Specific Release Research Articles

TMIC-85. THE MECHANISM OF COMBINED HYDROGEN-CHEMICAL THERAPY BASED ON ACTIVE MAGNESIUM MICROMOTORS FOR INHIBITING GLIOBLASTOMA RECURRENCE BY MODULATING TUMOR MICROENVIRONMENT

Abstract OBJECTIVE This study aims to develop an innovative therapeutic strategy to prevent postoperative recurrence of Glioblastoma (GBM), a condition with poor prognosis and high recurrence rates. The focus is on exploring the efficacy of synergistic hydrogen-chemical therapy in inhibiting GBM recurrence, especially by reducing surgery-induced inflammation and enhancing the sensitivity of GBM cells to chemotherapy. METHODS The study employed the fabrication of Mg-Motor-DOX using a biodegradable polylactic acid-glycolic acid copolymer (PLGA) and gelatin containing Doxorubicin (DOX). The reaction of Mg with water produces hydrogen (H2), which aids in scavenging reactive oxygen species (ROS) and inflammation, alongside the specific release of chemotherapy drugs at the tumor site. A thermosensitive hydrogel was developed for in situ delivery of Mg-Motor-DOX to the tumor residual cavity. Additionally, RNA sequencing was used to study the transcriptional changes in the GBM tumor microenvironment (TME) induced by this therapy. RESULTS The study presents initial evidence of the in vivo efficacy of synergistic hydrogen-chemical therapy against GBM. The Mg-Motor-DOX mediated therapy not only scavenged ROS and reduced inflammation but also specifically released chemotherapy drugs at the tumor site, enhancing their effectiveness. RNA-Seq technology elucidated the molecular mechanisms underlying the therapy’s efficacy, revealing significant transcriptional changes in the GBM TME. CONCLUSION Synergistic hydrogen-chemical therapy, facilitated by Mg-Motor-DOX, shows promising potential in preventing the postoperative recurrence of GBM. This innovative approach effectively combines anti-inflammatory benefits and enhanced chemosensitivity, offering new strategies for GBM treatment. The molecular insights provided by RNA-Seq technology contribute to a deeper understanding of tumor treatment mechanisms, paving the way for future clinical applications.

TMIC-21. PYK2/MAPK/ERK SIGNALING PATHWAY REGULATES EXTRACELLULAR VESICLE RELEASE IN GLIOBLASTOMA

Abstract Glioblastoma (GBM), the deadliest brain cancer, typically proves fatal within a year despite treatment. Tumor-associated myeloid cells (TAMs) support GBM growth, treatment resistance, and immune surveillance. Extracellular vesicles (EVs) facilitate communication between tumor and TAMs, exchanging proteins, lipids, RNA, and genetic material. As EVs can travel through the bloodstream to distant tissues, they trigger signaling pathways and metabolic changes in remote organs while also recruiting bone marrow-derived cells and modulating immune responses. Therefore, EVs serve as a crucial mechanism for the distant regulation of the tumor’s immune microenvironment. We hypothesize that Pyk2/MAPK/Erk signaling regulates EV release by modulating the actin cytoskeleton, impacting TAM infiltration and activation in tumors. This study aims to investigate the role of Pyk2/MAPK/Erk in specific EV release in GBM cells, potentially offering insights into therapeutic targets. Using confocal imaging and flow cytometric analysis of EVs, purified from medium conditioned from human primary GBM cell lines with and without Pyk2 CRISPR/Cas9 knock-out (Pyk2KO), the study identified that Pyk2KO cells do not release the population of EVs with diameter bigger then 600nm and up-regulate release of smaller EVs. Additionally, flow cytometric analysis of EVs, released from cells, fluorescently labeled with membrane dye carboxyfluorescein diacetate succinimidyl ester (CFDA-SE), detected 14% of CFSE+ events in EV’s population, purified from Pyk2WT, vs. to 2.5% from Pyk2KO cells. Membrane labeling of cells enables the tracking of microvesicles (MV) shedding and was used to differentiate between MV and ES based on the process of their biogenesis. Considering that larger size and the transition of fluorescence from the plasma membrane are indicative of MVs, our data indicate that Pyk2 is involved in the regulation of MV release. FUNDING: PRSTRT2022 and NIH Grant 1R15CA287203

Systematic review of the economic impact of novel Mycobacterium tuberculosis specific antigen-based skin tests for detection of TB infection compared with tuberculin skin test and interferon-gamma release assays.

