High-performance and low-power source-gated transistors enabled by a solution-processed metal oxide homojunction.

Cost-effective fabrication of mechanically flexible low-power electronics is important for emerging applications including wearable electronics, artificial intelligence, and the Internet of Things. Here, solution-processed source-gated transistors (SGTs) with an unprecedented intrinsic gain of ~2,000, low saturation voltage of +0.8 ± 0.1 V, and a ~25.6 µW power consumption are realized using an indium oxide In2O3/In2O3:polyethylenimine (PEI) blend homojunction with Au contacts on Si/SiO2. Kelvin probe force microscopy confirms source-controlled operation of the SGT and reveals that PEI doping leads to more effective depletion of the reverse-biased Schottky contact source region. Furthermore, using a fluoride-doped AlOx gate dielectric, rigid (on a Si substrate) and flexible (on a polyimide substrate) SGTs were fabricated. These devices exhibit a low driving voltage of +2 V and power consumption of ~11.5 µW, yielding inverters with an outstanding voltage gain of >5,000. Furthermore, electrooculographic (EOG) signal monitoring can now be demonstrated using an SGT inverter, where a ~1.0 mV EOG signal is amplified to over 300 mV, indicating significant potential for applications in wearable medical sensing and human-computer interfacing.

Flexible and Stretchable Enzymatic Biofuel Cell with High Performance Enabled by Textile Electrodes and Polymer Hydrogel Electrolyte.

Biofuel cells with good biocompatibility are promising to be used as the power source for flexible and wearable bioelectronics. We here report a type of highly flexible and stretchable biofuel cells, which are enabled by textile electrodes of graphene/carbon nanotubes (G/CNTs) composite and polymer hydrogel electrolyte. The CNT array covalently grown from a graphene layer not only can be served as a conducting substrate to immobilize enzyme molecules but also can provide efficient charge transport channels between the enzyme and graphene electrode. As a result, the developed biofuel cells deliver a high open-circuit voltage of 0.65 V and output power density of 64.2 µW cm-2, which are much higher than previously reported results. Benefiting from the unique textile structure of electrodes and the polymer hydrogel electrolyte, the biofuel cells exhibit high retention of power density after 400 bending cycles and even stretched to a high strain of 60%.

[Study on Factors Affecting Hemolytic Properties of Cyanoacrylate Glues for Surgical Use].

This study aims to discuss the factors affecting the hemolytic properties of α-cyanoacrylate glues for surgical use. The results showed that the different extractions, test methods, pH value, rapid solidification and the extract ratio were the main factors affecting the hemolytic properties. The choose of PBS as the extraction for haemolysis test maybe was more suitable than physiological saline. It was recommended that using both direct contact methods and indirect contact methods should be more comprehensive for hemolytic evaluation.

Novel approaches for periodontal tissue engineering.

The periodontal complex involves the hard and soft tissues which support dentition, comprised of cementum, bone, and the periodontal ligament (PDL). Periodontitis, a prevalent infectious disease of the periodontium, threatens the integrity of these tissues and causes irreversible damage. Periodontal therapy aims to repair and ultimately regenerate these tissues toward preserving native dentition and improving the physiologic integration of dental implants. The PDL contains multipotent stem cells, which have a robust capacity to differentiate into various types of cells to form the PDL, cementum, and alveolar bone. Selection of appropriate growth factors and biomaterial matrices to facilitate periodontal regeneration are critical to recapitulate the physiologic organization and function of the periodontal complex. Herein, we discuss the current state of clinical periodontal regeneration including a review of FDA-approved growth factors. We will highlight advances in preclinical research toward identifying additional growth factors capable of robust repair and biomaterial matrices to augment regeneration similarly and synergistically, ultimately improving periodontal regeneration's predictability and long-term efficacy. This review should improve the readers' understanding of the molecular and cellular processes involving periodontal regeneration essential for designing comprehensive therapeutic approaches.

Sequence-Reversible Construction of Oxygen-Rich Block Copolymers from Epoxide Mixtures by Organoboron Catalysts.

