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1.
Nature ; 624(7992): 557-563, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37913815

ABSTRACT

Perovskite solar cells with the formula FA1-xCsxPbI3, where FA is formamidinium, provide an attractive option for integrating high efficiency, durable stability and compatibility with scaled-up fabrication. Despite the incorporation of Cs cations, which could potentially enable a perfect perovskite lattice1,2, the compositional inhomogeneity caused by A-site cation segregation is likely to be detrimental to the photovoltaic performance of the solar cells3,4. Here we visualized the out-of-plane compositional inhomogeneity along the vertical direction across perovskite films and identified the underlying reasons for the inhomogeneity and its potential impact for devices. We devised a strategy using 1-(phenylsulfonyl)pyrrole to homogenize the distribution of cation composition in perovskite films. The resultant p-i-n devices yielded a certified steady-state photon-to-electron conversion efficiency of 25.2% and durable stability.

2.
Small ; : e2402197, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682612

ABSTRACT

The conjugation of terminal ammonium salt groups with perovskite surfaces is a frequently employed technique that aims to enhance the overall performance of perovskite materials, encompassing both bulk and surface properties. Particularly, it exhibits heightened efficacy when applied to surface modification, due to its ability to mitigate defect accumulation and facilitate facile binding with the receptive sites inherent to the perovskite structure. However, the interaction of the bulk ammonium group with PbI2 has the potential to form a low-dimensional phase of perovskite, which may obstruct carrier extraction at the interface. Therefore, the surface passivators (MeO-PFACl) are designed through intramolecular potential manipulation. The combinations of the electron-donating methoxy group and π-π conjugation of the phenyl ring reduce the local potential at the reactive site of formamidinium group, making it less likely to form a low-dimension phase with perovskite. This surface passivation strategy effectively suppresses the surface nonradiative recombination and promotes the interface carrier extraction. The devices treated with MeO-PFACl have demonstrated exceptional performance, achieving a peak power conversion efficiency (PCE) of 25.88%, with an average PCE of 25.37%. These works offer a novel principle for enhancing both the efficiency and stability of PSCs using ammonium-incorporated molecules without the induction of an additional phase layer.

3.
Sensors (Basel) ; 24(7)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38610333

ABSTRACT

Geomagnetic matching navigation is extensively utilized for localization and navigation of autonomous robots and vehicles owing to its advantages such as low cost, wide-area coverage, and no cumulative errors. However, due to the influence of magnetometer measurement noise, geomagnetic localization algorithms based on single-point particle filters may encounter mismatches during continuous operation, consequently limiting their long-range localization performance. To address this issue, this paper proposes a real-time sequential particle filter-based geomagnetic localization method. Firstly, this method mitigates the impact of noise during continuous operation while ensuring real-time performance by performing real-time sequential particle filtering. Then, it enhances the long-range positioning accuracy of the method by rectifying the trajectory shape of the odometry through odometry calibration parameters. Finally, by performing secondary matching on the preliminary matching results via the MAGCOM algorithm, the positioning error of the method is further minimized. Experimental results show that the proposed method has higher positioning accuracy compared to related algorithms, resulting in reductions of over 28.58%, 37.11%, and 0.77% in RMSE, max error, and error at the end, respectively.

4.
Small ; 19(22): e2300387, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36866519

ABSTRACT

The direct electrooxidation reaction of ammonia borane (ABOR) as the anodic reaction of direct ammonia borane fuel cells (DABFCs) is greatly dependent on the properties of electrocatalysts. Both the active sites and charge/mass transfer characteristics are the key to promoting the processes of kinetics and thermodynamics, which can further improve the electrocatalytic activity. Hence, the catalyst double-heterostructured Ni2 P/Ni2 P2 O7 /Ni12 P5 (d-NPO/NP) with the optimistic redistribution of electrons and active sites is prepared for the first time. The d-NPO/NP-750 catalyst obtained after pyrolysis at 750 °C shows the outstanding electrocatalytic activity toward ABOR with an onset potential of -0.329 V vs RHE which is better than all the published catalysts. The density functional theory (DFT) computations illustrate that the Ni2 P2 O7 /Ni2 P acts as the activity enhancement heterostructure with a high d-band center (-1.60 eV) and the low activation energy barrier, while the Ni2 P2 O7 /Ni12 P5 acts as the conductivity enhancement heterostructure with the highest density of valence electrons.