The Purified Protein Derivative tuberculin skin tests (TST) and blood-based Mycobacterium tuberculosis (M.tb) specific interferon-gamma release assays (IGRA) are the currently used tests for identifying individuals with TB infection for preventive treatment. However, challenges around access and implementation have limited their use. Novel M.tb specific skin tests (TBST) such as Diaskintest, ESAT6-CFP10 (C-TST), C-Tb (also known as Cy-Tb), and DPPD may provide accurate and scalable options but evidence synthesis on their economic impact is lacking. We conducted two separate systematic reviews to compare the costs and cost-effectiveness of (1) the novel skin tests TBST (primary), and (2) TST and IGRA tests (secondary), to support WHO guideline development. We searched for articles presenting economic evaluations of the diagnostic tests using a health provider perspective and related to TB infection in humans. We considered papers written in English, Chinese or Russian. In the primary review, eight studies for novel TBST were found. One study in Brazil assessed cost-effectiveness of C-TST and Diaskintest and seven in Russia assessed the Diaskintest, while none evaluated C-Tb or DPPD. The review showed on average, Diaskintest kit costs (in 2021 USD) $1.60 (1.50 - 1.70), while full unit costs were estimated at $5.07. C-TST unit cost was $9.96. The second review found 32 articles on IGRA and/or the TST. These presented an average TST full unit cost of $37.88, and $87.81 for IGRA. Studies' quality for TBST was limited while high-quality studies were found for TST and IGRA tests. In conclusion, there is limited evidence regarding the costs and cost-effectiveness of novel TBST. Conversely, there is substantial evidence for TST and IGRA tests, but most studies were performed in high-income and low-TB burden settings and their cost-effectiveness varied between and within risk groups without clear economic consensus.

Preparation of Disulfide/Trisulfide Core-Cross-Linked Polycarbonate Nanocarriers for Intracellular Reduction-Triggered Drug Release.

Polymeric nanocarriers have attracted significant attention in the field of anticancer drug delivery due to their unique advantages. However, designing nanocarriers that can maintain stability in the bloodstream while achieving specific drug release within tumor cells remains a major challenge. To address this issue, constructing reversible cross-linked polymeric nanocarriers that are sensitive to the intracellular reducible glutathione (GSH) characteristic of the tumor microenvironment is a promising strategy. Based on this, we designed and synthesized two novel six-membered bicyclic carbonate monomers containing disulfide (DSBC) and trisulfide (TSBC) bonds. Through a one-step ring-opening polymerization, a series of reduction-sensitive polycarbonate copolymers (i.e., PEG-PDSBC and PEG-PTSBC) were prepared, and doxorubicin (DOX)-loaded nanoparticles were fabricated using a nanoprecipitation method. The in vitro drug release behaviors of these nanoparticles were systematically investigated. The results showed that these polymers, due to the cross-linked structure formed by the ring-opening polymerization of their bicyclic monomers, could self-assemble into stable nanoparticles. Under different concentrations of glutathione, DOX-loaded PEG-PTSBC nanoparticles demonstrated faster drug release, indicating more optimized intracellular drug release properties. Further cytotoxicity experiments revealed that both types of blank nanoparticles exhibited good biocompatibility with the 4T1 and NIH-3T3 cells. Fluorescence microscopy and flow cytometry results further indicated that DOX-loaded PEG-PTSBC nanoparticles released more drugs in 4T1 cells, significantly inhibiting tumor cell growth compared with DOX-loaded PEG-PDSBC nanoparticles, with no noticeable difference in NIH-3T3 normal cells. In conclusion, this study suggests that trisulfide cross-linked polycarbonate-based nanocarriers hold promise as an anticancer drug delivery system that combines stability in the bloodstream with specific intracellular drug release, offering new insights for the development of novel, efficient, and safe anticancer nanomedicines.

Dynamic Chemistry of DNA-Based Nanoassemblies in Living Cells.

