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OBJECTIVE: This study aimed to illustrate the copper status of diminished ovarian reserve in Chinese women, especially the effects of copper, ceruloplasmin, non-ceruloplasmin-bound copper (NCC) and CuZn superoxide dismutase (SOD1). METHODS: This case-control, cross-sectional investigation included women with diminished ovarian reserve (DOR group, n = 35) and matched normal ovarian reserve (NOR group, n = 35). The serum levels of copper, ceruloplasmin, NCC, SOD1, follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, and anti-Müllerian hormone were tested and analyzed. RESULTS: The serum copper concentrations (60.88%), NCC (54.75%) and SOD1 (54.75%) in the DOR group were significantly higher than those in the NOR group (all P < 0.001), and the concentrations of the three markers were higher in most subgroups (P < 0.001). The correlation analysis verified the correlation between copper status and impaired ovarian function. Additionally, linear regression analysis showed that NCC and SOD1 levels were negatively correlated with anti-Müllerian hormone (P < 0.05 or 0.001). CONCLUSION: Our exploration found significant increases in copper, NCC and SOD1 levels in DOR and suggests a possible link. Copper status is expected to serve as the predictive marker for DOR.
ABSTRACT
Using the linear approach to design a controller is still prevalent. The state feedback control (SFC) is applied in this paper to improve the dynamic response of permanent magnet synchronous machine (PMSM) speed regulation systems. First, a third-order augmented system is constructed for the reason that a higher-order system has better disturbance rejection. It can be found through analysis and comparison that the order of the proposed speed controller is increased. The parameters of SFC are selected by utilizing the linear quadratic regulator (LQR), and the influence of matrix Q on dynamic performance is detailed through the Bode diagram. Additionally, considering parametric uncertainties and unmodeled dynamics, a disturbance observer (DOB) using the Luenberger observer is designed to further boost anti-disturbance performance. Finally, plenty of experimental results verify the effectiveness of the proposed methods.
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This study aimed to better understand whether and how the reactive 1,2-dicarbonyl precursors of advanced glycation end products (AGEs), glyoxal (GO) and methylglyoxal (MGO), cross the intestinal barrier by studying their transport in the in vitro Caco-2 transwell system. The results reveal that GO, MGO and Nε-(carboxymethyl)lysine (CML), the latter studied for comparison, are transported across the intestinal cell layer via both active and passive transport and accumulate in the cells, albeit all to a limited extent. Besides, the transport of the dicarbonyl compounds was only partially affected by the presence of amino acids and protein, suggesting that scavenging by a food matrix will not fully prevent their intestinal absorption. Our study provides new insights into the absorption of the two major food-borne dicarbonyl AGE precursors and provides evidence of their potential systemic bioavailability but also of factors limiting their contribution to the overall exposome.
Subject(s)
Glycation End Products, Advanced , Glyoxal , Pyruvaldehyde , Humans , Caco-2 Cells , Glycation End Products, Advanced/metabolism , Glycation End Products, Advanced/chemistry , Pyruvaldehyde/metabolism , Glyoxal/metabolism , Glyoxal/chemistry , Models, Biological , Biological Transport , Intestinal AbsorptionABSTRACT
Soil salinization leads to a reduction in arable land area, which seriously endangers food security. Developing saline-alkali land has become a key measure to address the contradiction between population growth and limited arable land. Rice is the most important global food crop, feeding half of the world's population and making it a suitable choice for planting on saline-alkali lands. The traditional salt-alkali improvement method has several drawbacks. Currently, non-thermal plasma (NTP) technology is being increasingly applied in agriculture. However, there are few reports on the cultivation of salt/alkali-tolerant rice. Under alkaline stress, argon NTP treatment significantly increased the germination rate of Longdao 5 (LD5) rice seeds. In addition, at 15 kV and 120 s, NTP treatment significantly increased the activity of antioxidant enzymes such as catalase and SOD. NTP treatment induced changes in genes related to salt-alkali stress in rice seedlings, such as chitinase and xylanase inhibitor proteins, which increased the tolerance of the seeds to salt-alkali stress. This experiment has expanded the application scope of NTP in agriculture, providing a more cost-effective, less harmful, and faster method for developing salt-alkali-tolerant rice and laying a theoretical foundation for cultivating NTP-enhanced salt-alkali-tolerant rice.