5.
Sensors (Basel) ; 23(5)2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36904871

ABSTRACT

Deoxynivalenol (DON) in raw and processed grain poses significant risks to human and animal health. In this study, the feasibility of classifying DON levels in different genetic lines of barley kernels was evaluated using hyperspectral imaging (HSI) (382-1030 nm) in tandem with an optimized convolutional neural network (CNN). Machine learning methods including logistic regression, support vector machine, stochastic gradient descent, K nearest neighbors, random forest, and CNN were respectively used to develop the classification models. Spectral preprocessing methods including wavelet transform and max-min normalization helped to enhance the performance of different models. A simplified CNN model showed better performance than other machine learning models. Competitive adaptive reweighted sampling (CARS) in combination with successive projections algorithm (SPA) was applied to select the best set of characteristic wavelengths. Based on seven wavelengths selected, the optimized CARS-SPA-CNN model distinguished barley grains with low levels of DON (<5 mg/kg) from those with higher levels (5 mg/kg < DON ≤ 14 mg/kg) with an accuracy of 89.41%. The lower levels of DON class I (0.19 mg/kg ≤ DON ≤ 1.25 mg/kg) and class II (1.25 mg/kg < DON ≤ 5 mg/kg) were successfully distinguished based on the optimized CNN model, yielding a precision of 89.81%. The results suggest that HSI in tandem with CNN has great potential for discrimination of DON levels of barley kernels.


Subject(s)
Hordeum , Humans , Hyperspectral Imaging , Neural Networks, Computer , Algorithms , Support Vector Machine
6.
Gut ; 71(12): 2551-2560, 2022 12.
Article in English | MEDLINE | ID: mdl-35173040

ABSTRACT

OBJECTIVE: Patients with increased PD-L1+ host cells in tumours are more potent to benefit from antiprogrammed death-1/programmed death ligand-1 (PD-L1) treatment, but the underlying mechanism is still unclear. We aim to elucidate the nature, regulation and functional relevance of PD-L1+ host cells in hepatocellular carcinoma (HCC). DESIGN: A total of untreated 184 HCC patients was enrolled randomly. C57BL/6 mice are given injection of Hepa1-6 cells to form autologous hepatoma. ELISpot, flow cytometry and real-time PCR are applied to analyse the phenotypic characteristics of PD-L1+ cells isolated directly from HCC specimens paired with blood samples or generated from ex vivo and in vitro culture systems. Immunofluorescence and immunohistochemistry are performed to detect the presence of immune cells on paraffin-embedded and formalin-fixed samples. The underlying regulatory mechanisms of metabolic switching are assessed by both in vitro and in vivo studies. RESULTS: We demonstrate that PD-L1+ host macrophages, which constructively represent the major cellular source of PD-L1 in HCC tumours, display an HLA-DRhighCD86high glycolytic phenotype, significantly produce antitumourigenic IL-12p70 and are polarised by intrinsic glycolytic metabolism. Mechanistically, a key glycolytic enzyme PKM2 triggered by hepatoma cell derived fibronectin 1, via a HIF-1α-dependent manner, concurrently controls the antitumourigenic properties and inflammation-mediated PD-L1 expression in glycolytic macrophages. Importantly, although increased PKM2+ glycolytic macrophages predict poor prognosis of patients, blocking PD-L1 on these cells eliminates PD-L1-dominant immunosuppression and liberates intrinsic antitumourigenic properties. CONCLUSIONS: Selectively modulating the 'context' of glycolytic macrophages in HCC tumours might restore their antitumourigenic properties and provide a precise strategy for anticancer therapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Mice , Carcinoma, Hepatocellular/metabolism , B7-H1 Antigen/metabolism , Liver Neoplasms/metabolism , Mice, Inbred C57BL , Mice, Inbred Strains , Macrophages
7.
Plant Physiol ; 184(2): 607-619, 2020 10.
Article in English | MEDLINE | ID: mdl-32764132

