Molecular Pharmaceutics最新文献

{"title":"Inflammation-Targeted Molecular Imaging for Myocarditis: Recent Advances in Target Mechanisms, Probe Development, and Translational Applications","authors":"Zhou Ye,&nbsp;Linlin Fu,&nbsp;Xi Ye,&nbsp;Xin Lu,&nbsp;Fan Zhang,&nbsp;Yingqi Ran,&nbsp;Manman Zhu*,&nbsp;Duo Xu* and Lan Yao*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00450","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00450","url":null,"abstract":"<p >Inflammation is the key feature of myocarditis, which remains challenging to diagnose due to its complex etiology and nonspecific clinical presentation. In recent years, inflammation-targeted molecular imaging has become a research priority, and noninvasive monitoring of cardiac inflammation is expected to improve the accuracy of clinical diagnosis. This review focuses on the molecular imaging probes and targets for myocarditis in radionuclide imaging, ultrasound imaging, and magnetic resonance imaging (MRI), discussing the characteristics and applications of each probe-target combination and their potential limitations. Molecular targeted imaging approaches for inflammatory cell phenotypes, metabolic pathways, and endothelial cell markers hold significant potential for clinical translation and allow for early detection and treatment monitoring of myocarditis, thereby enabling better patient care and improving clinical outcomes.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5244–5256"},"PeriodicalIF":4.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921018","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":"Principle and Application of Novel Negative Air (Oxygen) Ion Storage and Release Products","authors":"Angze Li,&nbsp;Jun Wang,&nbsp;Wei Zhu,&nbsp;Muqing Liu* and Shangfeng Liu*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00361","DOIUrl":"10.1021/acs.molpharmaceut.5c00361","url":null,"abstract":"<p >Negative air ions (NAI) are ions present in the air that enhance blood oxygen absorption and utilization, stimulate metabolism, and modulate mood and nervous system activity. However, the application of NAI has been limited by storage challenges and low concentrations due to the conditions under which they are produced and the nature of the ions themselves. In order to overcome these limitations and develop NAI as a viable method of treatment, we have introduced a novel, highly concentrated NAI prodrug that incorporates NAI into flaxseed oil. This innovative drug can be administered in liquid, semiliquid, and dietary forms. Additionally, we have explored various NAI-related actions and mechanisms, such as the antiaging effects of these drugs through ROS inhibition. Our research has shown that NAI agents can penetrate the brain through the skin and the blood–brain barrier, rapidly reoxygenating cells throughout the body. Particularly, NAI has demonstrated excellent antitumor and cognitive-enhancing properties. These findings have significant implications for the potential of our NAI-based prodrug as a groundbreaking approach in antiaging therapy, providing a novel strategy for enhancing endogenous oxygenation and treating respiratory compromise and beyond.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5400–5409"},"PeriodicalIF":4.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881713","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":"Multiscale Diffusion, Dynamic Cluster Formation, and Intermolecular Interactions in Pharmaceutically Relevant Monoclonal Antibody Formulations","authors":"Ilaria Mosca*,&nbsp;Christian Beck,&nbsp;Laura Mateo-Miñarro,&nbsp;Roody Nasro,&nbsp;Anna Carlotta Grundel,&nbsp;Ingo Hoffmann,&nbsp;Kévin Pounot,&nbsp;Olga Matsarskaia,&nbsp;Christoph Grapentin,&nbsp;Tilo Seydel* and Frank Schreiber*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00327","DOIUrl":"10.1021/acs.molpharmaceut.5c00327","url":null,"abstract":"<p >Due to their specificity and versatility, monoclonal antibodies (mAbs) are the most popular class of biopharmaceuticals typically administered via intravenous injection. One of the current pharmaceutical challenges concerns mAb formulations for subcutaneous (SC) injection, which is gaining importance as an alternative administration route offering convenience to patients by allowing self-administration compared to other parenteral delivery methods. With volumes lower than 1–2 mL being better tolerated in the subcutaneous space, highly concentrated