Switchable catalysis, in combination with epoxide-involved ring-opening (co)polymerization, is a powerful technique that can be used to synthesize various oxygen-rich block copolymers. Despite intense research in this field, the sequence-controlled polymerization from epoxide congeners has never been realized due to their similar ring-strain which exerts a decisive influence on the reaction process. Recently, quaternary ammonium (or phosphonium)-containing bifunctional organoboron catalysts have been developed by our group, showing high efficiency for various epoxide conversions. Herein, we, for the first time, report an operationally simple pathway to access well-defined polyether-block-polycarbonate copolymers from mixtures of epoxides by switchable catalysis, which was enabled through thermodynamically and kinetically preferential ring-opening of terminal epoxides or internal epoxides under different atmospheres (CO2 or N2) using one representative bifunctional organoboron catalyst. This strategy shows a broad substrate scope as it is suitable for various combinations of terminal epoxides and internal epoxides, delivering corresponding well-defined block copolymers. NMR, MALDI-TOF, and gel permeation chromatography analyses confirmed the successful construction of polyether-block-polycarbonate copolymers. Kinetic studies and density functional theory calculations elucidate the reversible selectivity between different epoxides in the presence/absence of CO2. Moreover, by replacing comonomer CO2 with cyclic anhydride, the well-defined polyether-block-polyester copolymers can also be synthesized. This work provides a rare example of sequence-controlled polymerization from epoxide mixtures, broadening the arsenal of switchable catalysis that can produce oxygen-rich polymers in a controlled manner.

Brefeldin A delivery nanomicelles in hepatocellular carcinoma therapy: Characterization, cytotoxic evaluation in vitro, and antitumor efficiency in vivo.

Hepatocellular carcinoma (HCC) is one of the major cancers with high mortality rate. Traditional drugs used in clinic are usually limited by the drug resistance and side effect and novel agents are still needed. Macrolide brefeldin A (BFA) is a well-known lead compound in cancer chemotherapy, however, with poor solubility and instability. In this study, to overcome these disadvantages, BFA was encapsulated in mixed nanomicelles based on TPGS and F127 copolymers (M-BFA). M-BFA was conferred high solubility, colloidal stability, and capability of sustained release of intact BFA. In vitro, M-BFA markedly inhibited the proliferation, induced G0/G1 phase arrest, and caspase-dependent apoptosis in human liver carcinoma HepG2 cells. Moreover, M-BFA also induced autophagic cell death via Akt/mTOR and ERK pathways. In HepG2 tumor-bearing xenograft mice, indocyanine green (ICG) as a fluorescent probe loaded in M-BFA distributed to the tumor tissue rapidly, prolonged the blood circulation, and improved the tumor accumulation capacity. More importantly, M-BFA (10 mg/kg) dramatically delayed the tumor progression and induced extensive necrosis of the tumor tissues. Taken together, the present work suggests that M-BFA has promising potential in HCC therapy.

Nucleoside transporter-guided cytarabine-conjugated liposomes for intracellular methotrexate delivery and cooperative choriocarcinoma therapy.

Gestational trophoblastic tumors seriously endanger child productive needs and the health of women in childbearing age. Nanodrug-based therapy mediated by transporters provides a novel strategy for the treatment of trophoblastic tumors. Focusing on the overexpression of human equilibrative nucleoside transporter 1 (ENT1) on the membrane of choriocarcinoma cells (JEG-3), cytarabine (Cy, a substrate of ENT1)-grafted liposomes (Cy-Lipo) were introduced for the targeted delivery of methotrexate (Cy-Lipo@MTX) for choriocarcinoma therapy in this study. ENT1 has a high affinity for Cy-Lipo and can mediate the endocytosis of the designed nanovehicles into JEG-3 cells. The ENT1 protein maintains its transportation function through circulation and regeneration during endocytosis. Therefore, Cy-Lipo-based formulations showed high tumor accumulation and retention in biodistribution studies. More importantly, the designed DSPE-PEG2k-Cy conjugation exhibited a synergistic therapeutic effect on choriocarcinoma. Finally, Cy-Lipo@MTX exerted an extremely powerful anti-choriocarcinoma effect with fewer side effects. This study suggests that the overexpressed ENT1 on choriocarcinoma cells holds great potential as a high-efficiency target for the rational design of active targeting nanotherapeutics.