ABSTRACT

RNA interference (RNAi) enables flexible and dynamic interrogation of entire gene families or essential genes without the need for exogenous proteins, unlike CRISPR-Cas technology. Unfortunately, isolation of plants undergoing potent gene silencing requires laborious design, visual screening, and physical separation for downstream characterization. Here, we developed an adenine phosphoribosyltransferase (APT)-based RNAi technology (APTi) in Physcomitrella patens that improves upon the multiple limitations of current RNAi techniques. APTi exploits the prosurvival output of transiently silencing APT in the presence of 2-fluoroadenine, thereby establishing survival itself as a reporter of RNAi. To maximize the silencing efficacy of gene targets, we created vectors that facilitate insertion of any gene target sequence in tandem with the APT silencing motif. We tested the efficacy of APTi with two gene families, the actin-dependent motor, myosin XI (a,b), and the putative chitin receptor Lyk5 (a,b,c). The APTi approach resulted in a homogenous population of transient P. patens mutants specific for our gene targets with zero surviving background plants within 8 d. The observed mutants directly corresponded to a maximal 93% reduction of myosin XI protein and complete loss of chitin-induced calcium spiking in the Lyk5-RNAi background. The positive selection nature of APTi represents a fundamental improvement in RNAi technology and will contribute to the growing demand for technologies amenable to high-throughput phenotyping.


Subject(s)
Genetic Techniques , Multigene Family , RNA Interference , Adenine Phosphoribosyltransferase , Bryopsida , Genes, Plant
8.
Opt Lett ; 46(10): 2252-2255, 2021 May 15.
Article in English | MEDLINE | ID: mdl-33988557

ABSTRACT

Metasurfaces consisting of different shapes of resonant units are used to manipulate light beams at subwavelength scales. In many cases, interactions among the resonant units are suppressed or avoided because of mode splitting in metasurfaces. Here we theoretically and numerically investigate metasurfaces composed of multiple antennas with anti-Hermitian coupling in a single layer. By utilizing the anti-Hermitian coupling, the results show that antennas with similar resonance frequencies at a subwavelength distance can individually absorb their corresponding frequency photons. The antennas whose reflection phase can be tailored by changing the number of antennas have the same resonance frequencies. This Letter paves the way for various potential applications in broadband absorption, photon sorting, image sensors, and phase modulation.

9.
Biotechnol Bioeng ; 118(5): 1779-1792, 2021 05.
Article in English | MEDLINE | ID: mdl-33491767

ABSTRACT

Incurable breast cancer bone metastasis causes widespread bone loss, resulting in fragility, pain, increased fracture risk, and ultimately increased patient mortality. Increased mechanical signals in the skeleton are anabolic and protect against bone loss, and they may also do so during osteolytic bone metastasis. Skeletal mechanical signals include interdependent tissue deformations and interstitial fluid flow, but how metastatic tumor cells respond to each of these individual signals remains underinvestigated, a barrier to translation to the clinic. To delineate their respective roles, we report computed estimates of the internal mechanical field of a bone mimetic scaffold undergoing combinations of high and low compression and perfusion using multiphysics simulations. Simulations were conducted in advance of multimodal loading bioreactor experiments with bone metastatic breast cancer cells to ensure that mechanical stimuli occurring internally were physiological and anabolic. Our results show that mechanical stimuli throughout the scaffold were within the anabolic range of bone cells in all loading configurations, were homogenously distributed throughout, and that combined high magnitude compression and perfusion synergized to produce the largest wall shear stresses within the scaffold. These simulations, when combined with experiments, will shed light on how increased mechanical loading in the skeleton may confer anti-tumorigenic effects during metastasis.