Subject(s)
Alkalies , Argon , Oryza , Plasma Gases , Oryza/growth & development , Oryza/drug effects , Plasma Gases/pharmacology , Alkalies/chemistry , Argon/pharmacology , Argon/chemistry , Germination/drug effects , Seedlings/drug effects , Seedlings/growth & development , Seeds/drug effects , Seeds/growth & developmentABSTRACT
The aryl hydrocarbon receptor (AHR) has been identified as a significant driver of tumorigenesis. However, its clinical significance in acute myeloid leukemia (AML) remains largely unclear. In this study, RNA-Seq data from AML patients (bone marrow samples from 173 newly diagnosed AML patients) obtained from the TCGA database, and normal human RNA-Seq data (bone marrow samples from 70 healthy individuals) obtained from the GTEX database are downloaded for external validation and complementarity. The data analysis reveals that the AHR signaling pathway is activated in AML patients. Furthermore, there is a correlation between the expressions of AHR and mitochondrial oxidative phosphorylation genes. In vitro experiments show that enhancing AHR expression in AML cells increases mitochondrial oxidative phosphorylation and induces resistance to cytarabine. Conversely, reducing AHR expression in AML cells decreases cytarabine resistance. These findings deepen our understanding of the AHR signaling pathway's involvement in AML.
Subject(s)
Cytarabine , Leukemia, Myeloid, Acute , Humans , Cytarabine/pharmacology , Oxidative Phosphorylation , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism , Signal Transduction , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolismABSTRACT
This paper proposes a composite sliding mode control (SMC) to optimize the tracking performance and the anti-disturbance performance of permanent magnet synchronous machine (PMSM) speed regulation systems. The differential term in the control law can magnify the measurement noise, resulting in more discontinuity. To filter out the high frequency noise and make the control law smoother, the first-order differentiator (FOD) is employed to estimate the speed error and its derivative. Since the feedforward compensation can improve the robustness of the system, a disturbance observer (DOB) based on the sliding mode observer (SMO) is designed to reinforce the dynamic performance under disturbance variation. Under the effect of the feedforward compensation, chattering can be further weakened by decreasing the switching gain appropriately. Finally, the effectiveness of the proposed methods is confirmed by various experimental results.
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This study aimed to identify risk and protective factors for suicidal tendencies among college students by exploring current mental health, personal experiences, family environment, and school adaptation. A total of 11,504 freshmen in China were recruited. Suicidal tendencies were assessed using the Adolescents Suicidal Tendencies Scale (ASTS), while explored risk and protective factors included mental health assessed by the Symptom Checklist-90 (SCL-90), campus adaptation using the College Student School Adaptation Scale, and Personal Situation Survey. Single-factor Logistic regression analysis, correlation analysis, and hierarchical regression analysis were used to analyze the risk and protective factors affecting suicidal tendencies. The results showed that in terms of personal experience, self-injury behavior (OR = 3.522, 95% CI [3.256, 3.811]), sexual assault experience (OR = 2.603, 95% CI [2.374, 2.855]) and lack of friendship relationship (OR = 2.249, 95% CI [2.076, 2.436]) were the most significant risk factors. Regarding family environment, parenting style (OR = 2.455, 95% CI [2.272, 2.652]), parent-child relationship (OR = 2.255, 95% CI [2.092, 2.429]) and violent conflict (OR = 2.164, 95% CI [2.015, 2.324]) were the most prominent risk factors. For protective factors, life satisfaction (OR = 0.330, 95% CI [0.304, 0.359]) and rest quality (OR = 0.415, 95% CI [0.386, 0.447]) were the most significant protective factors. In addition, Symptom Checklist-90 was positively correlated with suicidal tendencies (r = 0.541, 95% CI [0.522, 0.560], p < 0.001), while school adaptation was negatively correlated with suicidal tendencies (r = - 0.590, 95% CI [- 0.579, - 0.601], p < 0.001). After considering demographic variables, psychological symptoms, school adaptation and other risk and protective factors, the hierarchical regression model could explain 48.9% of the variance of suicidal tendencies. The study emphasizes a range of multidimensional risk and protective factors for suicidal tendencies. This enhanced understanding is crucial in aiding the design of future intervention studies targeted at improving the mental health of college students.