ConspectusIn recent years, the controlled assembly/disassembly of exogenous chemical components inside cells has become an emerging approach to regulating cell functions. However, the construction of dynamic material chemistry systems in living cells always remains highly challenging due to the complicated intracellular microenvironment. Nucleic acid is a category of biological components that can achieve efficient molecular assembly via specific base-pairing and perform biological functions in the intracellular microenvironment. Deoxyribonucleic acid (DNA) molecules exhibit the superior performance of intracellular assembly, including sequence programmability, molecule recognition ability, and nanostructure predictability, as well as the unique biological functions that traditional synthetic polymers do not carry, showing great superiority in the construction of dynamic material chemistry systems. Moreover, the technologies of DNA synthesis are relatively mature, and the conjugation of DNA with functional small molecules can be achieved through established chemical synthesis methods, facilitating the construction of DNA-based dynamic materials with more functions. In addition, a few specific DNA molecules have been proven to show responsiveness toward different stimuli, functioning as dynamic modules.In this Account, we summarize our recent work in dynamic chemistry of DNA-based nanoassemblies in living cells from the perspective of stimulus types including enzyme, H+, glutathione (GSH), adenosine triphosphate (ATP), and light. Upon the specific stimuli, DNA-based nanoassemblies undergo precise assembly in living cells, executing disassembly or aggregation, which consequently affects the functions and behaviors of living cells. In the first part, we describe the interactions between DNA-based nanoassemblies and intracellular enzymes, namely the enzymatic cleavage of intracellular enzymes on the DNA or RNA sequences. In the second part, we summarize the effects of H+ in lysosomes on DNA-based nanoassemblies, including the formation of a tetraplex i-motif structure and the decomposition of acid-degradable polymeric coating. In the third part, we discuss the mechanism of GSH responsiveness of DNA-based nanoassemblies, including the breaking of disulfide bonds and reduction-responsive nanoparticles. In the fourth part, we describe the ATP-mediated conformational transition for the specific release of functional RNA sequences. In the fifth part, we demonstrate the light-mediated spatiotemporally dynamic chemistry of DNA-based nanoassemblies. In summary, based on the achievements of our group in the study of dynamic chemistry of DNA-based nanoassemblies, the assembly, disassembly, and reassembly in living cells are well-controlled, the regulation of cellular functions are explored, and the new strategies for cancer therapeutics are demonstrated. We envision that our work on the dynamic chemistry of DNA-based nanoassembly is a new paradigm for constructing dynamic material chemistry systems inside living cells, and will facilitate the development of precision medicine.

ATP-activated Fe(Ⅲ)/carbon dots assemblies for in situ generating nanozyme and simultaneously monitoring tumor cell ferroptosis

The integration of nanomedicine and nanocatalysis has currently resulted in the emergence of synthesized nanozymes with disruptive potential in alternative cancer therapy. However, the in situ synthesis of nanozymes using an intracellular components remains a formidable challenge. In this study, the inactivated Fe(Ⅲ)/carbon dots nanoassemblies (Fe/CDs-A) were prepared through Fe3+-induced assembly of red emissive CDs. In tumor cells overexpressing adenosine triphosphate (ATP), Fe/CDs-A can be activated and disassembled, causing the specific release of CDs and simultaneous formation of Fe3+-ATP nanocomplexes in situ due to the enhanced coordination between intracellular ATP and Fe3+. Intriguingly, Fe3+-ATP nanocomplexes were found to possess peroxidase (POD)-like activity, efficiently generating highly toxic •OH in the presence of acidic H2O2 in tumor cells, thereby inducing tumor cells ferroptosis. Simultaneously, the released CDs initially penetrate the lysosomes of tumor cells and ultimately accumulate in the nuclei of dead/dying cells, achieving real-time monitoring cell death process through their recovered red emission. Overall, for the first time, the well-designed Fe/CDs-A demonstrates its capability as ATP-triggered inducers for in situ generation of nanozymes and specific release of CDs. This study offers a novel pathway for in situ generation of nanozymes for precise cancer therapy.

Deployment of tethered gene drive for confined suppression in continuous space requires avoiding drive wave interference.