Subject(s)
Biomechanical Phenomena/physiology , Bioreactors , Bone Neoplasms , Breast Neoplasms , Tissue Engineering/methods , Tumor Microenvironment/physiology , Bone Neoplasms/physiopathology , Bone Neoplasms/secondary , Breast Neoplasms/pathology , Breast Neoplasms/physiopathology , Female , Humans , Stress, Mechanical
10.
Pharmacol Res ; 174: 105966, 2021 12.
Article in English | MEDLINE | ID: mdl-34728366

ABSTRACT

Microbiota has been implicated in the regulation of tumor progression and therapeutic efficacy. However, the effect of microbiota on disease progression is context dependent, differing according to tumor types, therapeutic regimens, and composition of the microbiota, calling for a deeper understanding of host-microbiome interactions. Previous studies have demonstrated that gut microbiota influences disease progression by regulating local and systemic immunity. Notably, with the advent of next-generation sequencing technology, intratumoral microbiota has also been found and constitutes an important component of the tumor microenvironment. In this review, we summarize recent knowledge about the identification of intra-tumor microbiota and discuss the role of gut and intratumoral microbiota in solid tumors in the angle of immune microenvironment interaction. Furthermore, we discuss how these findings may benefit current anti-cancer approaches. Key problems to be solved in ongoing and future research are highlighted.


Subject(s)
Gastrointestinal Microbiome , Neoplasms/microbiology , Neoplasms/therapy , Animals , Humans , Neoplasms/immunology , Tumor Microenvironment/immunology
11.
Mol Plant Microbe Interact ; 33(7): 911-920, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32240064

ABSTRACT

A characteristic feature of a plant immune response is the increase of the cytosolic calcium (Ca2+) concentration following infection, which results in the downstream activation of immune response regulators. The bryophyte Physcomitrella patens has been shown to mount an immune response when exposed to bacteria, fungi, or chitin elicitation, in a manner similar to the one observed in Arabidopsis thaliana. Nevertheless, whether the response of P. patens to microorganism exposure is Ca2+ mediated is currently unknown. Here, we show that P. patens plants treated with chitin oligosaccharides exhibit Ca2+ oscillations, and that a calcium ionophore can stimulate the expression of defense-related genes. Treatment with chitin oligosaccharides also results in an inhibition of growth, which can be explained by the depolymerization of the apical actin cytoskeleton of tip growing cells. These results suggest that chitin-triggered calcium oscillations are conserved and were likely present in the common ancestor of bryophytes and vascular plants.


Subject(s)
Bryopsida/immunology , Calcium/pharmacology , Chitin/pharmacology , Bryopsida/genetics , Gene Expression Regulation, Plant , Plant Immunity , Plant Proteins/genetics , Plant Proteins/immunology
12.
Phys Rev Lett ; 123(17): 173901, 2019 Oct 25.
Article in English | MEDLINE | ID: mdl-31702244

ABSTRACT

The interaction between quantum two-level systems is typically short range in free space and in most photonic environments. We show that diminishing momentum isosurfaces with equal frequencies can create a significantly extended range of interaction between distant quantum systems. The extended range is robust and does not rely on a specific location or orientation of the transition dipoles. A general relation between the interaction range and properties of the isosurface is described for structured photonic media. It provides a new way to mediate long-range quantum behavior.

13.
Biotechnol Bioeng ; 115(4): 1076-1085, 2018 04.
Article in English | MEDLINE | ID: mdl-29278411

ABSTRACT

Breast cancer most frequently metastasizes to the skeleton. Bone metastatic cancer is incurable and induces wide-spread bone osteolysis, resulting in significant patient morbidity and mortality. Mechanical cues in the skeleton are an important microenvironmental parameter that modulate tumor formation, osteolysis, and tumor cell-bone cell signaling, but which mechanical signals are the most beneficial and the corresponding molecular mechanisms are unknown. We focused on interstitial fluid flow based on its well-known role in bone remodeling and in primary breast cancer. We created a full-scale, microCT-based computational model of a 3D model of bone metastasis undergoing applied perfusion to predict the internal mechanical environment during in vitro experimentation. Applied perfusion resulted in uniformly dispersed, heterogeneous fluid velocities, and wall shear stresses throughout the scaffold's interior. The distributions of fluid velocity and wall shear stress did not change within model sub-domains of varying diameter and location. Additionally, the magnitude of these stimuli is within the range of anabolic mechanical signals in the skeleton, verifying that our 3D model reflects previous in vivo studies using anabolic mechanical loading in the context of bone metastasis. Our results indicate that local populations of cells throughout the scaffold would experience similar mechanical microenvironments.