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Previously, Lactobacillus paracasei VL8, a lactobacillus strain isolated from the traditional Finnish fermented dairy product Viili, demonstrated immunomodulatory and antibacterial effects. The prebiotic mannan-oligosaccharide (MOS) further promoted its antibacterial activity and growth performance, holding promise for maintaining intestinal health. However, this has not been verified in vivo. In this study, we elucidated the process by which L. paracasei VL8 and its synbiotc combination (SYN) with MOS repair the intestinal barrier function in dextran sodium sulfate (DSS)-induced colitis mice. SYN surpasses VL8 or MOS alone in restoring goblet cells and improving the tight junction structure. Omics analysis on gut microbiota reveals SYN's ability to restore Lactobacillus spp. abundance and promote tryptophan metabolism. SYN intervention also inhibits the DSS-induced hyperactivation of the Wnt/ß-catenin pathway. Tryptophan metabolites from Lactobacillus induce intestinal organoid differentiation. Co-housing experiments confirm microbiota transferability, replicating intestinal barrier repair. In conclusion, our study highlights the potential therapeutic efficacy of the synbiotic combination of Lactobacillus paracasei VL8 and MOS in restoring the damaged intestinal barrier and offers new insights into the complex crosstalk between the gut microbiota and intestinal stem cells.
Subject(s)
Colitis , Lacticaseibacillus paracasei , Probiotics , Synbiotics , Animals , Mice , Dextran Sulfate/adverse effects , Mannans , Probiotics/pharmacology , Stem Cell Niche , Tryptophan , Colitis/chemically induced , Colitis/genetics , Colitis/therapy , Lactobacillus , Oligosaccharides , Anti-Bacterial Agents/adverse effects , Disease Models, Animal , Mice, Inbred C57BL , ColonABSTRACT
Photocatalytic oxidative coupling of methane (OCM) into value-added industrial chemicals offers an appealing green technique for achieving sustainable development, whereas it encounters double bottlenecks in relatively low methane conversion rate and severe overoxidation. Herein, we engineer a continuous gas flow system to achieve efficient photocatalytic OCM while suppressing overoxidation by synergizing the moderate active oxygen species, surface plasmon-mediated polarization, and multipoint gas intake flow reactor. Particularly, a remarkable CH4 conversion rate of 218.2 µmol h-1 with an excellent selectivity of â¼90% toward C2+ hydrocarbons and a remarkable stability over 240 h is achieved over a designed Au/TiO2 photocatalyst in our continuous gas flow system with a homemade three-dimensional (3D) printed flow reactor. This work provides an informative concept to engineer a high-performance flow system for photocatalytic OCM by synergizing the design of the reactor and photocatalyst to synchronously regulate the mass transfer, activation of reactants, and inhibition of overoxidation.
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BACKGROUND: Increasing evidence indicate that enhanced adipogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) could contribute to the adiposity alteration in marrow microenvironment of aplastic anemia (AA). Identifying small molecule drugs with role in inhibiting adipogenesis of BM-MSCs may represent a novel direction in AA therapy by improving BM-MSCs mediated marrow microenvironment. METHODS: For the purpose, we isolated AA BM-MSCs through whole bone marrow cell culture, evaluated a series of small molecule drugs using the in vitro adipogenic differentiation model of BM-MSCs, and finally focused on emodin, a natural anthraquinone derivative. Subsequently, we systematically investigated the molecular mechanism of emodin in attenuating adipogenic process by means of microarray profiling, bioinformatics analysis and lentivirus-mediated functional studies and rescue assay. RESULTS: We found that emodin presented significantly suppressive effect on the in vitro adipogenic differentiation of AA BM-MSCs. Further mechanistic investigation revealed that emodin could increase the expression of Tribbles homolog 3 (TRIB3) which exhibited remarkably decreased expression in AA BM-MSCs compared with the normal counterparts and was subsequently demonstrated as a negative regulator in adipogenesis of AA BM-MSCs. Besides, TRIB3 depletion alleviated the suppressive effect of emodin on the adipogenic differentiation of AA BM-MSCs. CONCLUSION: Our findings propose that emodin mediated TRIB3 up-regulation alleviates the adipogenic capacity of AA BM-MSCs, and emodin could serve as a potential therapeutic regimen for AA therapy.
