Circulation Time Research Articles

Targeting of Low-Immunogenic Poly(ethylene glycol) Nanoparticles for Photothermal-Enhanced Immunotherapy.

The assembly of low-immunogenic poly(ethylene glycol) nanoparticles (PEG NPs) for targeted delivery of therapeutics (i.e., mitoxantrone and imidazoquinoline) and improved photothermal-immunotherapy is reported. The targeted PEG NPs incorporating targeting molecules of hyaluronic acid are engineered via the templating of metal-organic frameworks, which can circumvent accelerated blood clearance and exhibit prolonged circulation time as well as improved accumulation of therapeutics at tumor sites. The targeted delivery of mitoxantrone under laser radiation induces immunogenic cell death of tumor cells, which is combined with toll-like receptor 7/8 agonists of imidazoquinoline to trigger immune responses of cytotoxic T lymphocytes for the eradication of tumor cells. Furthermore, the treatment can induce tumor-specific immune responses that inhibit metastatic lung tumor growth. This reported targeted PEG NPs provide a rational design for cancer immunotherapy.

Precisely Tailoring Molecular Structure of Doxorubicin Prodrugs to Enable Stable Nanoassembly, Rapid Activation, and Potent Antitumor Effect.

Achieving a balance between stable drug loading/delivery and on-demand drug activation/release at the target sites remains a significant challenge for nanomedicines. Carrier-free prodrug nanoassemblies, which rely on the design of prodrug molecules, offer a promising strategy to optimize both drug delivery efficiency and controlled drug release profiles. A library of doxorubicin (DOX) prodrugs was created by linking DOX to fatty alcohols of varying chain lengths via a tumor-responsive disulfide bond. In vitro studies assessed the stability and drug release kinetics of the nanoassemblies. In vivo studies evaluated their drug delivery efficiency, tumor accumulation, and antitumor activity in mouse models. In vitro results demonstrated that longer fatty alcohol chains improved the stability of the nanoassemblies but slowed down the disassembly and drug release process. DSSC16 NAs (hexadecanol-modified DOX prodrug) significantly prolonged blood circulation time and enhanced tumor accumulation, with AUC values 14.2-fold higher than DiR Sol. In 4T1 tumor-bearing mouse models, DSSC16 NAs exhibited notably stronger antitumor activity, resulting in a final mean tumor volume of 144.39 ± 36.77 mm3, significantly smaller than that of all other groups (p < 0.05 by ANOVA at a 95% confidence interval). These findings underscore the critical role of prodrug molecule design in the development of effective prodrug nanoassemblies. The balance between stability and drug release is pivotal for optimizing drug delivery and maximizing therapeutic efficacy.

Synergistic Therapy of Metastatic Breast Cancers by Biomimetic Chemotherapeutic Drug-Gene Nanoparticles.

Cancer metastasis is responsible for more than 90% of tumor-related deaths. Especially, metastatic breast cancer (MBC) is a common malignancy with a high mortality among women worldwide. It is urgent to develop effective drugs for the treatment of MBC. Herein, biomimetic chemotherapeutic drug-gene nanoparticles (named TPT-ASOVEGF@MM NPs) were constructed for the combination therapy of MBC. First, topotecan hydrochloride (TPT) and vascular endothelial growth factor antisense oligonucleotide (ASOVEGF) were coself-assembled in water through electrostatic interaction to produce chemotherapeutic drug-gene nanoparticles (TPT-ASOVEGF NPs). Then, the nanoparticles were encapsulated within macrophage membranes (MM) to form biomimetic TPT-ASOVEGF@MM NPs with long circulation time in blood and active tumor-targeting ability. TPT-ASOVEGF@MM NPs can be effectively internalized by breast cancer cells and then the nanoparticles collapse to simultaneously release TPT and ASOVEGF. ASOVEGF can inhibit the expression of VEGF, impeding the process of neovascularization and blocking the metastatic pathway of cancer cells. Meanwhile, TPT can bind to the topoisomerase I-DNA complex to prevent DNA repair and replication, and further induce apoptosis of cancer cells. In addition, TPT can also affect hypoxia-inducible factor 1α (HIF-1α) expression and inhibit hypoxia-induced tumor metastasis to achieve synergistic therapy with ASOVEGF. In MBC mouse models, the in vivo inhibition rate of TPT-ASOVEGF@MM NPs for lung metastasis was 89.5%, with minor toxic side effects and the least number of metastatic nodules in the lungs. In summary, TPT-ASOVEGF@MM NPs would be a promising biomimetic nanodrug for chemo-gene combination therapy of MBC with high efficacy and safety in clinics.

