA expression, increased fibroblast proliferation, and increased blood vessel formation. Furthermore, unprecedented hair-follicle regeneration and abundant collagen deposition were observed in the Gel-Exo-NB + US-treated group compared with the Gel-Exo-NB-treated group, highlighting the pivotal role of ultrasound in skin defect regeneration. Notably, the resulting collagen deposition, abundant hair follicles, and thin epidermis suggest potential for scarless wound healing. These therapeutic outcomes are attributed to the synergistic effects of simultaneous ultrasound-mediated exosome therapy and oxygen delivery.
Bimetallic nanozymes integrated with aptamers have emerged as a promising platform in biosensing, combining the superior catalytic performance of dual-metal nanostructures with the exquisite molecular recognition of aptamers. The synergistic interplay between two metal components enhances catalytic efficiency, electron transfer, and structural stability beyond that of monometallic nanozymes. Coupled with aptamers, these systems enable rapid, accurate, and cost-effective detection of diverse analytes in complex matrices. This review delineates the fundamental catalytic mechanisms of bimetallic nanozymes alongside principles of aptamer-based target recognition. Key design considerations, including nanozyme composition, metal-organic framework engineering, aptamer selection and immobilization, and strategies for modulating catalytic activity, are critically examined. Diverse signal transduction modalities-colorimetric, fluorescence, electrochemical, and photoelectrochemical-are compared for sensitivity, selectivity, and practicality. The applications of these sensing systems are then summarized across antibiotics, toxins, disease biomarkers, cells, exosomes and microorganisms with emphasis on analytical performance in real samples. Persistent challenges, including limited biocompatibility, aptamer degradation, physiological instability, and fabrication complexity, are highlighted. Future directions emphasize dual-mode and multiplexed sensing, nuclease-resistant aptamer engineering, antifouling surface modifications, simplified assay formats, and rigorous large-scale validation. Collectively, this review provides a framework to guide the rational design and clinical translation of bimetallic nanozyme-aptamer biosensors.
Blocking the PD-1/PD-L1 (Programmed Cell Death Protein-1/Programmed Cell Death Ligand-1) pathway represents a pivotal approach in cancer immunotherapy, effectively promoting sustained antitumor immune responses while alleviating immunosuppressive mechanisms. Advancing novel technologies to enhance the efficacy of PD-1/PD-L1 blockade remains a critical focus in medical research. Nonetheless, challenges such as immune-related adverse effects, therapeutic resistance, and high treatment costs highlight the urgent need for innovative strategies that optimize clinical outcomes and accessibility. Aptamers are short, single-stranded oligonucleotides characterized by their high affinity and specificity for target molecules. Emerging as promising alternatives to traditional antibody-based therapies, they offer new avenues in cancer treatment. This review provides a comprehensive analysis of aptamer-driven strategies aimed at inhibiting the PD-1/PD-L1 immune checkpoint pathway. It summarizes recent advances in the design of PD-1/PD-L1-targeted aptamer systems and evaluates their potential to enhance therapeutic efficacy while addressing challenges related to immune resistance.
The poor cure rates and elevated mortality linked to cancers present a considerable threat to human health. The incorporation of diverse treatment modalities presents a hopeful method for combating cancer. In this research, a nanocomplex was engineered consisting of pH-responsive carbon dot (PCD) conjugated with the AS1411 aptamer, encapsulated within red blood cell membrane (RBCM)-coated Hollow Gold nanoparticle (HAu), and loaded with mitoxantrone (MTO). This system is designed to react specifically to the tumor microenvironment, enabling synergistic photothermal and chemotherapeutic treatment for cancer. The findings from fluorescence imaging indicated that the nanocomplex is capable of effectively concentrating in tumor locations. Within the acidic microenvironment of tumors, PCDs-Apt-RBCM-HAu released MTO, thereby initiating chemotherapy to eliminate tumor cells. Additionally, when subjected to an 808 nm laser, the pH-sensitive nanocomplexes exhibited a photothermal effect, facilitating an efficient hyperthermia treatment for colon cancer. These nanocomplexes are characterized by simple synthesis, low toxicity, regulated drug release, and imaging-assisted treatment, emphasizing their promise for accurate and effective combination therapies within biomedical fields.