Subject(s)
Anemia, Aplastic , Emodin , Mesenchymal Stem Cells , Humans , Adipogenesis/genetics , Anemia, Aplastic/drug therapy , Anemia, Aplastic/metabolism , Bone Marrow , Emodin/pharmacology , Bone Marrow Cells , Cell Differentiation , Cells, Cultured , Repressor Proteins/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Cell Cycle Proteins/metabolismABSTRACT
Misuse of opioids can lead to a potential lethal overdose. Timely administration of naloxone is critical for survival. Here, we designed a polymer-naloxone conjugate that can provide on-demand phototriggered opioid reversal. Naloxone was attached to the polymer poly(lactic-co-glycolic acid) via a photocleavable coumarin linkage and formulated as injectable nanoparticles. In the absence of irradiation, the formulation did not release naloxone. Upon irradiation with blue (400 nm) light, the nanoparticles released free naloxone, reversing the effect of morphine in mice. Such triggered events could be performed days and weeks after the initial administration of the nanoparticles and could be performed repeatedly.
Subject(s)
Drug Overdose , Naloxone , Mice , Animals , Naloxone/pharmacology , Naloxone/therapeutic use , Analgesics, Opioid/therapeutic use , Narcotic Antagonists/therapeutic use , Polymers/pharmacology , Polymers/therapeutic use , Drug Overdose/drug therapyABSTRACT
Generative artificial intelligence has depicted a beautiful blueprint for on-demand design in chemical research. However, the few successful chemical generations have only been able to implement a few special property values because most chemical descriptors are mathematically discrete or discontinuously adjustable. Herein, we use spectroscopic descriptors with machine learning to establish a quantitative spectral structure-property relationship for adsorbed molecules on metal monatomic catalysts. Besides catalytic properties such as adsorption energy and charge transfer, the complete spatial relative coordinates of the adsorbed molecule were successfully inverted. The spectroscopic descriptors and prediction models are generalized, allowing them to be transferred to several different systems. Due to the continuous tunability of the spectroscopic descriptors, the design of catalytic structures with continuous adsorption states generated by AI in the catalytic process has been achieved. This work paves the way for using spectroscopy to enable real-time monitoring of the catalytic process and continuous customization of catalytic performance, which will lead to profound changes in catalytic research.
ABSTRACT
Insufficient drug loading and leakage of payload remain major challenges in designing liposome-based drug delivery systems. These phenomena can limit duration of effect and cause toxicity. Targeting the rate-limiting step in drug release from liposomes, we modify (aromatized) them to have aromatic groups within their lipid bilayers. Aromatized liposomes are designed with synthetic phospholipids with aromatic groups covalently conjugated onto acyl chains. The optimized aromatized liposome increases drug loading and significantly decreases the burst release of a broad range of payloads (small molecules and macromolecules, different degrees of hydrophilicity) and extends their duration of release. Aromatized liposomes encapsulating the anesthetic tetrodotoxin (TTX) achieve markedly prolonged effect and decreased toxicity in an application where liposomes are used clinically: local anesthesia, even though TTX is a hydrophilic small molecule which is typically difficult to encapsulate. Aromatization of lipid bilayers can improve the performance of liposomal drug delivery systems.
Subject(s)
Lipid Bilayers , Liposomes , Drug Delivery Systems , Phospholipids , Drug LiberationABSTRACT
Hydrogen isotope separation is of prime significance in various scientific and industrial applications. Nevertheless, the existing technologies are often expensive and energy demanding. Two-dimensional carbon materials are regarded as promising candidates for cost-effective separation of different hydrogen isotopes. Herein, based on theoretical calculations, we have systematically investigated the proton penetration mechanism and the associated isotope separation behavior through two-dimensional biphenylene, a novel graphene allotrope. The unique non-uniform rings with different sizes in the biphenylene layer resemble the topological defects of graphene, serving as proton transmission channels. We found that a proton can readily pass through biphenylene with a low energy barrier in some specific patterns. Furthermore, large kinetic isotope effect ratios for proton-deuteron (13.58) and proton-triton (53.10) were observed in an aqueous environment. We thus conclude that biphenylene would be a potential carbon material used for hydrogen isotope separation. This subtle exploitation of the natural structural specificity of biphenylene provides new insight into the search for materials for hydrogen isotope separation.