New Perspectives on the Function of Han Dynasty Gold Products with a Focus on the Unearthed Gold from the Tomb of the Marquis of Haihun

This study focuses on the "Mati Jin" among the gold artifacts of ancient China's Han Dynasty, exploring its significant role and profound influence on social culture, economy, and politics. By integrating archaeological discoveries and historical documents, the study aims to understand the form, production, circulation, and cultural significance of "Mati Jin". The research finds that there are distinct differences in form and use between "Mati Jin" and "Lin Zhi Jin", and the production techniques and circulation time of "Mati Jin" span from the Warring States period to the Han Dynasty. Moreover, "Mati Jin" is not only a reward for vassal kings but also has multiple functions such as currency circulation, storage means, and contributions. With the continuous advancement of archaeological technology and the emergence of new discoveries, new perspectives and evidence have been provided for the study of "Mati Jin", promoting a deeper understanding in the academic community.

Isoquercitrin Loaded PEGylated Long Circulating Liposomes Improve Bone Mass and Reduce Oxidative Stress After Osteoporosis.

Osteoporosis has increasingly become a major public health concern because of its associated heightened risk of bone fragility and fractures. In order to avoid the adverse risk of hormone therapy, scientists have considered isoquercitrin (IQ) as a natural phytoestrogen to potentially prevent osteoporosis. However, IQ has poor solubility and bioavailability which culminates in rapid elimination of phytoestrogen. Herein, this study sought to solve limited applications of IQ by preparing IQ-loaded PEGylated long circulating liposomes (IQ-Lips) via thin-film hydration method. After appropriate characterization using zeta-potential, polydispersed index (PDI), particle size and entrapment efficiency (EE), IQ-Lips were applied to ovariectomized rat models to evaluate their effect on osteoporosis. The results showed that the prepared IQ-Lips exhibited smaller sized nanoparticles (125.35 ± 4.50nm), excellent PDI (0.244 ± 0.001) and zeta-potential (-28.64 ± 0.71 mV) with stable property and higher EE (92.10 ± 0.32%). Importantly, administration of IQ-Lips through oral route increased aqueous solvability, bioavailability and circulation time of IQ. Moreover, the IQ-Lips could increase bone microstructural densities and bone mass, as well as reduce oxidative stress in ovariectomized rat models. Altogether, the IQ-Lips may serve as a novel avenue to potentially prolong the circulation of IQ in the body and improve the bioavailability of IQ for treatment of osteoporosis.

Improving dexamethasone drug loading and efficacy in treating rheumatoid arthritis via liposome: Focusing on inflammation and molecular mechanisms.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 0.46% of the global population. Conventional therapeutics for RA, including disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, frequently result in unintended adverse effects. Dexamethasone (DEX) is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties. Liposomal delivery of DEX, particularly when liposomes are surface-modified with targeting ligands like peptides or sialic acid, can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity. This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA. Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models, reduces joint inflammation and damage, and alleviates cartilage destruction compared to free DEX. The liposomal formulation also shows better hemocompatibility, fewer adverse effects on body weight and immune organ index, and a longer circulation time with higher bioavailability. The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) and B-cell-activating factor (BAFF), which are key players in the pathogenesis of RA. Additionally, liposomal DEX can induce the expression of anti-inflammatory cytokines like interleukin-10 (IL-10), which has significant anti-inflammatory and immunoregulatory properties. The findings suggest that liposomal DEX represents a promising candidate for effective and safe RA therapy, with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.