Role of hormone replacement therapy in relieving oral dryness symptoms in postmenopausal women: a case control study.

BACKGROUND: To evaluate the efficacy of hormone replacement therapy in relieving oral symptoms in postmenopausal women presenting with genitourinary symptoms along with oral dryness. METHODS: A case-control study was conducted after selecting 60 postmenopausal women. Oral dryness status of all the patients was evaluated with the help of questionnaire related to oral dryness. These subjects were divided into case group and control group on the basis of response to questionnaire of oral dryness. Unstimulated saliva samples were obtained and analyzed for estimation of salivary estradiol levels by enzyme linked immune sorbent assay technique. After analyzing the result of salivary estradiol levels, case group was subjected to hormone replacement therapy (HRT). The patients were followed up for their response towards oral dryness as well as salivary estradiol levels after the therapy. RESULTS: The mean salivary estradiol level before HRT was significantly more among control group as compared to case group (p value < 0.001). Most of the patients complained of dry mouth (26 out of 30); reduced amount of saliva in the mouth (25 out of 30); dry mouth at night (28 out of 30); dry mouth during the day (25 out of 30) before HRT. These complains were significantly reduced after the therapy. The mean salivary estradiol in the case group levels increased significantly after HRT (p value < 0.001). CONCLUSION: The salivary estradiol levels were reduced in post menopausal women with the complain of xerostomia as compared to those without the complain of xerostomia. Further these levels can be recovered with the help of hormone replacement therapy.

Multifunctional Fe3O4@Polydopamine@DNA-Fueled Molecular Machine for Magnetically Targeted Intracellular Zn2+ Imaging and Fluorescence/MRI Guided Photodynamic-Photothermal Therapy.

For the precise treatment of tumors, it is necessary to develop a theranostic nanoplatform that has both diagnostic and therapeutic functions. In this article, we designed a new theranostic probe for fluorescence imaging of Zn2+ and fluorescence/MRI guided magnetically targeted photodynamic-photothermal therapy. The fluorescence imaging of Zn2+ was based on an endogenous ATP-driven DNA nanomachine that could perform repetitive stand displacement reaction. It modifies all units on a single PDA/Fe3O4 nanoparticle containing a hairpin-locked initiated strand activated by a target molecule in cells, a two-stranded fuel DNA triggered by ATP, and a two-stranded DNA track responding to an initiated strand and fuel DNA. After entering the cell, the intracellular target Zn2+ initiates the nanomachine via an autocatalytic cleavage reaction, and the machine programmatically and gradually runs on the assembled DNA track via fuel DNA driving and the intramolecular toehold-mediated stand displacement reaction. The Fe3O4 core first exhibits magnetic targeting, increasing the ability of nanoparticles to enter tumor cells at the tumor site. The Fe3O4 could also be employed as a powerful magnetic resonance imaging (MRI) contrast agent and guided therapy. Using 808 nm laser and 635 nm laser irradiation together at the tumor site, the PDA nanoshell produced an excellent photothermal effect and the TMPyP4 molecules entering the cell generated reactive oxygen species, followed by cell damage. A series of reliable experiments suggested that the Fe3O4@PDA@DNA nanoprobe showed superior fluorescence specificity, MRI, a remarkable photothermal/photodynamic therapy effect, and favorable biocompatibility. This theranostic nanoplatform offered a split-new insight into tumor fluorescence and MRI diagnosis as well as effective tumor therapy.

Polystyrene Nanoplastics-Enhanced Contaminant Transport: Role of Irreversible Adsorption in Glassy Polymeric Domain.