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OBJECTIVES: Orthostatic hypotension (OH) is one of the most important autonomic features of multiple system atrophy (MSA). This study was established to confirm the correlation between lipid levels and OH in MSA. METHODS: A total of 580 patients with probable or possible MSA from neurological wards in six hospitals in Tianjin, Beijing, Hebei Province, and Henan Province, China, were included in this study. The tilt test or stand test was used to assess the severity of OH. Lipid contents, including total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglyceride were evaluated. RESULTS: Serum levels of total cholesterol, LDL-C, and triglyceride in MSA-OH patients were significantly lower than those in MSA without OH. The risks of OH were significantly higher in the lowest quartiles of triglyceride and LDL-C than in the highest quartiles, after adjusting for confounders (OR = 2.17, 95% CI: 1.23-3.82, P = 0.008 and OR = 2.02, 95% CI: 1.16-3.47, P = 0.012). The risk of severe OH was significantly higher in the lowest quartile and the second quartile of triglyceride than in the highest quartile after adjusting for confounders (OR = 2.16, 95% CI: 1.20-3.87, P = 0.010 and OR = 2.25, 95% CI: 1.24-4.07, P = 0.007). Moreover, the risk of OH was significantly higher in the lowest quartile, and the third quartile of TC than in the highest quartile after adjusting for confounders (OR = 2.04, 95% CI: 1.18-3.52, P = 0.010 and OR = 2.06, 95% CI: 1.19-3.56, P = 0.010). CONCLUSION: Low levels of TC, LDL-C, and triglyceride increased the risk of OH in MSA. A low level of triglyceride predicted severe OH in MSA.
Subject(s)
Hypotension, Orthostatic , Multiple System Atrophy , Humans , Multiple System Atrophy/complications , Hypotension, Orthostatic/complications , Cholesterol, LDL , Triglycerides , Cholesterol, HDLABSTRACT
Thermoresponsive polymers that undergo sol-gel transitions in the physiological temperature range have been widely used in biomedical applications. However, some commercially and clinically available thermoresponsive materials, particularly poloxamer 407 (P407), have the significant drawback of insufficient gel strength, which limit their performance. Furthermore, co-delivery with some small molecules, including chemical permeation enhancers (CPEs) can further impair the physical properties of P407. Here, we have developed a thermoresponsive platform by combination of CPEs with the poloxamer P188 to enable gelation at physiological temperatures and enhance gel strength. P188 gels at 60 °C, which is far above the physiological range. In combination with limonene (LIM) and sodium dodecyl sulfate (SDS), P188 gels at â¼25 °C, a temperature that in useful for biomedical applications. Gelation behavior was studied by small angle neutron scattering (SANS) experiments, which identified micelle-to-cubic mesophase transitions with increasing temperature. Analysis of the SANS intensities revealed that P188 micelles became larger as LIM or SDS molecules were incorporated, making it easier to form a micellar gel structure. P188-3CPE (i.e., 2% LIM, 1% SDS and 0.5% bupivacaine (BUP)) had low viscosity at room temperature, facilitating administration, but rapidly gelled at body temperature. P188-3CPE enabled the flux of the antibiotic ciprofloxacin across the TM and completely eradicated otitis media from nontypable Haemophilus influenzae (NTHi) in chinchillas after a single administration.