Plasma Protein Adsorption on Melphalan Prodrug Bearing Liposomes - Bare, Stealth, and Targeted

Background: Plasma protein binding is inevitable for nanomaterials injected into blood circulation. For liposomes, this process is affected by the lipid composition of the bilayer. Membrane constituents and their ratio define liposome characteristics, namely, surface charge and hydrophobicity, which drive protein adsorption. Roughly 30 years ago, the correlation between the amount of bound proteins and the resulting circulation time of liposomes was established by S. Semple, A. Chonn, and P. Cullis. Here, we have estimated ex vivo plasma protein binding, primarily to determine the impact of melphalan prodrug inclusion into bilayer on bare, PEGylated (stealth), and Sialyl Lewis X (SiaLeX)-decorated liposomes. Experimental: Liposomes were allowed to bind plasma proteins for 15 minutes, then liposome-protein complexes were isolated, and protein and lipid quantities were assessed in the complexes. In addition, the uptake by activated HUVEC cells was evaluated for SiaLeX-decorated liposomes. Results:: Melphalan moieties on the bilayer surface enrich protein adsorption compared to pure phosphatidylcholine sample. Although PEG-lipid had facilitated a significant decrease in protein adsorption in the control sample, when prodrug was added to the composition, the degree of pro-tein binding was restored to the level of melphalan liposomes without a stealth barrier. A similar effect was observed for SiaLeX-decorated liposomes. Conclusion: None of the compositions reported here should suffer from quick elimination from circulation, according to the cut-off values introduced by Cullis and colleagues. Nevertheless, the amount of bound proteins is sufficient to affect biodistribution, namely, to impair receptor recog-nition of SiaLeX and reduce liposome uptake by endothelial cells.

Development of hemoglobin microbubbles for acoustic blood oxygen sensing: A study on PEGylation and gas core modification for in vivo applications.

The creation of innovative ultrasound contrast agents (UCAs) with the ability to monitor oxygen levels in real-time holds immense potential for advancing early diagnosis of various medical conditions such as hypoxic/reperfusion injury. In this study, we propose the development of oxygen sensitive UCAs using microbubbles composed of hemoglobin (HbMBs), which can function as sensors for blood oxygen levels. Previously, we performed a study highlighting the initial proof-of-concept efficacy of air-filled HbMBs in detecting oxygenation changes in vitro, offering a promising tool for clinically detecting tissue hypoxia. Nevertheless, a significant drawback of this approach is the potential for immune reactions and toxicity when hemoglobin is outside its natural red blood cell environment. Moreover, in vitro, HbMBs had low stability, with more than 90% decrease in their concentration after 120 minutes. Therefore, careful consideration of the surface properties and the gas core of HbMBs is crucial. Here, we formulated PEGylated HbMBs (PHbMBs), and investigated their stability, immunogenicity, and their acoustic response in oxygenated and deoxygenated media in vitro. We optimized PEGylated HbMBs (PHbMBs), showing a 42% reduction in immunogenicity and significantly improved stability in vitro, while maintaining their oxygen-binding and acoustic response. In vivo, PHbMBs demonstrated similar contrast enhancement to that of non-PEGylated MBs, demonstrating that PEGylation does not decrease HbMBs' acoustic signaling. Finally, changing the gas core from air to PFB increased PHbMBs' mean circulation time more than 11-fold, without diminishing their responsiveness to oxygen. Overall, the proposed oxygen sensitive PHbMBs offer a promising avenue for real-time acoustic detection of blood oxygen levels, paving the way for potential clinical applications in monitoring critically ill patients. STATEMENT OF SIGNIFICANCE: This research explores the emergent field of Acoustic Oxygen Imaging in vivo using hemoglobin-based microbubbles. This innovative contrast agent approach involves imaging using crosslinked biomaterial comprised of the hemoglobin protein, aiming to transform the way we monitor blood oxygen levels with ultrasound. This work fundamentally addresses central concerns of improving bubble stability and circulation life for eventual clinical use, while minimizing toxicity. Importantly, we demonstrate that PEGylation of hemoglobin microbubbles enhances their stability, reduces immunogenicity, and maintains acoustic responsiveness. The incorporation of perfluorobutane into the bubble core increases the longevity of these microbubbles in circulation, while sustaining their oxygen sensitivity. Favorable in vivo results highlight the potential of this technology in real-time acoustic detection of blood oxygen levels.