Gene drives have great potential for suppression of pest populations and removal of exotic invasive species. CRISPR homing suppression drive is a powerful but unconfined drive, posing risks of uncontrolled spread. Thus, developing methods for confining a gene drive is of great significance. Tethered drive combines a confined system such as Toxin-Antidote Recessive Embryo drive with a strong drive such as a homing suppression drive. It can prevent the homing drive from spreading beyond the confined drive and can be constructed readily, giving it good prospects for future development. However, we have found that care must be taken when deploying tethered drive systems in some scenarios. Simulations of tethered drive in a panmictic population model reveal that successful deployment requires a proper release ratio between the two components, tailored to prevent the suppression drive from eliminating the confined system before it has the chance to spread. Spatial models where the population moves over a one-dimensional landscape display a more serious phenomenon of drive wave interference between the two tethered drive components. If the faster suppression drive wave catches up to the confined drive wave, success is still possible, but it is dependent on drive performance and ecological parameters. Two-dimensional simulations further restrict the parameter range for drive success. Thus, careful consideration must be given to drive performance and ecological conditions, as well as specific release proposals for potential application of tethered drive systems.

Preparation of high-labeled graphene oxide by tritium thermal activation method for application in the betavoltaic cell of a nuclear battery

Possibility of tritium introduction into graphene oxide (GO) by tritium thermal activation method was demonstrated. It has been established that, in order to obtain the highest possible specific radioactivity, thin films of GO with a thickness of 5.6 mg/m2 must be treated with tritium atoms. The experiment provided at 77 K showed a number of advantages. Under these conditions, the specific activity of [3H]GO of 2.6 Ci/mg was reached when calculated by the mass of the initial GO (0.7 Ci/mg if purified to remove the labile tritium). Specific energy release in [3H]GO with such specific activity is 22.3 W/kg, which is enough for its application as a component of an atomic battery.

Combustion synthesis of the (Ti,Zr)B2-(Zr,Ti)C eutectic composites: Structure formation and properties

The macrokinetic characteristics of combustion of the quaternary Ti-Zr-B-C mixture as well as the mechanism and stages of phase formation for the synthesis products were investigated. The mechanical and thermophysical properties of the hot-pressed boride/carbide ceramics with eutectic composition (Ti,Zr)B2-43%at.(Zr,Ti)C were measured. Preliminary mechanical alloying (MA) of the (Zr + Ti) mixture was shown to yield Ti/Zr granules having a laminar structure and consisting of alternating layers of titanium, zirconium, and (Zr,Ti)ss solid solution. The method used to prepare reaction mixtures and the initial temperature T0 increased within the range of 20–370 °C have virtually no effect on combustion temperature, which is 2260–2400 °C, while higher T0 increases the combustion rate by a factor of 1.5–2. The use of MA Ti/Zr granules reduces the combustion rate as well as the specific heat release amount and the heat release rate. Time-resolved X-ray diffraction data showed that binary carbides (Zr1-xTix)C and diborides (Ti1-yZry)B2 of variable stoichiometry are formed in the combustion wave of the Ti-Zr-B-C reaction mixtures within less than 0.25 s. The carbide and diboride phases are formed simultaneously; the use of MA Ti/Zr granules in the reaction mixtures reduces the content of solid solutions of variable stoichiometry among the reaction products. The ceramics fabricated using a combination of combustion synthesis and hot pressing have a dense and homogeneous structure that consist of bonded grains of the diboride (Ti0.80Zr0.20)B2 and carbide (Zr0.83Ti0.17)C phases having the following properties: density, 5.3 g/cm3; hardness, 22.9 GPa; fracture toughness, 4.7 MPa m0.5; heat capacity, 0.52 J/(g·K); thermal diffusivity, 11.67 mm2/s; and thermal conductivity, 33.28 W/(m·K).

Biomimetic copper-containing nanogels for imaging-guided tumor chemo-chemodynamic-immunotherapy

