Molecular Pharmaceutics最新文献

{"title":"Voices in <i>Molecular Pharmaceutics</i>: Meet Dr. Thomas Waigh, a Physicist Probing the Intricacies of Monoclonal Antibody Rheology.","authors":"Thomas A Waigh","doi":"10.1021/acs.molpharmaceut.5c01295","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c01295","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Study of the PSMA-Targeting Fluorescent and PET Imaging Tracer [68Ga]Ga-NYM036 for Prostate Cancer Diagnosis and Surgical Navigation","authors":"Yu Zhang,&nbsp;, ,&nbsp;Chenglong Yan,&nbsp;, ,&nbsp;Shanyou Yu,&nbsp;, ,&nbsp;Chunjing Yu*,&nbsp;, and ,&nbsp;Liping Chen*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c01019","DOIUrl":"10.1021/acs.molpharmaceut.5c01019","url":null,"abstract":"<p >Prostate-specific membrane antigen (PSMA) is a biomarker and molecular imaging target with the potential for the development and application of theranostic radiopharmaceuticals. Our study designed and developed PSMA-targeted small-molecule structures with diagnostic and therapeutic significance and screened out a precursor molecular structure NYM036 with PET diagnostic and fluorescence imaging potential and mainly explored the PET imaging biodistribution and fluorescence imaging of [⁶⁸Ga]Ga-NYM036 in prostate cancer model mice. After design and optimization, a small-molecule structure (named NYM036) characterized with fluorescence imaging and radionuclide-labeling functions was obtained. In the LNcaP prostate cancer mouse model, the preclinical targeted imaging efficacy and biodistribution of [⁶⁸Ga]Ga-NYM036 were studied using microPET/CT imaging. The feasibility of using the fluorescence imaging function of [⁶⁸Ga]Ga-NYM036 for tumor boundary differentiation and surgical navigation was verified through live fluorescence imaging and simulation of the surgical resection of prostate cancer. MicroPET/CT imaging in LNcaP tumor-bearing mice showed that [⁶⁸Ga]Ga-NYM036 had quite a low accumulation in nontarget organs (except for kidneys) and a high uptake in tumors. Blocked with 10-fold of the mass dose of NYM036, the radioactive uptake in tumors decreased significantly (%ID/g-mean, from 20.91 ± 3.11 to 4.12 ± 0.54, <i>P</i> &lt; 0.001), with the tumor-to-muscle ratio decreased from 16.85 ± 5.09 to 3.57 ± 0.66, but the radiouptakes in other organs had no obvious change. [⁶⁸Ga]Ga-NYM036 had a high and fast biodistribution in tumors, and the high target uptake lasted at least for 3 h after injection (%ID/g-mean value: 1 h, 22.05 ± 3.72; 3 h, 25.11 ± 4.87). The acute toxicity experiments conducted in ICR mice showed the good safety of [⁶⁸Ga]Ga-NYM036. Fluorescence imaging and tumor resection surgery with [⁶⁸Ga]Ga-NYM036 in LNcaP tumor-bearing mice displayed that the nuclide-labeled PSMA-targeting radiotracer [⁶⁸Ga]Ga-NYM036, which was coupled via a covalent bond with the Cy7 fluorescent dye, has a significant imaging effect and a good surgical navigation function for tumor tissues in the LNcaP prostate cancer mouse model. The PET imaging analysis results of radioactive uptakes for tumors and multiple organ tissues showed that [⁶⁸Ga]Ga-NYM036 has a good targeting capability for tumors, a low uptake in nontarget organs, and a good PET imaging efficiency in prostate cancer models. [⁶⁸Ga]Ga-NYM036 PET imaging may be applied to diagnosis and preoperative planning, and its fluorescence imaging function can be used in intraoperative navigation and postoperative efficacy evaluation, helping to achieve precise clearance surgery and subsequent treatment of prostate cancer.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 10","pages":"6290–6301"},"PeriodicalIF":4.