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Pharmaceutics Jun 2024Breast cancer (BC) poses a significant threat to women's health, with triple-negative breast cancer (TNBC) representing one of the most challenging and aggressive... (Review)
Review
Breast cancer (BC) poses a significant threat to women's health, with triple-negative breast cancer (TNBC) representing one of the most challenging and aggressive subtypes due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Traditional TNBC treatments often encounter issues such as low drug efficiency, limited tumor enrichment, and substantial side effects. Therefore, it is crucial to explore novel diagnostic and treatment systems for TNBC. Multifunctional molecular probes (MMPs), which integrate target recognition as well as diagnostic and therapeutic functions, introduce advanced molecular tools for TNBC theranostics. Using an MMP system, molecular drugs can be precisely delivered to the tumor site through a targeted ligand. Real-time dynamic monitoring of drug release achieved using imaging technology allows for the evaluation of drug enrichment at the tumor site. This approach enables accurate drug release, thereby improving the therapeutic effect. Therefore, this review summarizes the recent advancements in MMPs for TNBC theranostics, encompassing the design and synthesis of MMPs as well as their applications in the field of TNBC theranostics.
PubMed: 38931924
DOI: 10.3390/pharmaceutics16060803 -
Pharmaceutics May 2024Nanoparticles conjugated with fluorescent probes have versatile applications, serving not only for targeted fluorescent imaging but also for evaluating the in vivo...
Nanoparticles conjugated with fluorescent probes have versatile applications, serving not only for targeted fluorescent imaging but also for evaluating the in vivo profiles of designed nanoparticles. However, the relationship between fluorophore density and nanoparticle behavior remains unexplored. The IR783-modified liposomes (IR783-sLip) were prepared through a modified ethanol injection and extrusion method. The cellular uptake efficiency of IR783-sLip was characterized by flow cytometry and fluorescence microscope imaging. The effects of IR783 density on liposomal in vivo behavior were investigated by pharmacokinetic studies, biodistribution studies, and in vivo imaging. The constitution of protein corona was analyzed by the Western blot assay. Dense IR783 modification improved cellular uptake of liposomes in vitro but hindered their blood retention and tumor imaging performance in vivo. We found a correlation between IR783 density and protein corona absorption, particularly IgM, which significantly impacted the liposome performance. Meanwhile, we observed that increasing IR783 density did not consistently improve the effectiveness of tumor imaging. Increasing the density of modified IR783 on liposomes is not always beneficial for tumor near-infrared (NIR) imaging yield. It is not advisable to prematurely evaluate novel nanomaterials through fluorescence dye conjugation without carefully optimizing the density of the modifications.
PubMed: 38931866
DOI: 10.3390/pharmaceutics16060744 -
Pharmaceutics May 2024We describe the current Good Manufacturing Practice (cGMP) production and subsequent characterization of eOD-GT8 60mer, a glycosylated self-assembling nanoparticle HIV-1...
We describe the current Good Manufacturing Practice (cGMP) production and subsequent characterization of eOD-GT8 60mer, a glycosylated self-assembling nanoparticle HIV-1 vaccine candidate and germline targeting priming immunogen. Production was carried out via transient expression in the human embryonic kidney 293 (HEK293) cell line followed by a combination of purification techniques. A large-scale cGMP (200 L) production run yielded 354 mg of the purified eOD-GT8 60mer drug product material, which was formulated at 1 mg/mL in 10% sucrose in phosphate-buffered saline (PBS) at pH 7.2. The clinical trial material was comprehensively characterized for purity, antigenicity, glycan composition, amino acid sequence, and aggregation and by several safety-related tests during cGMP lot release. A comparison of the purified products produced at the 1 L scale and 200 L cGMP scale demonstrated the consistency and robustness of the transient transfection upstream process and the downstream purification strategies. The cGMP clinical trial material was tested in a Phase 1 clinical trial (NCT03547245), is currently being stored at -80 °C, and is on a stability testing program as per regulatory guidelines. The methods described here illustrate the utility of transient transfection for cGMP production of complex products such as glycosylated self-assembling nanoparticles.
PubMed: 38931864
DOI: 10.3390/pharmaceutics16060742 -
Pharmaceutics May 2024Astatine-211 (At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in... (Review)
Review
Astatine-211 (At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in vivo stability of At-labeled radiopharmaceuticals remains a major challenge. This review provides a comprehensive overview of the current strategies for At radiolabeling, including nucleophilic and electrophilic substitution reactions, as well as the recent advances in the development of novel bifunctional coupling agents and labeling approaches to enhance the stability of At-labeled compounds. The preclinical and clinical applications of At-labeled radiopharmaceuticals, including small molecules, peptides, and antibodies, are also discussed. Looking forward, the identification of new molecular targets, the optimization of At production and quality control methods, and the continued evaluation of At-labeled radiopharmaceuticals in preclinical and clinical settings will be the key to realizing the full potential of At-based targeted alpha therapy. With the growing interest and investment in this field, At-labeled radiopharmaceuticals are poised to play an increasingly important role in future cancer treatment.