Anionic polysaccharides as delivery carriers for cancer therapy and theranostics: An overview of significance.

Recently, cancer therapy has witnessed remarkable advancements with a growing focus on precision medicine and targeted drug delivery strategies. The application of anionic polysaccharides has gained traction in various drug delivery systems. Anionic polysaccharides have emerged as promising delivery carriers in cancer therapy and theranostics, offering numerous advantages such as biocompatibility, low toxicity, and the ability to encapsulate and deliver therapeutic agents to tumor sites with high specificity. This review underscores the significance of anionic polysaccharides as essential components of the evolving landscape of cancer therapy and theranostics. These polymers can be tailored to carry a wide range of therapeutic cargo, including chemotherapeutic agents, nucleic acids, and imaging agents. Their negative charge enables electrostatic interactions with positively charged drugs and facilitates the formation of stable nanoparticles, liposomes, or hydrogels for controlled drug release. Additionally, their hydrophilic nature aids in prolonging circulation time, reducing drug degradation, and minimizing off-target effects. Besides, some of them could act as targeting agents or therapeutic compounds that lead to improved therapeutic performance. This review offers valuable information for researchers, clinicians, and biomedical engineers. It provides insights into the recent progress in the applications of anionic polysaccharide-based delivery platforms in cancer theranostics to transform patient outcomes.

Polyphenol-mediated assembly of toll-like receptor 7/8 agonist nanoparticles for effective tumor immunotherapy.

Toll-like receptor (TLR) 7/8 agonists have shown significant potential in tumor immunotherapy. However, the limited pharmacokinetic properties and systemic toxicity resulting from off-target effects limits their biomedical applications. We here report the polyphenol-mediated assembly of resiquimod (R848, a TLR7/8 agonist) nanoparticles (RTP NPs) to achieve tumor-selective immunotherapy while avoiding systemic adverse effects. Upon intravenous administration, the prepared RTP NPs are effectively accumulated at tumor sites, which increase their bioavailability and reduce systemic inflammation. RTP NPs can trigger a potent antitumor immune response in a mouse tumor model to inhibit tumor growth. Additionally, after subcutaneous injection at the tail base, RTP NPs efficiently migrate to the lymph nodes, where they elicit immune memory to prevent tumorigenesis. This study underscores the potential application of polyphenol-mediated assembly in developing nanomedicines with reduced toxicity for tumor-specific immunotherapy. STATEMENT OF SIGNIFICANCE: Toll-like receptor agonist (R848) nanoparticles for tumor-selective immunotherapy were synthesized through polyphenol-mediated assembly, a method that simplifies preparation process and minimizes potential side effects. Intravenously administered these nanoparticles effectively extended circulation time, enhanced tumor enrichment, and reduced systemic inflammation, thus augmenting the bioavailability and minimizing the side effects of R848. The nanoparticles significantly inhibited tumor growth by triggering a potent antitumor immune response, including dendritic cell maturation, macrophage polarization, T-cell infiltration, and cytokine secretion. Moreover, after subcutaneous injection at the tail base, they can elicit immune memory to prevent tumorigenesis.