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of the Antitumor Efficacy of Docetaxel Using αvβ3 Integrin and CD44 Dual Receptor-Targeted Carbon Dot-Based Nanodelivery in Breast Cancer","authors":"Pradip Jana,&nbsp;, ,&nbsp;Pratikshya Sa,&nbsp;, ,&nbsp;Kentaro Sakai,&nbsp;, ,&nbsp;Sanjeeb Kumar Sahoo,&nbsp;, ,&nbsp;Harishkumar Madhyastha,&nbsp;, and ,&nbsp;Abhimanyu Dev*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00823","DOIUrl":"10.1021/acs.molpharmaceut.5c00823","url":null,"abstract":"<p >Breast cancer is one of the most common forms of cancer, and an alternate treatment strategy for breast cancer is of utmost importance, as conventional therapy brings severe side effects. Here, we have developed a hyaluronic acid (HA) and cyclic arginine–glycine–aspartic acid peptide (cRGD)-conjugated docetaxel (DTX)-loaded nitrogen-doped carbon dot (CDU)-targeted delivery system for breast cancer. The developed dual-ligand-conjugated system (cRGD-HA-CDU@DTX) has exhibited a size below 100 nm, a high ζ potential (−24.3 mV), good biocompatibility, and good hydrophilicity. The cRGD-HA-CDU@DTX system has demonstrated a high drug loading efficiency (77.53%) and shown an acidic pH (pH 5.0)-dependent drug release of 90% after 48 h. According to the <i>in vitro</i> cytotoxicity study in the Michigan Cancer Foundation-7 (MCF-7) cancer cell line, the IC₅₀ value for the cRGD-HA-CDU@DTX system is found to be 3.167 μM, while for DTX, it is found to be 4.068 μM, indicating better cytotoxicity of the dual-ligand-conjugated system. Cellular uptake study exhibited the excellent internalization of the dual-ligand-conjugated system and a higher reactive oxygen species (ROS) production in cRGD-HA-CDU@DTX as compared to native DTX is seen. Flow cytometry analysis in MCF-7 cells demonstrated an almost 3-fold increased apoptotic cell death for the cRGD-HA-CDU@DTX group compared to DTX alone. Additionally, cell cycle analysis revealed 15% G₂/M arrest in the cRGD-HA-CDU@DTX-treated cells, whereas only 3.6% G₂/M arrest was noted for DTX. Further, the cRGD-HA-CDU@DTX system exhibited a significant upregulation and downregulation of proapoptotic and antiapoptotic genes, respectively. Finally, <i>in vivo</i> antitumor study displayed a 64.12% tumor growth reduction in the cRGD-HA-CDU@DTX-treated group, while DTX exhibited only a 39.98% tumor growth reduction. Thus, the overall study demonstrated that the cRGD-HA-CDU@DTX system can serve as a potential targeted nanodrug delivery system to reduce side effects and to improve therapeutic efficacy in breast cancer.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 10","pages":"6120–6140"},"PeriodicalIF":4.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Approaches to Diabetic Wound Healing: Focusing on ROS and Redox Signals","authors":"Akshita Jain,&nbsp;, ,&nbsp;Tejaswini Kolipaka,&nbsp;, ,&nbsp;Giriraj Pandey,&nbsp;, ,&nbsp;Abhipsa Priyadarshinee,&nbsp;, ,&nbsp;Niharika Puri,&nbsp;, ,&nbsp;Swapnil Shinde,&nbsp;, and ,&nbsp;Saurabh Srivastava*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00491","DOIUrl":"10.1021/acs.molpharmaceut.5c00491","url":null,"abstract":"<p >Reactive oxygen species (ROS) play a critical role in the pathophysiology of diabetic wound healing. In the early stages, a moderate increase in ROS levels is beneficial, as it enhances phagocytic activity and provides defense against external damage. However, as healing progresses, excessive ROS production induces oxidative stress, reduces antioxidant enzyme activity, and leads to redox imbalance─ultimately contributing to the development of chronic diabetic wounds. This review comprehensively explores the role of ROS across various phases of the wound-healing process and elucidates the associated signaling pathways. It also examines the influence of ROS on key mediators of wound healing, including macrophages and matrix metalloproteinases. To modulate ROS levels and promote efficient wound healing, we discuss a range of antioxidant-based therapeutic strategies, such as the application of biopolymers and antioxidant enzymes. Among the diverse antioxidant strategies, nanozymes stand out for their inherent ability to mimic the catalytic functions of natural enzymes. Owing to their unique ROS scavenging capabilities, they hold great promise in addressing the key challenges associated with anti-ROS therapy. Nanozymes provide several distinct advantages, including enhanced stability, multifunctionality, and tunable catalytic activity. Moreover, they play a crucial role in modulating the inflammatory responses induced by the pathological microenvironment. The article further highlights the potential of phytoconstituents in mitigating oxidative stress and restoring redox balance. Additionally, it addresses current treatment strategies for diabetic wound management, while also evaluating the clinical progress and challenges associated with their development.