Developing multifunctional nanoplatforms to comprehensively modulate the tumor microenvironment and enhance diagnostic and therapeutic outcomes still remains a great challenge. Here, we report the facile construction of a multivariate nanoplatform based on cancer cell membrane (CM)-encapsulated redox-responsive poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) co-loaded with Cu(II) and chemotherapeutic drug toyocamycin (Toy) for magnetic resonance (MR) imaging-guided combination tumor chemodynamic therapy/chemoimmunotherapy. We show that redox-responsive PVCL NGs formed through precipitation polymerization can be aminated, conjugated with 3,4-dihydroxyhydrocinnamic acid for Cu(II) complexation, physically loaded with Toy, and finally camouflaged with CMs. The created ADCT@CM NGs with an average size of 113.0 nm are stable under physiological conditions and can efficiently release Cu(II) and Toy under tumor microenvironment with a high level of glutathione. Meanwhile, the developed NGs are able to enhance cancer cell oxidative stress and endoplasmic reticulum stress by synergizing the effects of chemodynamic therapy mediated by Cu-based Fenton-like reaction and Toy-mediated chemotherapy, thereby triggering significant immunogenic cell death (ICD). In a melanoma mouse model, the NGs show potent immune activation effects to reinforce tumor therapeutic efficacy through ICD induction and immune modulation including high levels of immune cytokine secretion, increased tumor infiltration of CD8+ cytotoxic T cells, and reduced tumor infiltration of regulatory T cells. With the CM coating and Cu(II) loading, the developed NG platform demonstrates homologous tumor targeting and T1-weighted MR imaging, hence providing a general biomimetic NG platform for ICD-facilitated tumor theranostic nanoplatform. Statement of significanceDeveloping multifunctional nanoplatforms to comprehensively modulate the tumor microenvironment (TME) and enhance theranostic outcomes remains a challenge. Here, a cancer cell membrane (CM)-camouflaged nanoplatform based on aminated poly(N-vinylcaprolactam) nanogels (NGs) co-loaded with Cu(II) and toyocamycin (Toy) was prepared for magnetic resonance (MR) imaging-guided combination tumor chemodynamic therapy/chemoimmunotherapy. The tumor targeting specificity and efficient TME-triggered release of Cu(II) and Toy could enhance tumor cell oxidative stress and endoplasmic reticulum stress by synergizing the effects of chemodynamic therapy mediated by Cu-based Fenton-like reaction and Toy-mediated chemotherapy, respectively, thereby leading to significant immunogenic cell death (ICD) and immune response. With the CM coating and Cu(II) loading, the developed NG platform also demonstrates good T1-weighted tumor MR imaging performance. Hence, this study provides a general biomimetic NG platform for ICD-facilitated tumor theranostics.

IoT - Toxic Gas Detection System in Sewage

The application of IoT and machine learning in gas detection systems for sewage offers an innovative approach to real-time gas detection and enhances environmental safety in industrial and urban environments. This system uses advanced technologies such as the Internet of Things (IoT), machine learning algorithms, and high-performance sensors like the MQ135 and the DHT11 to achieve the best results in the gas concentration measurement and collection. It identifies abnormalities and determines which emission control measures are most effective for specific release points and similar situations. The design of the device includes sensor nodes that are primarily responsible for data collection and a central microcontroller (MCU) that operates a machine learning algorithm for efficient anomaly detection and predictive maintenance. The system uses the IoT connection to regularly send data to cloud platform (Blynk), enabling real time monitoring of gas levels and environmental conditions. The system generates a visual image of the captured data that can be accessed online. Distinctive attributes like accurate gas detection, continuous monitoring, predictive maintenance, remote assessment, and comprehensive data visualization, all contribute to smart decision-making for environmental safety.

Intraoperative Cavity Local Delivery System with NETs-Specific Drug Release for Post-Breast Cancer Surgery Recurrence Correction.

Postoperative breast cancer recurrence is tricky due to the limited therapeutic options. Transforming growth factors-β (TGF-β) is vital in promoting postoperative tumor recurrence. However, conventional blocking strategies fail to satisfy both bio-safety and sufficient relapse correction. Neutrophil extracellular traps (NETs) are essential for the spatiotemporal dynamics of TGF-β at tumor-resection sites, whose unique mechanism for local TGF-β amplification could remarkably increase the risk of relapse after surgery. Herein, the principle of NETs formation is ingeniously utilized to construct a surgical residual cavity hydrogel that mimics NETs formation. The hydrogel is prepared based on the electrostatic interaction between histidine (His) and sodium alginate (Alg). Then, arginine deiminase 4 (PAD4) protein is released during NETs formation. Simultaneously, the electrical property of His in hydrogel changes automatically, which further lead to promising localized release of anti-TGF-β. The hydrogel system can realize specific and selective drug release at targeted NETs site over a prolonged period while exhibiting excellent biocompatibility. Superior breast cancer recurrence inhibition is achieved by suppressing TGF-β and related indicators, impeding epithelial-mesenchymal transition (EMT) progression, and rectifying the locally exacerbated immunosuppressive environment within NETs. The novel NETs local microenvironment drug release functional hydrogel will provide inspiration for postoperative recurrence correction strategies.