Shortened Cerebral Circulation Time Predicts Resistance to Obliteration in High-Flow Brain Arteriovenous Malformations After Stereotactic Radiosurgery.

Treatment selection for brain arteriovenous malformations (BAVMs) is complicated by BAVM size, location, and hemodynamics. Quantitative digital subtraction angiography is used to quantify the hemodynamic impact of BAVMs on cerebral circulation. This study investigated the association between cerebral circulation time and the complete obliteration (CO) rate of BAVMs after stereotactic radiosurgery (SRS). We analyzed the data of 143 patients who underwent SRS for BAVMs between January 2011 and December 2019 in our institute. Their pre-SRS magnetic resonance imaging and angiography images were analyzed to acquire BAVM characteristics and quantitative digital subtraction angiography parameters. Modified cerebral circulation time (mCCT) was defined as the time difference between the bolus arrival time of the ipsilateral cavernous internal carotid artery and that of the parietal vein, as determined from the lateral view of images obtained using digital subtraction angiography. Cox regression with hazard ratios and Kaplan-Meier analyses were conducted to determine the associations between the parameters and BAVM CO after SRS. Of the 143 patients, 101 (70.6%) achieved BAVM CO. According to the multivariate analyses, an increased mCCT (hazard ratio: 1.24, P = .041) was the independent factor associated with BAVM CO after adjustment for age, sex, hemorrhagic presentation, a BAVM volume of >5 cm 3 , and a margin dose of >18 Gy. Individuals with an mCCT of ≤2.32 s had a lower 36-month probability of BAVM CO than did those with an mCCT of >2.32 s (44.1% ± 6.8% vs 63.3% ± 5.6%, P = .034). The hemodynamic impact of high-flow BAVM demonstrated by a shortened mCCT is associated with a lower BAVM CO rate after SRS.

Nanotechnology-Based Drug Delivery Systems for Chemotherapy: A Review of Current Approaches and Future Prospects

Nanotechnology-based drug delivery systems have developed as a novel approach to cancer treatment, notably chemotherapy, with higher precision, efficacy, and less side effects than traditional approaches. Chemotherapy, while successful in targeting rapidly dividing cancer cells, frequently encounters considerable hurdles such as systemic toxicity, non-targeted drug distribution, and resistance. Nanotechnology offers a promising alternative for targeted delivery, controlled release, and overcoming multidrug resistance (MDR). Various nanocarriers, such as liposomes, polymeric nanoparticles, dendrimers, and metallic nanoparticles, have been developed to improve drug delivery by leveraging the increased permeability and retention (EPR) effect for tumour targeting. The design of these nanocarriers, which includes size, surface qualities, and functionality, provides longer circulation time, increased tumour formation, and fewer side effects on healthy tissues. Despite multiple clinical achievements, such as the FDA's clearance of nanomedicines like Doxil and Abraxane, there are still obstacles in translating these technologies from laboratory research to clinical practice. Nanoparticle stability, scalability, regulatory barriers, and cytotoxicity are all important considerations. This study examines the current state of nanotechnology-based drug delivery systems, emphasizing clinical accomplishments, problems, and upcoming technologies such as stimuli-responsive and AI-assisted drug delivery systems. The future of cancer treatment is in the creation of smart nanocarriers that can combine chemotherapy with other therapeutic modalities such as immunotherapy, gene therapy, and photodynamic therapy. Hence, personalized nanomedicine, which tailors drug delivery systems to individual patients' genetic profiles and tumour features, is a promising future direction. Overall, this review seeks to investigate the most recent developments and future prospects in nanotechnology-driven chemotherapy.