Subject(s)
Biomimetic Materials/chemistry , Computer Simulation , Perfusion , Stress, Mechanical , Tissue Engineering/methods , Bioreactors , Durapatite/chemistry , Humans , Hydrodynamics , Polyglactin 910/chemistry , Porosity , Sodium Chloride/chemistry , Tissue Scaffolds/chemistry
14.
Front Immunol ; 15: 1273358, 2024.
Article in English | MEDLINE | ID: mdl-38352885

ABSTRACT

Introduction: Previous observational studies have established a correlation between Graves' disease(GD) and systemic lupus erythematosus(SLE). However, whether a causal relationship exists between these two diseases remains unknown.We utilized Mendelian randomization to infer the causal association between GD and SLE. Methods: This study employed GWAS summary statistics of GD and SLE in individuals of Asian descent. The random effect inverse variance weighted (IVW) method was utilized to aggregate the causal effect estimates of all SNPs. Cochran's Q values were computed to evaluate the heterogeneity among instrumental variables. Sensitivity analyses such as MR-Egger method, median weighting method, leave-one-out method, and MR-PRESSO method were used to test whether there was horizontal pleiotropy of instrumental variables. Results: Our study found genetically predicted GD may increase risk of SLE (OR=1.17, 95% CI 0.99-1.40, p=0.069). Additionally, genetically predicted SLE elevated the risk of developing GD by 15% (OR=1.15, 95% CI 1.05-1.27, p= 0.004). After correcting for possible horizontal pleiotropy by excluding outlier SNPs, the results suggested that GD increased the risk of SLE (OR=1.27, 95% CI 1.09-1.48, p =0.018), while SLE also increased the risk of developing GD (OR=1.13, 95% CI 1.05-1.22, p =0.003). Conclusion: The findings of the study indicate that there may be a correlation between GD and SLE, with each potentially increasing the risk of the other. These results have important implications for the screening and treatment of patients with co-morbidities in clinical settings, as well as for further research into the molecular mechanisms underlying the relationship between GD and SLE.


Subject(s)
Graves Disease , Lupus Erythematosus, Systemic , Humans , Mendelian Randomization Analysis , Graves Disease/genetics , Lupus Erythematosus, Systemic/genetics , Polymorphism, Single Nucleotide
15.
J Colloid Interface Sci ; 662: 719-726, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38368829

ABSTRACT

The utilization of carbon quantum dots (CQDs) for photothermal therapy has emerged as a hot research topic. However, there has been limited research on killing one single cancer cell which is critical in reducing unnecessary damage to the surrounding healthy tissues. In this work, we developed a two-photon fluorescence-guided precise photothermal therapy in a single human malignant melanoma (A375) cancer cell utilizing bifunctional N-doped CQDs. Resulting from the two-photon fluorescence of the CQDs, one single cancer cell can be located and simultaneously destroyed by the photothermal effect of the same CQDs. Specifically, the balanced two-photon absorption cross-section (7000 GM) and photoluminescence quantum yield (8.4%) of the CQDs enable the fluorescence-guided photothermal treatment to be achieved in only 5 s under the irradiation of 800 nm laser of 27.5 mW, much faster than the control experiment without the guidance of fluorescence. The heat generated by the aggregated CQDs is in sufficient amounts while being confined in a small area, as evidenced by the numerical simulations and photothermal experiments, to limit the range of thermal treatment in the cells. This work provides a new approach for realizing photothermal therapy with minimal damage and establishes a new application scenario of CQDs for precise tumor ablation.


Subject(s)
Neoplasms , Quantum Dots , Humans , Photothermal Therapy , Carbon , Neoplasms/therapy , Spectrometry, Fluorescence
16.
J Colloid Interface Sci ; 661: 709-719, 2024 May.
Article in English | MEDLINE | ID: mdl-38320407