mAb formulations are needed to achieve significant therapeutic effects, potentially increasing the solution viscosity and altering drug injectability. The main challenge is to maintain the solution viscosity below the SC injectability threshold (15–20 mPa·s) while preserving solution stability. Since the understanding of macroscopic viscosity requires in-depth knowledge on protein multiscale diffusion, mutual interactions, and aggregation, we employ two complementary neutron scattering techniques to investigate 9 different mAbs of IgG1/IgG4 subtypes in aqueous solution as a function of protein concentration and temperature. The synergy between neutron spin-echo (NSE), a spectroscopy technique providing dynamic information, and small-angle neutron scattering (SANS), a time-averaged static technique, enables us to probe the short-time collective diffusion of different mAbs, explore their self-association into small transient clusters, their intermolecular interactions, and ultimately access their internal dynamics. This study builds on previous neutron backscattering (NBS) findings, bridging a critical gap between the time scales probed by NBS and viscometry. It also confirms that the formation of short-lived clusters comprising more than two monomers is a key factor driving high solution viscosity, phase separation, and opalescence.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5373–5388"},"PeriodicalIF":4.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870359","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. Kenneth Waterman, Who Brings Drugs to Patients Faster.","authors":"Kenneth C Waterman","doi":"10.1021/acs.molpharmaceut.5c01169","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c01169","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870360","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":"The Impact of Dosimetry Extrapolation Methods for Theranostic Applications of Fibrosing Mediastinitis","authors":"Liwei Song,&nbsp;Xufu Chen,&nbsp;Xiang Li,&nbsp;Zongtai Han,&nbsp;Shu Zhang,&nbsp;Meiling Zhang,&nbsp;Liyun Zhang,&nbsp;Lizhen Lan,&nbsp;Sijin Li,&nbsp;Jianbo Cao,&nbsp;Marcus Hacker,&nbsp;Yiwei Shi*,&nbsp;Jianguo Li* and Zhifang Wu*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00635","DOIUrl":"10.1021/acs.molpharmaceut.5c00635","url":null,"abstract":"<p >Fibrosing mediastinitis (FM) is a benign but potentially fatal condition characterized by excessive fibrous tissue proliferation in the mediastinum, leading to compression of vital structures. A radioisotope-based therapeutic approach using ¹⁷⁷Lu-FAPI-46 has demonstrated promising results in preclinical models; however, the lack of animal-to-human dosimetry data has hindered clinical translation. In this study, we aimed to evaluate various animal-to-human dosimetry extrapolation methods to support the potential clinical use of ¹⁷⁷Lu-FAPI-46 in FM treatment. Five extrapolation methods were investigated, including direct application of rat time-integrated activity coefficients (TIACs) to human organs (M1), relative mass scaling (M2), metabolic rate scaling (M3), combined mass and metabolic rate scaling (M4), and organ-specific allometric scaling (M5). The correlation between these methods and uterine uptake, as well as clinical imaging data, was further analyzed. Notable variability was observed in the estimated absorbed dose distribution across organs using the different methods, with higher uptake consistently noted in the intestines, kidneys, ovaries, and uterus. Physiological uptake in the uterus, ovaries, and small intestine was confirmed, and the uterus was identified as the dose-limiting organ, with the maximum permissible administered activity estimated to be below 2.78 GBq. Extrapolated absorbed dose estimates suggest that a uterine dose of 16 Gy could be reached with an administered activity of less than 2.78 GBq, depending on the dosimetry model used. These findings highlight the necessity of careful dose planning and special consideration for protecting reproductive organs, particularly in younger female patients, during future clinical trials of ¹⁷⁷Lu-FAPI-46 for FM.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5616–5626"},"PeriodicalIF":4.