Nanomaterials‐Induced PANoptosis: A Promising Anti‐Tumor Strategy

AbstractMalignant tumors pose a significant threat to global public health. Promoting programmed cell death in cancer cells has become a critical strategy for cancer treatment. PANoptosis, a newly discovered form of regulated cell death, integrates key molecular components of pyroptosis, apoptosis, and necroptosis, activating these three death pathways simultaneously to achieve synergistic multi‐mechanistic killing. PANoptosis significantly inhibits cancer cell growth and resistance and activates strong anti‐tumor immune response, making tumor‐specific induction of PANoptosis a potential cancer therapeutic strategy. Currently, cancer treatment research related to PANoptosis is focused mainly on the development of small molecules and cytokines. However, these approaches still face limitations in terms of metabolic stability and tumor specificity. The unique physicochemical properties and biological activities of nanomaterials hold significant promise for optimizing PANoptosis induction strategies. This review summarizes the concept and mechanisms of PANoptosis, highlights the latest applications of nanoagents in PANoptosis‐based anti‐cancer therapy, and discusses the challenges and future directions for clinical translation. It is hoped that this review will inspire further exploration and development of PANoptosis‐based cancer treatments, providing new perspectives for researchers in the field.

Nanomaterials-Induced PANoptosis: A Promising Anti-Tumor Strategy.

Malignant tumors pose a significant threat to global public health. Promoting programmed cell death in cancer cells has become a critical strategy for cancer treatment. PANoptosis, a newly discovered form of regulated cell death, integrates key molecular components of pyroptosis, apoptosis, and necroptosis, activating these three death pathways simultaneously to achieve synergistic multi-mechanistic killing. PANoptosis significantly inhibits cancer cell growth and resistance and activates strong anti-tumor immune response, making tumor-specific induction of PANoptosis a potential cancer therapeutic strategy. Currently, cancer treatment research related to PANoptosis is focused mainly on the development of small molecules and cytokines. However, these approaches still face limitations in terms of metabolic stability and tumor specificity. The unique physicochemical properties and biological activities of nanomaterials hold significant promise for optimizing PANoptosis induction strategies. This review summarizes the concept and mechanisms of PANoptosis, highlights the latest applications of nanoagents in PANoptosis-based anti-cancer therapy, and discusses the challenges and future directions for clinical translation. It is hoped that this review will inspire further exploration and development of PANoptosis-based cancer treatments, providing new perspectives for researchers in the field.

Gallium-68 Labeled Positron Emission Computed Tomography Tracer Targeting Glypican-3 with High Contrast for Hepatocellular Carcinoma Imaging.

Hepatocellular carcinoma (HCC) represents the predominant form of primary liver cancer, yet early, precise, and noninvasive detection continues to pose a considerable clinical challenge. Glypican-3 (GPC3), a membrane-bound proteoglycan, is markedly overexpressed in most HCC cases, while exhibiting low expression in normal and hepatitis-affected liver tissues. Given its crucial role in malignant transformation and tumor progression, GPC3 emerges as a compelling target for imaging. In this study, we developed and evaluated 2 68Ga-labeled GPC3-targeted positron emission tomography (PET) probes, each incorporating either polyethylene glycol (PEG) or 4-(p-methylphenyl)butanoic acid (an albumin-binding moiety). Comparative analyses revealed that 68Ga-ALB-GBP, which includes the albumin-binding moiety, exhibited superior in vivo stability, enhanced tumor uptake, and an improved tumor-to-liver ratio relative to 68Ga-PEG2-GBP in subcutaneous HCC mouse models. Micro-PET/computed tomography imaging of orthotopic liver cancer with 68Ga-ALB-GBP demonstrated a tumor-to-liver ratio of 2.29 ± 0.13 and a tumor-to-muscle ratio of 13.03 ± 1.63 at 3 h postinjection, outperforming the performance of the clinically used 18F-fluorodeoxyglucose PET imaging. These findings suggest that 68Ga-ALB-GBP is a promising diagnostic tool for HCC and a strong candidate for clinical translation with potential utility in both diagnostic and therapeutic settings. Moreover, the incorporation of an albumin-binding moiety into PET tracers significantly extends blood circulation time, thereby enhancing bioavailability and facilitating high-contrast PET imaging.