Kinetic analysis of an optically pumped rare gas lasing medium with a nanosecond repetitively pulsed discharge in Ar-He mixture

A kinetic model of a lasing medium for an optically pumped rare gas laser (OPRGL) was developed that accounts for the production of excited argon atoms Ar* in a nanosecond repetitively pulsed discharge (NRPD). Analytical formulas were derived for the frequency of Ar* radiation losses, population of the energy levels involved in the laser cycle and specific powers for pump absorption and lasing in the limit of bleaching of pump and lasing transitions. The formulas use the kinetic constants of the model as parameters and Ar* number density as the independent variable. Periodic solutions for number density of plasma components, pump absorption and small signal gain, specific pump absorption and lasing were obtained numerically. Mean over the NRPD period values of Ar* number density, specific pump absorption and lasing were calculated as the functions of the preset peak values of the reduced electric field E/N. Triangular electric field pulses of 80 ns FWHM duration and 200 kHz frequency were considered. Optical pumping increases Ar* loss by more than a factor of 10, due to excess spontaneous emission from Ar* levels that populates the 1s4 state of argon, resulting in a reduced NRPD plasma ionization and Ar* production. As a result, without auxiliary optical pumping from the 1s4 state that compensates this loss, the averaged across the discharge period Ar* number density decreases by a factor of 30. Moreover, the average specific heat release in plasma becomes almost equal to the specific lasing power in the acceptable operating modes, making auxiliary optical pumping mandatory for scaling of an OPRGL. The sensitivity of the results to the values of kinetic constants in the model is analyzed.

The comparative performance study of the EF7 downsized engines; fuel economy besides CO2 reduction

Engine downsizing is considered a strategic idea in fuel economy enhancement as well as reduction. It is defined in the literature as the decrease in engine geometrical dimensions besides its performance being fixed. In this research, the Iranian gasoline-fueled national engine, EF7, has been investigated for 25% downsizing. After introducing the gasoline-fueled and CNG-fueled versions of downsized engines, their performance, besides release rates are studied in detail. A one-dimensional engine simulator coupled with a 3D-CFD model is developed to carry out such an investigation, an experimental test setup is provided to evaluate the accuracy of the provided numerical model, as well. The first version of presented downsized engines, called EF7, is a 3-cylinder engine with the same geometrical characteristics as the base engine, which is equipped with a turbo-charger and dual CVVT technologies. The EF7 is then introduced by fuel shifting to CNG as the second version of downsized engines, and finally, increasing the compression ratio, the EF7 is presented as the third version of studied-downsized engines. The results show almost the same rate of BSFC besides a 3.4% reduction in concentration for EF7, 20.6% fuel economy enhancement, besides 20.8% reduction in the specific release rate for EF7, and 28.8% fuel economy enhancement, besides 25.3% reduction in the specific release rate for EF7 in comparison with the base engine.

Applicability of the inverse dispersion method to measure emissions from animal housings

Abstract. Emissions from agricultural sources substantially contribute to global warming. The inverse dispersion method (IDM) has been successfully used for emission measurements from various agricultural sources. The IDM has also been validated in multiple studies with artificial gas releases mostly in open fields. Release experiments from buildings have rarely been conducted and were partly affected by additional nearby sources of the target gas. Specific release studies for naturally ventilated animal housings are lacking. In this study, a known and predefined amount of methane (CH4) was released from an artificial source inside a barn that mimicked a naturally ventilated dairy housing, and IDM recovery rates, using a backward Lagrangian stochastic (bLS) model, were determined. For concentration measurements, open-path devices (OPs) with a path length of 110 m were placed in a downwind direction of the barn at fetches of 2.0h, 5.3h, 8.6h, and 12h (h equals the height of the highest obstacle), and a 3D ultrasonic anemometer (UA) was placed in the middle of the first three OP paths. Upwind of the barn, an additional OP and a UA were installed. The median IDM recovery rates determined with the UA placed upwind of the barn and the downwind OP ranged between 0.55–0.75. It is concluded that, for the present study case, the effect of the building and a tree in the main wind axis led to a systematic underestimation of the IDM-derived emission rate probably due to deviations in the wind field and turbulent dispersion from the underlying assumptions of the used dispersion model.