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 10","pages":"5738–5766"},"PeriodicalIF":4.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[68Ga]Ga-HM or [68Ga]Ga-PM: Which Is Superior for PET/CT Imaging of HMGB1-Positive Tumors?","authors":"Kunyao Wang,&nbsp;, ,&nbsp;Wenqi Zhao,&nbsp;, ,&nbsp;Xiaozhang Xu,&nbsp;, ,&nbsp;Ting Liang,&nbsp;, ,&nbsp;Chao Zhang,&nbsp;, ,&nbsp;Weijing Tao*,&nbsp;, ,&nbsp;Xin Li*,&nbsp;, and ,&nbsp;Feng Gao*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c01012","DOIUrl":"10.1021/acs.molpharmaceut.5c01012","url":null,"abstract":"<p >High mobility group box 1 (HMGB1) is highly expressed in various malignancies and has been considered as a promising molecular target for cancer diagnosis and therapy. In this study, two novel peptide-based radiotracers targeting HMGB1 were synthesized, each achieving high radiochemical purity (&gt;95%). Of these tracers, [⁶⁸Ga]Ga-HM possessed superior characteristics with a high binding affinity for the PC3 cell line (<i>K</i>_d = 46.11 ± 0.97 nM). Micro-PET imaging and biodistribution investigation in PC3 tumor-bearing mice revealed significant tumor uptake (SUV_max = 1.52 ± 0.10) and an excellent tumor-to-muscle ratio (6.96 ± 0.64) at 30 min post-injection. Moreover, robust imaging performance and favorable biodistribution profiles were consistently observed for [⁶⁸Ga]Ga-HM across multiple distinct HMGB1-positive tumor models. These findings demonstrate that [⁶⁸Ga]Ga-HM could serve as a diagnostic tracer to identify tumors with high HMGB1 expression, enabling personalized cancer treatment through the selection and monitoring of targeted therapeutic approaches.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 10","pages":"6279–6289"},"PeriodicalIF":4.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic Multinuclear Nickel-Polyphenol Artificial Enzyme with Synergistic Catalytic Centers for Broad-Spectrum RONS Scavenging: A Therapeutic Strategy against LPS-Induced Septic Cardiomyopathy","authors":"Yuying Wang,&nbsp;, ,&nbsp;Ruifang Li,&nbsp;, ,&nbsp;Longwu Xu,&nbsp;, ,&nbsp;Xiufeng Xu,&nbsp;, ,&nbsp;Shulan Pang,&nbsp;, ,&nbsp;Xiaotong Zhang,&nbsp;, ,&nbsp;Qiuhong Jiao,&nbsp;, ,&nbsp;Xiaoxin Lv,&nbsp;, ,&nbsp;Yulin Shen,&nbsp;, ,&nbsp;Yudan Zhao,&nbsp;, ,&nbsp;Xiaohong Liu,&nbsp;, ,&nbsp;Xinjun Yu*,&nbsp;, ,&nbsp;Baolong Zhou*,&nbsp;, and ,&nbsp;Tao Wang*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00644","DOIUrl":"10.1021/acs.molpharmaceut.5c00644","url":null,"abstract":"<p >Myocardial injury constitutes a life-threatening complication of sepsis, driven by synergistic oxidative-inflammatory pathology involving dysregulated production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and proinflammatory cytokines. This pathophysiological cascade remarkably elevates morbidity and mortality rates in septic patients, emerging as a key contributor to poor clinical outcomes. Despite its clinical significance, no clinically validated therapeutics currently exist for managing septic cardiomyopathy. Here, we present a novel nickel-salvianolic acid B metallopolymer (Ni-SalB) engineered through metal-coordination-driven self-assembly. This biohybrid therapeutic demonstrates multimodal catalytic efficacy in counteracting lipopolysaccharide (LPS)-induced myocardial injury through coordinated oxidative stress mitigation and inflammation regulation. The integration of catechol-carboxyl dual coordination centers with phenolic frameworks creates a synergistic system enhancing structural stability while enabling tandem catalytic cascade: (1) superoxide dismutase (SOD)-mimetic conversion of superoxide radicals (O₂^•–) to H₂O₂, followed by (2) glutathione peroxidase (GPx)-like decomposition of H₂O₂ to water. Mechanistic studies revealed the multifunctional scavenging capacity of Ni-SalB against diverse cytotoxic species, including hydroxyl radicals (^•OH) and reactive nitrogen species(RNS), through electron transfer and radical recombination