99mTc-Labeled D-Type PTP as a Plectin-Targeting Single-Photon Emission Computed Tomography Probe for Hepatocellular Carcinoma Imaging.

Plectin, a scaffolding protein overexpressed in tumor cells, plays a significant role in hepatocellular carcinoma (HCC) proliferation, invasion, and migration. However, the use of L-type peptides for targeting plectin is hindered by their limited stability and retention. We designed a D-type plectin-targeting peptide (DPTP) and developed a novel single-photon emission computed tomography (SPECT) probe for HCC imaging. The DPTP targeting ability was evaluated in vitro using flow cytometry and ex vivo fluorescence imaging. 99mTc radiolabeling was performed using tricine and ethylenediamine-N,N'-diacetic acid (EDDA) as coligands after modification with 6-hydrazino nicotinamide (HYNIC) at the N termini of DPTP. The radiochemical purity (RCP), in vitro stability, and binding affinity of the prepared 99mTc-HYNIC-DPTP were analyzed. Tumor uptake, metabolic stability, biodistribution, and pharmacokinetics of 99mTc-HYNIC-DPTP were investigated and compared with those of 99mTc-labeled L-type PTP (99mTc-HYNIC-PTP) in HCC tumor-bearing mice. DPTP could be efficiently radiolabeled with 99mTc using the HYNIC/tricine/EDDA system with a high RCP and good in vitro stability. Compared with the L-type PTP, DPTP exhibited improved targeting ability, and 99mTc-HYNIC-DPTP displayed higher tumor uptake, better metabolic stability, longer blood circulation time, and lower kidney retention, resulting in superior imaging performance and biodistribution in vivo. 99mTc-HYNIC-DPTP has great potential as a novel SPECT probe for diagnosing HCC.

Cilostazol Alleviates Delayed Cerebral Ischemia After Subarachnoid Hemorrhage by Attenuating Microcirculatory Dysfunction.

Cilostazol, a phosphodiesterase 3 (PDE3) inhibitor that exerts antiplatelet effects, has therapeutic potential for delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, its mechanism of action remains unclear. We hypothesized that cilostazol alleviates DCI by improving cerebral microcirculatory dysfunction, which is a component of early brain injury. To test this hypothesis, we analyzed the intracerebral circulation time (iCCT) in 256 patients with aSAH from two randomized controlled trials (74 received cilostazol, 54 received pitavastatin, and 128 were controls). A minority of patients (n = 72, 28%) developed severe angiographic vasospasm (aVS) and DCI (n = 42, 16%) and had poor outcomes (n = 35, 14%). We measured iCCT as the time to peak in the ultraearly phase (baseline) and the subacute phase or at DCI onset (follow-up). The cilostazol group had shorter follow-up iCCT and larger iCCT differences than the other groups, indicating improved microcirculatory function, particularly in patients with DCI and poor outcomes. Multivariate analysis revealed that cilostazol treatment is a significant predictor of favorable outcomes, whereas DCI occurrence, a decrease in iCCT differences, and high clinical severity (Hunt & Hess grades 3-4) were associated with poor outcomes. Diminished microcirculatory dysfunction may alleviate DCI and improve outcomes among patients with aSAH following cilostazol treatment. Further research is warranted to confirm these findings and explore the dose-dependent effects of cilostazol on the microcirculatory function.