ABSTRACT

The exploration of bifunctional catalyst with economic, durable, and efficient performance plays a crucial role to boost both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in overall water splitting. Herein, we report a feasible strategy to design effective heterostructure between CoP and Ti3C2Tx MXene (denoted as CoP/Ti3C2Tx). This approach allows for the growth of CoP nanoparticles with uniform size of 5 nm on the Ti3C2Tx MXene, further enhancing the water electrolysis efficiency. The CoP/Ti3C2Tx bifunctional catalyst demonstrates an exceptional HER activity with a satisfactory overpotential of 103 mV at 10 mA cm-2, and also can drive 10 mA cm-2 for OER with the overpotential of 312 mV in 1.0 M KOH. Moreover, the CoP/Ti3C2Tx-based electrolyzer exhibits high electrochemical stability for 24 h with a low required voltage of 1.66 V at 10 mA cm-2. The density functional theory (DFT) calculations reveal that the introduction of Ti3C2Tx MXene significantly adjusts d-band center towards Fermi level and expand total density of states, resulting in great electrical conductivity, enhanced water adsorption, and activation. This study provides an available mode for effective design and construction of non-noble-metal-based dual-functional catalyst toward practical energy conversion.

17.
Int J Pharm ; 658: 124213, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38729382

ABSTRACT

Safe and effective Cu2+ supplementation in local lesion is crucial for minimizing toxicity of DSF-based chemotherapy. Targeted delivery of Cu2+ appears more promising. Intraperitoneal chemotherapy for peritoneal carcinoma (PC) establishes "face-to-face" contact between targeted nanocarriers and tumor tissue. Herein, this study developed a biodegradable, injectable thermosensitive hydrogel that coencapsulating DSF submicroemulsion (DSF-SE) and folate-modified liposome loading glycyrrhizic acid-Cu (FCDL). FCDL acted as 'beneficial horse' to target the tumor-localized folate receptor, thus liberating Cu2+ in tumor nidus. The prepared FCDL and DSF-SE were found with uniform sizes (160.2 nm, 175.4 nm), low surface charge (-25.77 mV, -16.40 mV) and high encapsulation efficiency (97.93 %, 90.08 %). In vitro drug release profile of FCDL, DSF-SE and FCDL&DSF-SE@G followed a sustained release pattern. And the release behavior of Cu2+ from FCDL was pH-related, i.e., Cu2+ was released faster under acidic condition. When FCDL and DSF-SE were loaded into an PLGA-PEG-PLGA-based hydrogel system, FCDL&DSF-SE@G was formed to ensure separated delivery of Cu2+ and DSF in space but synchronized release over time. The rheology experiment showed a satisfactory gelling temperature of 32.7 °C. In vitro cytotoxicity study demonstrated that FCDL&DSF-SE@G significantly lowered the IC50 of free Cu2+/DSF, Cu2+/DSF hydrogel and non-targeted analogue by almost 70 %, 65 % and 32 %, respectively. Accordingly, in tumor-bearing mice, FCDL&DSF-SE@G augmented the tumor inhibition rates for the same formulations by 352 %, 145 % and 44 %, respectively. The main mechanism was attributed to higher uptake of FCDL and DSF-SE, resulting in increased Cu(DDTC)2 formation, ROS production and cell apoptosis. In conclusion, this targeted nanotherapy approach with dual-nanocarriers loaded hydrogel system, with its focus on face-to-face contact between nanocarriers and tumor tissues in the peritoneal cavity, holds significant promise for intraperitoneal chemotherapy in PC.


Subject(s)
Copper , Delayed-Action Preparations , Drug Liberation , Folic Acid , Liposomes , Folic Acid/chemistry , Folic Acid/administration & dosage , Animals , Copper/chemistry , Copper/administration & dosage , Cell Line, Tumor , Humans , Glycyrrhizic Acid/chemistry , Glycyrrhizic Acid/administration & dosage , Hydrogels/chemistry , Nanoparticles/chemistry , Mice, Inbred BALB C , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Mice , Temperature , Cell Survival/drug effects , Female , Mice, Nude , Drug Carriers/chemistry , Polyethylene Glycols/chemistry
18.
ACS Nano ; 18(24): 15557-15575, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38837909