Potential of Pullulan-Based Polymeric Nanoparticles for Improving Drug Physicochemical Properties and Effectiveness.

This scientific review aims to comprehensively discuss and summarize recent advancements in pullulan-based polymeric nanoparticles, focusing on their formulation, characterization, evaluation, and efficacy. A search on Scopus, PubMed, and Google Scholar, using "Pullulan and Nanoparticle" as keywords, identified relevant articles in recent years. The literature search highlighted a diverse range of studies on the pullulan-based polymeric nanoparticles, including the success of high-selectivity hybrid pullulan-based nanoparticles for efficient boron delivery in colon cancer as the active targeting nanoparticle, the specific and high-efficiency release profile of the development of hyalgan-coated pullulan-based nanoparticles, and the design of multifunctional microneedle patches that incorporated pullulan-collagen-based nanoparticle-loaded antimicrobials to accelerate wound healing. These studies collectively underscore the versatility and transformative potential of pullulan-based polymeric nanoparticles in addressing biomedical challenges. Pullulan-based polymeric nanoparticles are promising candidates for innovative drug delivery systems, with the potential to overcome the limitations associated with traditional delivery methods.

Exploring Nanohydrogels: Crafting Innovations for Biomedical Advancements

AbstractHere in, we discuss different types of nanohydrogels in the field of biomedicine, highlighting their unique properties such as size, biocompatibility, and tuneable drug release capabilities. Nanohydrogels are considered versatile tools for applications in tissue engineering, drug delivery, and diagnostics, with the ability to target specific sites and release therapeutic agents in a controlled manner. The controlled‐release characteristics of nanohydrogels are particularly emphasized for targeted drug delivery, potentially transforming therapies for conditions like cancer by maximizing treatment efficacy while minimizing damage to healthy tissues. Several research articles published on nanohydrogels has been steadily increasing over the years, indicating growing interest and research activity in this field. This review provides an overview of contemporary methodologies employed in nanohydrogel design, their utilization in biomedical contexts, and their pivotal role in shaping advanced therapeutics. Recent investigations on nanohydrogels are scrutinized for their extensive utility in devising strategies conducive to finely tuned biological applications. Challenges and obstacles associated with the nanohydrogel technology in biomedicine also has been discussed. Cautious handling of the interaction of nanohydrogels with complex biological systems is also emphasized for the successful integration of this technology into medical applications.

Targeted redox-responsive peptide for arterial chemoembolization therapy of orthotropic hepatocellular carcinoma

ObjectiveTranscatheter Arterial Chemoembolization (TACE) is the first choice for the treatment of advanced-stage hepatocellular carcinoma (HCC). However, TACE suffers from a lack of specificity and rapid drug release. Herein, a targeted redox-responsive peptide (TRRP) was synthesized and used as a carrier of doxorubicin (DOX) to enhance the efficacy of TACE through tumor cells targeting and controlled drug release.MethodsTRRP has a high loading capacity of DOX and a sensitive drug release behavior at high glutathione (GSH) concentration. Moreover, TRRP could bind to the transferrin receptor on the surface of tumor cells, which enhanced the efficacy of TACE and reduced side effects of TACE. TACE with TRRP@DOX dispersed in lipiodol shows an enhanced therapeutic outcome compared to the treatment with DOX + lipiodol emulsion in orthotopic rat HCC models.ResultsTRRP has a high loading capacity of DOX and a sensitive drug release behavior at GSH concentration. Moreover, TRRP could bind to the transferrin receptor on the surface of tumor cells, which enhanced the efficacy of TACE and reduced side effects of TACE. TACE with TRRP@DOX dispersed in lipiodol shows an enhanced therapeutic outcome compared to the treatment with DOX + lipiodol emulsion in orthotopic rat HCC models.ConclusionsThis study demonstrated that TRRP was a promising therapeutic agent for enhancing TACE therapy for HCC treatment.Graphical abstract

In silico-guided discovery and in vitro validation of novel sugar-tethered lysinated carbon nanotubes for targeted drug delivery of doxorubicin