Nanoplastics (NPs) are becoming an emerging pollutant of global concern. A potential risk is that NPs may serve as carriers to increase the spreading of coexisting contaminants. In this study, we examined the effects of polystyrene nanoplastics (PSNPs, 100 nm), used as a model NP, on the transport of five organic contaminants of different polarity in saturated soil. The presence of low concentrations of PSNPs significantly enhanced the transport of nonpolar (pyrene) and weakly polar (2,2',4,4'-tetrabromodiphenyl ether) compounds, but had essentially no effects on the transport of three polar compounds (bisphenol A, bisphenol F, and 4-nonylphenol). The strikingly different effects of NPs on the transport of nonpolar/weakly polar versus polar contaminants could not be explained with different adsorption affinities, but was consistent with the polarity-dependent extents of desorption hysteresis. Notably, desorption hysteresis was only observed for nonpolar/weakly polar contaminants, likely because nonpolar compounds tended to adsorb in the inner matrices of glassy polymeric structure of polystyrene (resulting in physical entrapment of adsorbates), whereas polar compounds favored surface adsorption. This hypothesis was verified with supplemental adsorption and desorption experiments of pyrene and 4-nonylphenol using a dense, glassy polystyrene polymer and a flexible, rubbery polyethylene polymer. Overall, the findings of this study underscore the potentially significant environmental implication of NPs as contaminant carriers.

A ratiometric fluorometric heparin assay based on the use of CdTe and polyethyleneimine-coated carbon quantum dots.

CdTe quantum dots (QDs) were integrated with polyethyleneimine-coated carbon dots (PEI-CDs) to form a dually emitting probe for heparin. The red fluorescence of the CdTe QDs is quenched by the PEI-CDs due to electrostatic interactions. In the presence of heparin, the blue fluorescence of PEI-CDs remains unaffected, while its quenching effect on the fluorescence of CdTe QDs is strongly reduced. A ratiometric fluorometric assay was worked out. The ratio of the fluorescences at 595 and 436 nm serves as the analytical signal. Response is linear in the concentration range of 50-600 ng·mL-1 (0.1-1.2 U·mL-1) of heparin. The limit of detection is 20 ng·mL-1 (0.04 U·mL-1). This makes the method a valuable tool for heparin monitoring during postoperative and long-term care. This assay is relatively free from the interference by other analogues which commonly co-exist with heparin in samples, and it is more robust than single-wavelength based assays. Graphical abstract In the presence of heparin, the fluorescence of polyethyleneimine-coated carbon dots (PEI-CDs) at 436 nm remains unaffected, while its quenching effect on the fluorescence of CdTe at 595 nm is strongly reduced.

Electrophoretic Deposition of Gentamicin-Loaded Silk Fibroin Coatings on 3D-Printed Porous Cobalt-Chromium-Molybdenum Bone Substitutes to Prevent Orthopedic Implant Infections.

In addition to customizing shapes of metal bone substitutes for patients, the 3D printing technique can reduce the modulus of the substitutes through the design and manufacture of interconnected porous structures, achieving the modulus match between substitute and surrounding bone to improve implant longevity. However, the porous bone substitutes take more risks of postoperative infection due to its much larger surface area compared with the traditional casting solid bone substitute. Here, we prepared of gentamicin-loaded silk fibroin coatings on 3D-printed porous cobalt-chromium-molybdenum (CoCrMo) bone substitutes via electrophoretic deposition technique. Through optimization, relatively intact, continuous, homogeneous, and conformal coatings with a thickness of 2.30 ± 0.58 µm were deposited around the struts with few pore blocked. The porous metal structures exhibited no loss in mechanical properties after the anode galvanic corrosion in EPD process. The initial osteoblastic response on coatings was better than that on metal surface, including cell spreading, proliferation and cytotoxicity. Antibacterial efficacy experiments showed that the coatings had an antibacterial effect on both adherent and planktonic bacteria within 1 week. These results suggested that the beneficial properties of anode electrophoretic deposited silk fibroin coatings could be exploited to improve the biological functionality of porous structures made of medical metals.

Non-alcoholic fatty liver disease and risk of in-stent restenosis after bare metal stenting in native coronary arteries.