Introduction: Ureteral stents are widely used in various urological procedures; however, they are frequently associated with bothersome symptoms that affect patient quality of life. This study aimed to evaluate the additive effect of gabapentin combined with solifenacin in controlling stent-associated symptoms following double-J stent placement after ureteroscopic lithotripsy. Methods: This prospective randomized controlled trial was conducted between 2019 and 2021 at a tertiary referral center. Adult patients who underwent ureteroscopic lithotripsy for unilateral ureteral stones with subsequent double-J stent placement were included. A total of 160 patients were randomized into two groups. The intervention group received gabapentin 100 mg plus solifenacin 5 mg daily, whereas the control group received Solifenacin 5 mg daily plus placebo for 2 weeks. Symptom severity was evaluated using the Ureteral Stent Symptom Questionnaire (USSQ) 2 weeks postoperatively. Results: The mean total USSQ score was significantly lower in the intervention group (75.17 ± 13.90) compared to the control group (87.98 ± 17.44; P < 0.001). In addition, the intervention group demonstrated significant improvements in urinary symptoms, pain, general health, work performance, and other domains (P < 0.05 for all). Conclusions: Gabapentin appears to be a safe and effective adjunct for reducing symptoms associated with ureteral stent placement, particularly reducing pain and improving general health status. Its combination with solifenacin may offer enhanced symptom control and better patient-reported outcomes.
Ferroptosis is a programmed cell death, distinct from all types of cell killing, including apoptosis, and can be activated in many pathological conditions. Thus, ferroptosis has been considered as a potential treatment for cancer. Iron, an essential element for all living cells, plays a vital role at the beginning of ferroptosis. Two forms of iron in the cells are Fe2+ and Fe3+, where Fe 2+ has susceptibility for electron transfer and performs a central role in oxidation-reduction reactions. Hydroxyl radicals in reactive oxygen species (ROS) could be generated via the Fenton reaction between ferrous (Fe2+) iron (electron transfer) and H2O2, and consequently promote ferroptosis in cells. Combining nanotechnology with ferroptosis could offer an innovative strategy for cancer treatment. In recent decades, nanoplatforms have revolutionized drug delivery systems and their applications in the diagnosis and treatment of cancer. In this regard, ferroptosis-inducing nanoplatforms, such as inorganic nanomaterials, have been extensively implemented. This review provides an updated summary of studies on the advantages of iron-based nanomaterials for inducing ferroptosis in cancer treatment. Furthermore, we summarized the various reports on nanoplatforms co-loaded with iron and therapeutic agents for synergistic therapy.
Lung cancer represents a prevalent factor in cancer-associated deaths globally, and its prompt identification serves as a means to enhance the survival rates of individuals afflicted by this illness. Hence, timely and efficient detection of non-small cell lung cancer (NSCLC) at premalignant stages necessitates the search for new therapeutic targets or improvement of reliable and early-detection methods. In the present study, a sensitive fluorescent rolling circle amplification (RCA)-based approach was proposed for the identification of A549 cells in human serum samples. In this design, the aptamer plays the role of a primer to guide the RCA process and complementary strand (CS) acts as a locker. This method can detect A549 cancer cells in the range of 102-5 x 105 cell mL(- 1) and the detection limit is 28 cell mL(- 1) under optimal conditions. The results show that our current approach is simpler and more cost-effective than existing traditional detection methods and shows promising prospect in the fields of diagnosis and treatment.