ABSTRACT

Tumor vaccines have demonstrated a modest response rate, primarily attributed to their inefficient delivery to dendritic cells (DCs), low cross-presentation, DC-intrinsic immunosuppressive signals, and an immunosuppressive tumor microenvironment (TME). Here, draining lymph node (DLN)-targeted and tumor-targeted nanovaccines were proposed to address these limitations, and heterocyclic lipidoid (A18) and polyester (BR647) were synthesized to achieve dual-targeted cancer immunotherapy. Meanwhile, oligo hyaluronic acid (HA) and DMG-PEG2000-Mannose were incorporated to prepare dual-targeted nanovaccines encapsulated with STAT3 siRNA and model antigens. The nanovaccines were designed to target the DLN and the tumor, facilitating the delivery of cargo into the cytoplasm. These dual-targeted nanovaccines improved antigen presentation and DC maturation, activated the stimulator of interferon genes (STING) pathway, enhanced the pro-apoptotic effect, and stimulated antitumor immune responses. Additionally, these dual-targeted nanovaccines overcame immunosuppressive TME, reduced immunosuppressive cells, and promoted the polarization of tumor-associated neutrophils from N2 to N1. Among the four dual-targeted nanovaccines that induced robust antitumor responses, the heterocyclic lipidoid@polyester hybrid nanovaccines (MALO@HBNS) demonstrated the most promising results. Furthermore, a combination strategy involving MALO@HBNS and an anti-PD-L1 antibody exhibited an immensely powerful anticancer role. This work introduced a dual-targeted nanovaccine platform for antitumor treatment, suggesting its potential combination with an immune checkpoint blockade as a comprehensive anticancer strategy.


Subject(s)
Cancer Vaccines , Immunotherapy , Nanoparticles , Polyesters , Cancer Vaccines/immunology , Cancer Vaccines/chemistry , Animals , Mice , Polyesters/chemistry , Nanoparticles/chemistry , Mice, Inbred C57BL , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Dendritic Cells/immunology , Female , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/chemistry , Lipids/chemistry , Humans , Neoplasms/therapy , Neoplasms/immunology , Cell Line, Tumor , RNA, Small Interfering/chemistry , Hyaluronic Acid/chemistry , Nanovaccines
19.
Int J Pharm X ; 7: 100258, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38912324

ABSTRACT

Vincristine (VCR), as a cytotoxic drug, is used clinically to treat acute lymphatic leukemia and breast cancer, and commonly used clinically as vincristine sulfate (VCRS). However, its clinical use is limited by unpredictable pharmacologic characteristics, a narrow therapeutic index, and neurotoxicity. The pH gradient method was used for active drug loading of VCRS, and the process route mainly includes the preparation of blank liposomes and drug-loaded liposomes. VCRS liposomes had suitable particle size, high encapsulation efficiency and good stability. The loading and release kinetics of VCRS liposomes were explored. By calculating the changes of encapsulation efficiency with time at different temperatures, it was confirmed that the drug-loading process of liposomes exhibited a first-order kinetic feature, and the activation energy required for the reaction was determined as 20.6 kcal/mol. The release behavior at different pH was also investigated, and it was demonstrated that the release behavior conformed to the first-order model, suggesting that the release mechanism of VCRS was simple transmembrane diffusion. VCRS liposomes also enhanced in vitro and in vivo antitumor activity. Thus, VCRS liposomes showed great potential for VCRS delivery, and the loading and release kinetics were well researched to provide a reference for investigating active drug loading liposomes.

20.
Micromachines (Basel) ; 14(7)2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37512638

ABSTRACT

Thermogalvanic hydrogel, an environmentally friendly power source, enable the conversion of low-grade thermal energy to electrical energy and powers microelectronic devices in a variety of scenarios without the need for additional batteries. Its toxicity, mechanical fragility and low output performance are a hindrance to its wide application. Here, we demonstrate thermoelectric gels with safe non-toxic, recyclable, highly transparent and flexible stretchable properties by introducing gelatin as a polymer network and SO3/42- as a redox electric pair. When the temperature difference is 10 K, the gel-based thermogalvanic cell achieves an open-circuit voltage of about 16.2 mV with a maximum short-circuit current of 39 µA. Furthermore, we extended the application of the Gel-SO3/42- gel to monitor the temperature of hot or cold food, enabling self-powered sensing for food temperature detection. This research provides a novel concept for harvesting low-grade thermal energy and achieving safe and harmless self-driven temperature monitoring.

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