PubMed: 38931860
DOI: 10.3390/pharmaceutics16060738 -
Pharmaceutics May 2024The compound 6-methoxyseselin, derived from , demonstrates various therapeutic properties, including vasorelaxation, antinociceptive, anti-inflammatory, and...
The compound 6-methoxyseselin, derived from , demonstrates various therapeutic properties, including vasorelaxation, antinociceptive, anti-inflammatory, and immunomodulatory effects, along with recently discovered antiasthmatic properties. This study aimed to evaluate its preclinical pharmacokinetics and pulmonary delivery in Balb/c mice. The method involved administering the compound via inhalation and intravenous routes, followed by blood sample collection for analysis using high-performance liquid chromatography with diode array detection (HPLC-DAD). The results indicated good linearity, precision, accuracy, and stability of the compound in the biological samples. Pharmacokinetic parameters such as the rate of elimination, half-life, clearance, volume of distribution, area under the curve, and mean residence time were determined for both administration routes, showing similar profiles. The lung concentrations were notably higher than the plasma concentrations, indicating significant lung penetration. These findings suggest 6-methoxyseselin as a promising candidate for new anti-asthmatic drugs, supported by its favorable pharmacokinetic profiles and high lung penetration factors. This study represents the first exploration of the pharmacokinetics and pulmonary delivery of 6-methoxyseselin in mice, highlighting its potential for further drug development.
PubMed: 38931838
DOI: 10.3390/pharmaceutics16060714 -
Pharmaceutics May 2024Hydronephrosis resulting from unilateral ureteral obstruction (UUO) is a common cause of renal injury, often progressing to late-stage renal fibrosis or even potential...
Hydronephrosis resulting from unilateral ureteral obstruction (UUO) is a common cause of renal injury, often progressing to late-stage renal fibrosis or even potential renal failure. Renal injury and repair processes are accompanied by changes in cellular senescence phenotypes. However, the mechanism is poorly understood. The purpose of this study is to clarify the changes in senescence phenotype at different time points in renal disease caused by UUO and to further investigate whether eliminating senescent cells using the anti-senescence drug ABT263 could attenuate UUO-induced renal disease. Specifically, renal tissues were collected from established UUO rat models on days 1, 2, 7, and 14. The extent of renal tissue injury and fibrosis in rats was assessed using histological examination, serum creatinine, and blood urea nitrogen levels. The apoptotic and proliferative capacities of renal tissues and phenotypic changes in cellular senescence were evaluated. After the intervention of the anti-senescence drug ABT263, the cellular senescence as well as tissue damage changes were re-assessed. We found that before the drug intervention, the UUO rats showed significantly declined renal function, accompanied by renal tubular injury, increased inflammatory response, and oxidative stress, alongside aggravated cellular senescence. Meanwhile, after the treatment with ABT263, the rats had a significantly lower number of senescent cells, attenuated renal tubular injury and apoptosis, enhanced proliferation, reduced oxidative stress and inflammation, improved renal function, and markedly inhibited fibrosis. This suggests that the use of the anti-senescence drug ABT263 to eliminate senescent cells can effectively attenuate UUO-induced renal injury. This highlights the critical role of cellular senescence in the transformation of acute injury into chronic fibrosis.
PubMed: 38931822
DOI: 10.3390/pharmaceutics16060695 -
Sensors (Basel, Switzerland) Jun 2024The maximum detection distance is usually the primary concern of magnetic anomaly detection (MAD). Intuition tells us that larger object size, stronger magnetization and...
The maximum detection distance is usually the primary concern of magnetic anomaly detection (MAD). Intuition tells us that larger object size, stronger magnetization and finer measurement resolution guarantee a further detectable distance. However, the quantitative relationship between detection distance and the above determinants is seldom studied. In this work, unmanned aerial vehicle-based MAD field experiments are conducted on cargo vessels and NdFeB magnets as typical magnetic objects to give a set of visualized magnetic field flux density images. Isometric finite element models are established, calibrated and analyzed according to the experiment configuration. A maximum detectable distance map as a function of target size and measurement resolution is then obtained from parametric sweeping on an experimentally calibrated finite element analysis model. We find that the logarithm of detectable distance is positively proportional to the logarithm of object size while negatively proportional to the logarithm of resolution, within the ranges of 1 m~500 m and 1 pT~1 μT, respectively. A three-parameter empirical formula (namely distance-size-resolution logarithmic relationship) is firstly developed to determine the most economic sensor configuration for a given detection task, to estimate the maximum detection distance for a given magnetic sensor and object, or to evaluate minimum detectable object size at a given magnetic anomaly detection scenario.