In-stent restenosis (ISR) remains the most common complication of percutaneous coronary intervention. Due to shared risk factors, it is postulated that non-alcoholic fatty liver disease (NAFLD) patients have an increased risk of ISR. This study aimed to determine the association between NAFLD and ISR in patients after bare metal stenting. This study included a cohort of 210 consecutive patients (150 men and 60 women) undergoing follow-up angiography. The primary end-point was angiographic ISR. Multivariate logistic regression analysis was used to identify independent risk factors for ISR. The cumulative ISR rate during follow-up was analyzed by Kaplan-Meier method. Subgroup analyses were also done for different gender. The ISR rate was 29.5%. Patients with NAFLD had a significantly higher prevalence of ISR than patients without NAFLD (43.3 vs. 16.0%, P < 0.001). In logistic regression analysis, NAFLD was associated with increased ISR, independent of low-density lipoprotein cholesterol, body mass index (adjusted odds ratio: 2.688, 95% confidence intervals: 1.285-5.537, P < 0.001). Male NAFLD patients had a higher prevalence of ISR than patients without NAFLD (48.4 vs. 15.3%, P < 0.001), while the prevalence of ISR in female patients with and without NAFLD were comparable (7.7 vs. 17.0%, P = 0.404). Kaplan-Meier analysis showed a significant association between NAFLD and ISR in all patients (log-rank P = 0.008) and in male subgroup (log-rank P = 0.033), but not in female subgroup (log-rank P = 0.313). This preliminary study suggests that NAFLD could independently associate with a high prevalence of ISR, especially in male patients.

MgO@polydopamine Nanoparticle-Loaded Photothermal Microneedle Patches Combined with Chitosan Gel Dressings for the Treatment of Infectious Wounds.

As for wound drug delivery, microneedles (MNs) have attracted wide attention. However, while effective at increasing the depth of drug delivery, traditional MNs often have limited drug loads and have difficulty penetrating scabs on wounds. Herein, we develop a drug delivery system combining MgO@polydopamine (MgO@PDA) nanoparticle-loaded photothermal MN patches and chitosan (CS) gel to inhibit the formation of scabs and deliver sufficient drugs into deep tissue. When inserted into the wound, the MN system can keep the wound bed moist and weakly acidic to inhibit the formation of scabs and accelerate wound closure. The released MgO@PDA nanoparticles from both the tips and the backing layer, which immensely increase the drug load, continuously release Mg2+ in the moist, weakly acidic wound bed, promoting tissue migration and the formation of microvessels. MgO@PDA nanoparticles show excellent antibacterial activity under near-infrared irradiation synergized with the CS gel, and the PDA coating can also overcome the adverse effects of oxidative stress. Through in vitro and in vivo experiments, the MN system showed remarkable antibacterial, antioxidant, anti-inflammatory, and pro-angiogenic effects, indicating its potential in the treatment of infectious wounds.

The Pharyngeal Packs for Dental and Otolaryngological Surgery: A Meta-Analysis of High-Quality Randomized Controlled Trials.

Background: Pharyngeal packs are employed to mitigate postoperative nausea and vomiting (PONV) and have become prevalent in dental and otolaryngological surgeries. However, their clinical efficacy continues to be a topic of debate. The objective of the present study was to conduct a quantitative assessment of the impact of pharyngeal packing in dental and otolaryngological surgeries through meta-analysis. Methods: We identified relevant randomized controlled trials (RCTs) through systematic searches of online databases, including PubMed, Embase, and Cochrane Central. Potential eligible studies were evaluated using the Jadad scoring system (range 0-5 points), with only high-quality RCTs (3 points or more) being included. The incidence of PONV, morbidity, and the level of throat pain were aggregated and estimated. Publication bias was evaluated using funnel plot symmetry and the Egger test. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was utilized to rate the evidence. Results: Ten high-quality RCTs comprising 1026 participants were ultimately included. Subsequent quantitative pooled estimation unveiled that the utilization of pharyngeal packing did not lead to a significant reduction in the incidence of nausea (P = .272), vomiting (P = .775), overall PONV (P = .118), or throat pain (P = .149). By contrast, the application of pharyngeal packs was found to significantly increase the level of throat pain (P = .003). No obvious publication bias was detected, and the majority of evidence was rated high or moderate. Conclusion: Based on the existing evidence, we conclude that pharyngeal packing lacks clinical benefit and is not advised for dental and otolaryngological surgeries.