ABSTRACT
Mild cognitive impairment (MCI) in multiple-system atrophy (MSA) patients is common but remains poorly characterized, and the related factors are unclear. This retrospective study included 200 consecutive patients with a clinical diagnosis of possible or probable MSA, 102 MSA patients with MCI (MSA-MCI), and 98 MSA patients with normal cognition (MSA-NC). Cognitive profiles were compared between MSA-MCI and MSA-NC patients using the MoCA. In addition, demographic as well as major motor and nonmotor symptom differences were compared between MSA-MCI and MSA-NC patients. The median MMSE score was 26 points. Overall, MSA-MCI was observed in 51% of patients, with predominant impairment in visuospatial, executive, and attention functions compared with MSA-NC patients. MSA-MCI patients were older (p = 0.015) and had a later onset age (p = 0.024) and a higher frequency of hypertension, motor onset, and MSA with the predominant parkinsonism (MSA-P) phenotype than MSA-NC patients. The positive rate of orthostatic hypotension (OH) in MSA-MCI patients was significantly decreased and depression/anxiety was significantly increased compared with MSA-NC patients (p = 0.004). Multivariate logistic analysis showed that motor onset was independently associated with MCI in MSA patients. MSA-MCI patients had impairment in visuospatial, executive, and attention functions. More prominent memory impairment was observed in MSA-P than in MSA-C patients. Motor onset was independently associated with MCI in MSA patients. MCI was commonly presented in MSA with more prominent memory impairment in MSA-P. Future follow-up studies are warranted to identify more factors that influence cognitive impairment in MSA.
ABSTRACT
Electrochemical oxygen reduction reaction (ORR) is fundamental for many energy conversion and storage devices. Selective tuning of *OOH/*OH adsorption energy to break the intrinsic scaling limitation (ΔG*OOH =ΔG*OH +3.2â eV) is effective in optimizing the ORR limiting potential (UL ), which is practically challenging to achieve by constructing a particular catalyst. Herein, using first-principles calculations, we elucidated how to rationally plant an additional *OH that can selectively interact with the ORR intermediate of *OOH via hydrogen bonding, while not affecting the *OH intermediate. Guided by the design principle, we successfully tailored a series of novel carbon-based catalysts, with merits of low-cost, long-lasting, synthesis feasibility, exhibiting a high UL (1.06â V). Our proposed strategy comes up with a new linear scaling relationship of ΔG*OOH =ΔG*OH +2.84â eV. This approach offers a great possibility for the rational design of efficient catalysts for ORR and other chemical reactions.
ABSTRACT
Designing a novel nanoplatform that integrates multimodal imaging and synergistic therapy for precision tumor nanomedicines is challenging. Herein, we prepared rare-earth ion-doped upconversion hydroxyapatite (FYH) nanoparticles as nanocarriers coated and loaded respectively with polydopamine (PDA) and doxorubicin (DOX), i.e., FYH-PDA-DOX, for tumor theranostics. The developed FYH-PDA-DOX complexes exhibited desirable photothermal conversion, pH/near-infrared-irradiation-responsive DOX release, and multimodal upconversion luminescence/computed tomography/magnetic resonance imaging performance and helped monitor the metabolic distribution process of the complexes and provided feedback to the therapeutic effect. Upon 808 nm laser irradiation, the fast release of DOX facilitated the photothermal-chemotherapy effect, immunogenic cell death, and antitumor immune response. On combining with the anti-programmed cell death 1 ligand 1 antibody, an enhanced tri-mode photothermal-chemo-immunotherapy synergistic treatment against tumors can be realized. Thus, this treatment elicited potent antitumor immunity, producing appreciable T-cell cytotoxicity against tumors, amplifying tumor suppression, and extending the survival of mice. Therefore, the FYH-PDA-DOX complexes are promising as a smart nanoplatform for imaging-guided synergistic cancer treatment.
Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Animals , Mice , Hyperthermia, Induced/methods , Doxorubicin/therapeutic use , Neoplasms/therapy , Neoplasms/drug therapy , Phototherapy/methods , Immunotherapy , Multimodal Imaging , Cell Line, TumorABSTRACT
Delivery of hydrophilic small molecule therapeutics by traditional drug delivery systems is challenging. Herein, we have used the specific interaction between DNA aptamers and drugs to create simple and effective drug depot systems. The specific binding of a phosphorothioate-modified aptamer to drugs formed non-covalent aptamer/drug complexes, which created a sustained release system. We demonstrated the effectiveness of this system with small hydrophilic molecules, the site 1 sodium channel blockers tetrodotoxin and saxitoxin. The aptamer-based delivery system greatly prolonged the duration of local anesthesia and reduced systemic toxicity. The beneficial effects of the aptamers were restricted to the compounds they were specific to. These studies establish aptamers as a class of highly specific, modifiable drug delivery systems, and demonstrate potential usefulness in the management of postoperative pain.