PubMed: 38931811
DOI: 10.3390/s24124028 -
Sensors (Basel, Switzerland) Jun 2024Flexible conductive films are a key component of strain sensors, and their performance directly affects the overall quality of the sensor. However, existing flexible...
Flexible conductive films are a key component of strain sensors, and their performance directly affects the overall quality of the sensor. However, existing flexible conductive films struggle to maintain high conductivity while simultaneously ensuring excellent flexibility, hydrophobicity, and corrosion resistance, thereby limiting their use in harsh environments. In this paper, a novel method is proposed to fabricate flexible conductive films via centrifugal spinning to generate thermoplastic polyurethane (TPU) nanofiber substrates by employing carbon nanotubes (CNTs) and carbon nanofibers (CNFs) as conductive fillers. These fillers are anchored to the nanofibers through ultrasonic dispersion and impregnation techniques and subsequently modified with polydimethylsiloxane (PDMS). This study focuses on the effect of different ratios of CNTs to CNFs on the film properties. Research demonstrated that at a 1:1 ratio of CNTs to CNFs, with TPU at a 20% concentration and PDMS solution at 2 wt%, the conductive films crafted from these blended fillers exhibited outstanding performance, characterized by electrical conductivity (31.4 S/m), elongation at break (217.5%), and tensile cycling stability (800 cycles at 20% strain). Furthermore, the nanofiber-based conductive films were tested by attaching them to various human body parts. The tests demonstrated that these films effectively respond to motion changes at the wrist, elbow joints, and chest cavity, underscoring their potential as core components in strain sensors.
PubMed: 38931809
DOI: 10.3390/s24124026 -
Sensors (Basel, Switzerland) Jun 2024Digital Calibration Certificates (DCCs) are a key focus in metrology digitalization, necessitating that they satisfy the criteria for machine readability and...
Digital Calibration Certificates (DCCs) are a key focus in metrology digitalization, necessitating that they satisfy the criteria for machine readability and understandability. Current DCCs are machine-readable, but they are still missing the essential semantic information required for machine understandability. This shortfall is particularly notable in the lack of a dedicated semantic ontology for measurement terminologies. This paper proposes a domain ontology for measurement terminologies named the OMT (Ontology for Measurement Terminology), using a foundation of metrological terms from standards like the International Vocabulary of Metrology (VIM), the Guide to the Expression of Uncertainty in Measurement (GUM), and JJF1001. It also incorporates insights from models such as the SI Reference Point, the Simple Knowledge Organization System (SKOS), and the DCC Schema. The methodology was guided by Stanford's Seven-Step Method, ensuring a systematic development process tailored to the needs of metrological semantics. Through semantic expression capability verification and SPARQL query validations, the OMT has been confirmed to possess essential machine readability and understandability features. It has been successfully integrated into version 3.2.1 of DCCs across ten representative domains. This integration demonstrates an effective method for ensuring that DCCs are machine-readable and capable of interoperating within digital environments, thereby advancing the research in metrology digitization.
PubMed: 38931773
DOI: 10.3390/s24123989 -
Sensors (Basel, Switzerland) Jun 2024Electromagnetic micro mirrors are in great demand for light detection and ranging (LiDAR) applications due to their light weight and low power consumption. The driven...
Electromagnetic micro mirrors are in great demand for light detection and ranging (LiDAR) applications due to their light weight and low power consumption. The driven frequency of electromagnetic micro mirrors is very important to their performance and consumption. An electromagnetic micro mirror system is proposed in this paper. The model of the system was composed of a micro mirror, an integrated piezoresistive (PR) sensor, and a driving circuit was developed. The twisting angle of the mirror edge was monitored by an integrated PR sensor, which provides frequency feedback signals, and the PR sensor has good sensitivity and linearity in testing, with a maximum of 24.45 mV/deg. Stable sinusoidal voltage excitation and frequency tracking was realized via a phase-locked loop (PLL) in the driving circuit, with a frequency error within 10 Hz. Compared with other high-cost solutions using PLL circuits, it has greater advantages in power consumption, cost, and occupied area. The mechanical and piezoresistive properties of micro mirrors were performed in ANSYS 19.2 software. The behavior-level models of devices, circuits, and systems were validated by MATLAB R2023a Simulink, which contributes to the research on the large-angle deflection and low-power-consumption drive of the electromagnetic micro mirror. The maximum optical scan angle reached 37.6° at 4 kHz in the behavior-level model of the micro mirror.
PubMed: 38931753
DOI: 10.3390/s24123969