pathways. In murine sepsis models, Ni-SalB administration markedly attenuated myocardial oxidative damage, while enhancing endogenous antioxidant defenses. Histopathological analysis demonstrated therapeutic preservation of myocardial architecture, showing not only a great reduction in inflammatory infiltration but also a remarkably decrease in collagen deposition compared to septic controls. The catechol-carboxyl coordination architecture conferred enhanced pharmacokinetic properties with prolonged circulation life, while maintaining favorable biosafety profiles. This study introduces a metallo-polymeric artificial enzyme strategy with dual catalytic antioxidant systems, presenting a paradigm-shifting approach for managing sepsis-induced cardiac complications and expanding the translational promise of redox-modulation therapies.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 10","pages":"5999–6013"},"PeriodicalIF":4.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voices in <i>Molecular Pharmaceutics</i>: Meet Dr. Wei Shao, Who Designs and Synthesizes Organic Functional Materials for Phototheranostics.","authors":"Wei Shao","doi":"10.1021/acs.molpharmaceut.5c01291","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c01291","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability Testing Reveals Photoselective Clipping of Heavy Chain C-Terminal Amino Acids That Leads to Fragmentation and Aggregation of an Antibody Fab Fragment","authors":"Arka Mukhopadhyay,&nbsp;, ,&nbsp;Kersti Karu,&nbsp;, and ,&nbsp;Paul A. Dalby*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00592","DOIUrl":"10.1021/acs.molpharmaceut.5c00592","url":null,"abstract":"<p >We built a custom device to subject an antibody fragment A33 Fab to controlled stress conditions that combined pH, temperature, agitation, and LED-based light exposure in polypropylene microplates; to simulate the real-world challenges it may encounter during storage and transportation and to evaluate the key degradation routes in Fab formulations. We also explored the addition of Tween 80 as a surfactant and the impact of plate surface siliconisation. Monomer loss and fragmentation was monitored by size-exclusion chromatography, aggregate formation determined by changes in hydrodynamic radius in DLS, and chemical modifications identified through intact mass analysis by LC-MS, and N-terminal sequencing. The findings indicated that the light exposure conditions often interacted with other factors. In particular, light exposure in the UV to blue range led to chemical degradations that led to greater susceptibility to aggregation, particularly at elevated temperatures. Interestingly, while Tween 80 provided stabilization, particularly within siliconized plates, the presence of Tween 80 also promoted losses due to light exposure, consistent with previous findings that Tween 80 could act as a photosensitizer. Exposure of A33 Fab to light led to sequential losses of amino acids selectively from only the heavy chain C-terminus, indicating a photosensitive hotspot in that region of the Fab structure. These also suggested that photoinduced clipping of the heavy chain C-terminus increased the susceptibility of A33 Fab to fragmentation into heavy and light chains and aggregation, consistent with previous work in which flexibility-suppressing mutations of the hinge region decreased the aggregation kinetics.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 10","pages":"5939–5951"},"PeriodicalIF":4.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00592","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Lipid Microbubble Targeting E-Selectin for Ultrasound Molecular Imaging of Acute Kidney Injury in Rats","authors":"Ruoyan Si,&nbsp;, ,&nbsp;Changan Zhao,&nbsp;, ,&nbsp;Liping Mo,&nbsp;, ,&nbsp;Zeyu Xu,&nbsp;, ,&nbsp;Yujin Zong,&nbsp;, ,&nbsp;Ziyan Jia,&nbsp;, ,&nbsp;Wenbao Zhao,&nbsp;, ,&nbsp;Jiamei Lu,&nbsp;, ,&nbsp;Xiaodong Xue,&nbsp;, ,&nbsp;Lina Chen*,&nbsp;, ,&nbsp;Rongguo Fu*,&nbsp;, and ,&nbsp;Shuting Ren*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00883","DOIUrl":"10.1021/acs.molpharmaceut.5c00883","url":null,"abstract":"<p >Acute kidney