The efficacy of gastric aspiration in reducing postoperative vomiting after oral and maxillofacial surgery: A meta-analysis.

BACKGROUND: Gastric aspiration is applied in oral and maxillofacial procedures to reduce postoperative vomiting (POV), yet its clinical benefit remains largely uncertain. Our study aimed to determine the role of gastric aspiration in the amelioration of POV by a meta-analysis. METHODS: With adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, global recognized databases, including PubMed, Embase, and Cochrane Central, were searched to obtain randomized controlled trials (RCTs) investigating the effects of gastric aspiration in oral and maxillofacial surgery. The incidence and the number of episodes of POV and the frequency of rescue antiemetic use were extracted as parametric data for pooled estimation. Funnel plots and Egger's test were utilized to assess bias. The recommendation of evidence was rated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: After detailed evaluation, 5 RCTs containing 274 participants were eventually included. The results of pooled estimation indicated that gastric aspiration could not reduce the incidence of POV (risk ratio [95% CI] = 0.94 [0.73, 1.21], P = .621), the number of episodes of POV (standard mean difference [95% CI] = -0.13 [-0.45, 0.19], P = .431) or the frequency of rescue antiemetic use (RR [95% CI] = 0.86 [0.49, 1.52], P = .609). No publication bias was detected by the funnel plot and Egger test. The overall recommendation of evidence was rated low regarding each outcome. CONCLUSION: Based on current evidence, gastric aspiration is not recommended for oral and maxillofacial surgery. Meanwhile, more large-scale high-quality RCTs are needed.

[The efficacy of iRoot BP plus in the treatment of adult carious pulp exposure and its impact on pulp blood flow].

PURPOSE: To explore the efficacy of iRoot BP plus in the treatment of adult carious pulp exposure and its impact on pulp blood flow. METHODS: A total of 126 cases of 156 permanent teeth from adult patients with carious pulp exposure who were treated from January 2020 to January 2022 were selected, the patients were divided into experimental group(63 cases with 79 permanent teeth) and control group(63 cases with 77 permanent teeth) by the envelope method. The experimental group was treated with iRoot BP plus, while the control group was treated with mineral trioxide polymer. The differences in treatment effectiveness, operation time, and tooth discoloration between the two groups were observed. Statistical analysis was performed with SPSS 22.0 software package. RESULTS: There was no significant difference in treatment success rates between the experimental group and the control group at 3, 6, and 12 months after surgery(P＞0.05). The operating time for each capsule in the experimental group was (2.53±0.41) min, which was significantly shorter than that in the control group(P＜0.05). The incidence of tooth discoloration in the experimental group at 12 months after surgery was 3.80%, which was significantly lower than that in the control group (P＜0.05). The bite force quotient and masticatory efficiency of the experimental group 12 months after operation were (16.65±1.14) Ibs and (94.45±5.65)%, which were significantly higher than those of the control group(P＜0.05). CONCLUSIONS: IRoot BP plus has good efficacy in the treatment of adult carious pulp exposure, with advantages such as convenient operation, less tooth discoloration, less inflammatory reactions and stable pulp blood flow after decline.

Fabrication of Flexible Wearable Mechanosensors Utilizing Piezoelectric Hydrogels Mechanically Enhanced by Dipole-Dipole Interactions.