ContextMultiwalled carbon nanotubes (MWCNTs) functionalized with lysine via 1,3-dipolar cycloaddition and conjugated to galactose or mannose are potential nanocarriers that can effectively bind to the lectin receptor in MDA-MB-231 or MCF-7 breast cancer cells. In this work, a method based on molecular dynamics (MD) simulation was used to predict the interaction of these functionalized MWCNTs with doxorubicin and obtain structural evidence that allows a better understanding of the drug loading and release process. The MD simulations showed that while doxorubicin only interacted with pristine MWCNTs through π-π stacking interactions, functionalized MWCNTs were also able to establish hydrogen bonds, suggesting that the functionalized groups improve doxorubicin loading. Moreover, the elevated adsorption levels observed for functionalized nanotubes further support this enhancement in loading efficiency. MD simulations also shed light on the intratumoral pH-specific release of doxorubicin from functionalized MWCNTs, which is induced by protonation of the daunosamine moiety. The simulations show that this change in protonation leads to a lower absorption of doxorubicin to the MWCNTs. The MD studies were then experimentally validated, where functionalized MWCNTs showed improved dispersion in aqueous medium compared to pristine MWCNTs and, in agreement with the computational predictions, increased drug loading capacity. Doxorubicin-loaded functionalized MWCNTs demonstrated specific release of doxorubicin in tumor microenvironment (pH = 5.0) with negligible release in the physiological pH (pH = 7.4). Furthermore, doxorubicin-free MWNCT nanoformulations exhibited insignificant cytotoxicity. The experimental studies yielded nearly identical results to the MD studies, underlining the usefulness of the method. Our functionalized MWCNTs represent promising non-toxic nanoplatforms with enhanced aqueous dispersibility and the potential for conjugation with ligands for targeted delivery of anti-cancer drugs to breast cancer cells.MethodsThe computational model of a pristine carbon nanotube was created with the buildCstruct 1.2 Python script. The lysinated functionalized groups were added with PyMOL and VMD. The carbon nanotubes and doxorubicin molecules were parameterized using the general AMBER force field, and RESP charges were determined using Gaussian 09. Molecular dynamics simulations were carried out with the AMBER 20 software package. Adsorption levels were calculated using the water-shell function of cpptraj. Cytotoxicity was evaluated via a MTT assay using MDA-MB-231 and MCF-7 breast cancer cells. Drug uptake of doxorubicin and doxorubicin-loaded MWCNTs was measured by fluorescence microscopy.

Designing pH-Responsive alizarin hybrids with easily tunable physicochemical properties via polymer grafting

This study focuses on the synthesis and characterization of novel pH-sensitive color materials based on alizarin, (1,2-dihydroxyanthraquinone), a natural pigment with versatile properties. The polymer-based indicators were prepared by grafting poly(methyl methacrylate) (PMMA) and poly(2-hydroxyethyl methacrylate) (PHEMA) from alizarin through an ester pH-liable bond, allowing for easy tunability of their physicochemical properties. The synthesis process involved the esterification of alizarin using 2-bromo-2-methylpropionyl bromide, facilitated by triethylamine as an acid scavenger. The resulting alizarin served as a difunctional initiator for atom transfer radical polymerization (ATRP) of methyl methacrylate and 2-hydroxyethyl methacrylate. The molecular structures of the synthesized hybrids were confirmed using 1H NMR and GPC analyses. The color characteristic, surface energy, thermal stability, and pH sensing activity of the alizarin-based hybrids were studied according to the type of grafted polymer nature as well as their degree of polymerization. PHEMA-grafted alizarin showed more rapid and more visible color changes under the influence of NH3 vapours compared to PMMA hybrids, due to their less hydrophobic nature. Furthermore, kinetic plots demonstrated various hydrolysis rates, with PMMA hydrolysis being slower than that of PHEMA due to its stronger hydrophobic character. UV–Vis spectra and GPC traces confirmed the occurrence of hydrolysis and successful cleavage of the ester bond links between the grafted polymers and alizarin with a decrease of the molar mass by a factor of two as expected. Such behavior offers opportunities for tailoring degradation profiles and achieving specific release profiles upon application of a wide range of polymers with varied character. The designed polymer-based pigments exhibited a high ability to monitor calorimetrically the pH changes, especially in alkaline conditions. Overall, this study contributes to the broadening of the application of alizarin-based materials, paving the way for further exploration and development in the field of functional materials.