injury (AKI) is a common clinical syndrome characterized by abnormal renal function and structure. Microcirculatory perfusion disorders and inflammatory responses are critical pathophysiologies of AKI. Recently, ultrasound molecular imaging has been considered a valuable tool for preclinical and clinical diagnostics that can sensitively target histological structures of interest, particularly in evaluating renal microcirculation. The purpose of this study was to explore a lipid microbubble (MB_E-selectin) that targets E-selectin molecules expressed on the activated endothelium and to perform ultrasound molecular imaging for the kidney in cisplatin-induced AKI in rats. Using freeze-drying methods, three formular nontargeted microbubbles (NMBs-1, NMBs-2, NMBs-3) were prepared, and three corresponding MB_E-selectin suspensions (MB_E-selectin-1, MB_E-selectin-2, MB_E-selectin-3) were constructed via maleimide–thiol conjugation chemistry. The results revealed that the physicochemical characteristics of three NMBs and MB_E-selectin suspensions were usable for intravenous injection as ultrasound contrast agents (UCAs), and the anti-E-selectin antibody successfully conjugated to the lipid shell surface of the bubbles in three MB_E-selectin suspensions, which could bind specifically to E-selectin molecules expressed on human umbilical vein endothelial cells (HUVECs) treated with tumor necrosis factor-alpha (TNF-α). During ultrasound imaging for the kidney in the cisplatin-induced AKI model, the time-to-peak (TTP) and area under the curve (AUC) of the MB_E-selectin-2 suspension significantly increased, but the wash-in rate (WIR) and wash-out rate (WOR) significantly decreased compared with those of the NMBs-2 suspension or the control group. The normalized differential targeted enhancement (NdTE) of the MB_E-selectin-2 suspension was significantly greater than that of the NMBs-2 suspension in the model group, as was the residual-to-saturation ratio (RSR) at 8 min. In conclusion, we successfully prepared a novel MB_E-selectin suspension carrying an anti-E-selectin antibody that can be used for intravenous injection and can enhance ultrasound imaging of the kidney as a UCA, particularly in a cisplatin-induced AKI model. Ultrasound molecular imaging of the MB_E-selectin suspension may be helpful for evaluating renal microcirculation or injury in AKI diseases.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 10","pages":"6163–6173"},"PeriodicalIF":4.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bile Acid-based Microcapsule-Like Cocrystals of Phytosterols with Enhanced Solubility, Bioavailability, and Bioactivity.","authors":"Lei Tang, Yinan Feng, Yifei Bian, Zhixiong Sun, Qiaoce Ding, Dongying Chen, Jian-Rong Wang, Xuefeng Mei","doi":"10.1021/acs.molpharmaceut.5c00851","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00851","url":null,"abstract":"<p><p>Phytosterols are a class of natural steroids found in various plants. Commercially available phytosterols (PS) are primarily extracted from the deodorized distillate of soybean oil and consist predominantly of β-sitosterol with smaller amounts of stigmasterol and campesterol. Numerous studies have consistently demonstrated the significant lipid-lowering activity of PS. However, the application of PS is limited due to their low oral bioavailability. To enhance the water solubility and in turn the absorption of PS at the molecular level, microcapsule-like cocrystals were designed using bile acids via hydrogen bonding. As expected, four microcapsule-like cocrystals were successfully prepared: β-sitosterol with cholic acid (CA) and chenodeoxycholic acid (CDCA), and PS with CA and CDCA. The cocrystal of PS with CA (PS-CA) was selected for further investigation, and the results demonstrated that PS-CA exhibited significantly enhanced solubility <i>in vitro</i> and markedly improved oral bioavailability <i>in vivo</i>. Specifically, the AUC_1-24 h of PS-CA was 6 times that of PS, while the <i>C</i>_max was 4 times. Moreover, as a result of the improved bioavailability of PS, PS-CA showed superior lipid-lowering activity.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}