Advances in cancer diagnosis and therapy by alginate-based multifunctional hydrogels: A review

The field of oncology has been changed by the application of hydrogels. These 3D polymeric networks have demonstrated significant promise in the treatment of cancer and can boost the efficacy of conventional therapeutics including chemotherapy and immunotherapy. Noteworthy, the development of biocompatible and effective hydrogels has been of interest. In this case, alginate as a biopolymer and carbohydrate polymer has been used to modify or synthesis multifunctional nanoparticles for the treatment of human diseases, especially cancer. Therefore, highlighting the function of alginate in the development of hydrogels in cancer therapy can provide new insights for improving outcome and survival rate of patients. Alginate hydrogels improve the specific and selective delivery of cargo and therefore, they reduce the systemic toxicity of drugs, while they enhance anti-cancer activity. Alginate hydrogels protect the genes against degradation by enzymes and increase blood circulation time. The alginate hydrogels can respond to the specific stimuli in the tumor microenvironment including pH, redox and light to improve the site-specific release of cargo. The nanoparticles can be incorporated in the structure of alginate hydrogels to augment their anti-cancer activity. In addition, alginate hydrogels can accelerate immunotherapy and phototherapy through delivery of immunomodulators and photosensitizers, respectively.

Brief Comparison of the Efficacy of Cationic and Anionic Liposomes as Nonviral Delivery Systems.

In recent decades, the development and application of nonviral vectors, such as liposomes and lipidic nanoparticles, for gene therapy and drug delivery have seen substantial progress. The interest in the physicochemical properties and structures of the complexes liposome/DNA and liposome/RNA is due to their potential to substitute viruses as carriers of drugs or genetic material into cells with minimal cytotoxicity, which could lead to their use in gene therapy. Initially, cationic liposomes were utilized as nonviral DNA delivery vectors; subsequently, different molecules, such as polymers, were incorporated to enhance transfection efficiency. Additionally, liposome/protein complexes have been developed as nonviral vectors for the treatment of diseases. The most relevant internalization pathways of these vectors and the few transfection results obtained using targeted and nontargeted liposomes are discussed below. The high cytotoxicity of cationic liposomes represents a significant challenge for the development of gene therapy and drug delivery. Anionic liposomes offer a promising alternative to address the limitations of conventional cationic liposomes, including immune response, short circulation time, and low toxicity. This review will discuss the advantages of cationic liposomes and the novel anionic liposome-based systems that have emerged as a result. The advent of novel designs and manufacturing techniques has facilitated the development of innovative systems, designated as lipid nanoparticles (LNPs), which serve as highly efficacious regulators of the immune system.

Methyl ester production process from palm fatty acid distillate using hydrodynamic cavitation reactors in series with solid acid catalyst

This study aims to optimize the reduction of free fatty acids (FFAs) in palm fatty acid distillate (PFAD) using hydrodynamic cavitation reactors (HCRs) in series and a solid acid catalyst for biodiesel production. Hydrodynamic cavitation is used to accelerate the esterification of FFAs using a heterogeneous acid catalyst. There are three HCRs units, and each HCR composed of a 3D-printed rotor and stator, is separated by flanges and equipped with a basket for holding Amberlyst-15 catalyst. Through response surface methodology (RSM), the esterification process is optimized by adjusting its optimal parameters, namely, methanol (2–12 wt%), circulation time (30–170 min), and rotor speed (1000–3000 rpm). The optimal conditions for achieving a maximum methyl ester purity of 89.76 wt% in converting FFA in first-step esterified oil are 9 wt% methanol (molar ratio of methanol to oil of 4:1), 133 min of circulation time, and 2000 rpm of rotor speed. An 82.48 wt% biodiesel yield is achieved from the HCRs in series under the optimal conditions. Scanning electron microscope images reveal that after the esterification process, there are minor cracks and defects on the catalyst’s resin surface, indicating the presence of residual reactants. Further examination of the catalyst after the esterification process, reveals an average absorption pore diameter of 341.41 Å and BET surface area of approximately 41.68 m2/g. Although there were slight physical changes in the catalyst, HCRs technology offers a viable FFA reduction process that could enhance biodiesel production efficiency. Moreover, the optimized conditions achieved in this study contribute to the advancement of biodiesel production processes and provide insights into the performance of the catalyst used.