Conductive hydrogels have been increasingly employed to construct wearable mechanosensors due to their excellent mechanical flexibility close to that of soft tissues. In this work, piezoelectric hydrogels are prepared through free radical copolymerization of acrylamide (AM) and acrylonitrile (AN) and further utilized in assembling flexible wearable mechanosensors. Introduction of the polyacrylonitrile (PAN) component in the copolymers endows the hydrogels with excellent piezoelectric properties. Meanwhile, significant enhancement of mechanical properties has been accessed by forming dipole-dipole interactions, which results in a tensile strength of 0.51 MPa. Flexible wearable mechanosensors are fabricated by utilizing piezoelectric hydrogels as key signal converting materials. Self-powered piezoelectric pressure sensors are assembled with a sensitivity (S) of 0.2 V kPa-1. Additionally, resistive strain sensors (gauge factor (GF): 0.84, strain range: 0-250%) and capacitive pressure sensors (S: 0.23 kPa-1, pressure range: 0-8 kPa) are fabricated by utilizing such hydrogels. These flexible wearable mechanosensors can monitor diverse body movements such as joint bending, walking, running, and stair climbing. This work is anticipated to offer promising soft materials for efficient mechanical-to-electrical signal conversion and provides new insights into the development of various wearable mechanosensors.

Placenta-anchored tadalafil liposomes rescues intrauterine growth restriction through continuous placental blood perfusion improvement.

Physiological or pathological hypoperfusion of the placenta is one of the main causes of intrauterine growth restriction (IUGR) which poses a significant risk to the health of the fetus and newborn. Tadalafil, a 5-type phosphodiesterase inhibitor, has previously been found to improve the symptoms of IUGR in various clinical studies. Unfortunately, its clinical utility is hindered by its limited water solubility, rapid metabolism, and lack of specific distribution in target tissues rendering tadalafil unable to maintain long-term placental perfusion. In this study, iRGD-modified tadalafil-loaded liposomes (iRGD-lipo@Tad) featuring a size of approximately 480 nm were designed to rectify the shortcomings of tadalafil. The prepared iRGD-lipo@Tad exhibited superior stability, sustained drug release capacity, and low cytotoxicity. The fluorescence study, tissue slice study, and drug biodistribution study together demonstrated the placenta-anchored ability of iRGD-modified liposomes. This was achieved by a dual approach consisting of the iRGD-mediated placenta-targeting effect and special particle size-mediated placenta resident effect. The pharmacokinetic study revealed a significant improvement in the in vivo process of tadalafil encapsulated by the iRGD-modified liposomes. In comparison to the tadalafil solution, the peak plasma concentration of iRGD-lipo@Tad was significantly increased, and the area under the curve was increased by about 7.88 times. In the pharmacodynamic study, iRGD-lipo@Tad achieved a continuous and efficient improvement of placental blood perfusion. This was achieved by decreasing the ratio of plasma soluble fms-like tyrosine kinase to placental growth factor and increasing the levels of cyclic guanosine monophosphate and nitric oxide. Consequently, iRGD-lipo@Tad resulted in a significant increase in embryo weight and a reduction in the miscarriage rate of N-Nitro-L-arginine methyl ester-induced IUGR pregnant mice without detectable toxicity. In summary, the nanotechnology-assisted therapy strategy presented here not only overcomes the limitations of tadalafil in the clinical treatment of IUGR but also offers new avenues to address the treatment of other placenta-originated diseases.

Chimeric nanobody-decorated liposomes by self-assembly.

Liposomes as drug vehicles have advantages, such as payload protection, tunable carrying capacity and improved biodistribution. However, due to the dysfunction of targeting moieties and payload loss during preparation, immunoliposomes have yet to be favoured in commercial manufacturing. Here we report a chemical modification-free biophysical approach for producing immunoliposomes in one step through the self-assembly of a chimeric nanobody (cNB) into liposome bilayers. cNB consists of a nanobody against human epidermal growth factor receptor 2 (HER2), a flexible peptide linker and a hydrophobic single transmembrane domain. We determined that 64% of therapeutic compounds can be encapsulated into 100-nm liposomes, and up to 2,500 cNBs can be anchored on liposomal membranes without steric hindrance under facile conditions. Subsequently, we demonstrate that drug-loaded immunoliposomes increase cytotoxicity on HER2-overexpressing cancer cell lines by 10- to 20-fold, inhibit the growth of xenograft tumours by 3.4-fold and improve survival by more than twofold.