Manganese-based metal–organic frameworks (Mn MOFs) represent a highly promising class of materials, characterized by their low toxicity, oxidative capabilities, and biocompatibility, which render them particularly advantageous for various biomedical applications. This study presents the development of a biodegradable, intelligent carrier utilizing MOFs with Mn center and 4,4'-dithiobisbenzoic acid ligands that responds to pH changes and glutathione levels for targeted chemodynamic therapy. The synthesized nanoparticles demonstrated remarkable encapsulation efficiency and a doxorubicin hydrochloride (DOX) loading capacity of 84.95 ± 1.7
In the current study, a nanoscale metal-organic framework (MOF), FeP-Zr MOF, was synthesized with a Zr4+ metal core and Fe-porphyrin as connector ligands. Fe-porphyrin offers the MOFs a potent T1/T2-weighted magnetic resonance imaging (MRI) contrast for monitoring and high photothermal conversion for photothermal therapy (PTT). The highlight is that Zr metal nodes in the MOF structure could act as computed tomography (CT) imaging contrast agents. On the other hand, the porous structure of the MOF was utilized as a reservoir for loading doxorubicin (DOX). Then, the DOX-loaded MOF was surface-modified with dextran (DEX) and a linear cysteine-extended RGD peptide (cys-RGD) to improve biocompatibility and the therapeutic index against melanoma. The prepared platform showed a favorable conversion of 808 nm laser irradiation into heat. An in vitro study on B16F0 cells confirmed the targeted delivery of DOX to cancerous cells and also demonstrated the synergistic effect of 808 nm laser irradiation and DOX exposure on cellular toxicity. In the preclinical stage, after intravenous injection of the prepared platform into subcutaneous B16F0-tumor-bearing mice, it demonstrated efficient tumor accumulation, as visualized by MR and CT images. Furthermore, mice treated with DOX@FeP-Zr/DEX/RGD, along with 808 nm laser irradiation, showed 100 % tumor suppression. The current investigation introduces an innovative multipurpose platform for synergistic chemo-photothermal therapy (CPTT) of melanoma, offering dual-modal CT/MR imaging capabilities.
Elevated concentrations of sulfadimethoxine (SDM) in food products contribute to the development of bacterial resistance, resulting in a range of health problems for individuals. This background makes it incumbent to develop an efficient and accurate detection method for SDM. Rolling circle amplification (RCA) is an easy operation and highly efficient signal improvement technique that does not require thermal cycling. This study presents a fluorescent aptasensor that operates without labels to detect SDM, utilizing the RCA process. Using the RCA method as the main contributor for signal amplification, a large number of DNA copies is produced in a short time. This allows for the immobilization of SYBR Green (SGI) molecules and a sharp increase in the fluorescence response. Hence, it can be achieved a wide detection range of SDM from 1 pM to 200 nM and an impressive detection limit of 0.238 pM. The aptasensor can successfully monitor SDM in various livestock products and biological samples. This aptasensor offers advantages such as a short fabrication time, cost-effectiveness, and user-friendliness. It can be promoted as a convenient and economic portable testing kit.
The transdermal route of drug delivery is convenient and pain-free, and allows a controlled release pattern. However, many therapeutically active drugs cannot bypass the stratum corneum effectively. Lipophilic drugs, like nifedipine, cross the outer skin barrier easily, while hydrophobic drugs, such as insulin, are ineffective in showing the same effect. Due to these reasons, advancements in drug delivery have received much attention to deliver a wide range of drugs, especially macromolecules, through the transdermal route and directly into the systemic circulation via bypassing hepatic metabolism and gastrointestinal degradation. So, there is a need for advanced drug delivery systems, like microneedles and nanoneedles, through the transdermal route. These tiny needles will also serve as non-toxic, safe, and stable systems for advanced drug delivery. Thus, micro-to nano-formulations are the fast-emerging fields of transdermal delivery, which have additional advantages over transdermal patches, such as better penetration, permeation, controlled release, and direct delivery to the cytoplasm. The current review discusses the recent advancements in insulin delivery by micro- and nano-needles to gain a better practical insight for diabetic patients.