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858700","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":"Mitochondrially Targeted p53-Bad* Fusion Gene Therapy Promotes Apoptosis in Hepatocellular Carcinoma by Pan-Bcl-2 Inhibition","authors":"Braxten D. Hornsby,&nbsp;Julius K. K. Tuekpe,&nbsp;Cassidy A. Steele,&nbsp;Amber A. Devereaux,&nbsp;Katherine E. Redd Bowman* and Carol S. Lim*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00773","DOIUrl":"10.1021/acs.molpharmaceut.5c00773","url":null,"abstract":"<p >Presenting a considerable disease burden and global health threat, hepatocellular carcinoma (HCC) is in desperate need of potent and effective therapies. p53-Bad* is designed to provide mitochondrial targeting, enhance binding interactions with antiapoptotic Bcl-2 family members, and improve apoptotic activity in various cancers. While we have shown that fusion of p53 and Bad* improves mitochondrial localization and increases apoptosis in HCC, critically, the mechanism of action and nature of this heightened apoptotic function have not been delineated. Here, the functional activity and apoptotic mechanism of action of our p53-Bad* construct was explored, demonstrating that fusion of pro-apoptotic Bad* to p53 does indeed enhance interactions with antiapoptotic Bcl-2 family members Mcl-1, Bcl-2, and Bcl-xL relative to p53-WT. We confirm that p53-Bad* acts as a pro-apoptotic agent specifically at the mitochondria by inhibition and blockade of downstream Bak/Bax oligomerization events, rescuing cells from p53-Bad*-induced cytotoxicity and apoptosis. Using mutant p53-Bad* variants designed to disrupt binding interactions with antiapoptotic targets, a direct relationship between functional binding interactions and the apoptotic activity of p53-Bad* is established. These findings present strong evidence for the use of p53-Bad* as a pan-Bcl-2 inhibitor and synergistic pro-apoptotic agent in cancers with upregulation of multiple antiapoptotic and prognostic markers.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5652–5668"},"PeriodicalIF":4.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854008","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":"Organic Salts Based on Streptomycin: A New Approach for an Old Drug","authors":"Francisco Faísca,&nbsp;Andreia F. M. Santos,&nbsp;Mariana Ferreira,&nbsp;Paula Gameiro,&nbsp;Sofia A. C. Lima and Luis C. Branco*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00310","DOIUrl":"10.1021/acs.molpharmaceut.5c00310","url":null,"abstract":"<p >The growing threat of bacterial resistance is expected to become a leading cause of global mortality in the coming decades. Currently, the pharmaceutical industry is focused on the discovery of new efficient antibiotics as well as the reintroduction of discontinued drugs under the hypothesis that resistance to them may have declined. Another strategy is to use enhancers or adjuvants to counteract the current resistance mechanisms. In this study, both approaches are explored by employing an out-of-market antibiotic, streptomycin, combined with biocompatible sulfonate and carboxylate anions. Eight organic salts were synthesized via direct protonation, yielding stable solids at room temperature, and characterized in terms of their physicochemical properties, such as solubility, permeability, and thermal stability. Their biological properties were also investigated, including toxicity against human keratinocytes and antimicrobial activity against both susceptible and multidrug-resistant strains of <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, <i>Klebsiella pneumoniae</i>, <i>Staphylococcus aureus</i>, and <i>Staphylococcus epidermidis</i>. Among the synthesized compounds, one is an ionic liquid ([STPH₃][GluCOO]₃), while those with <i>p</i>-toluenesulfonate ([STPH₃][<i>p</i>-TolSO₃]₃), propanesulfonate ([STPH₃][C₃SO₃]₃), and glycolic acid ([STPH₃][GlyCOO]₃) showed the greatest potential for transdermal delivery due to their favorable combination of physicochemical and biological properties. [STPH₃][<i>p</i>-TolSO₃]₃ exhibited enhanced permeation in phospholipid bilayer assays along with promising biocompatibility and antimicrobial efficacy, making it a strong candidate for further investigation.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5361–5372"},"PeriodicalIF":4.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853922","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":"Correction to “Targeted Delivery of AR-V7 siRNA with Bivalent PSMA Aptamers Effectively Suppresses the Growth of Enzalutamide-Resistant Prostate Cancer”","authors":"Lu Xue,&nbsp;Xiaolin Yu,&nbsp;Lijing Zhao,&nbsp;Aria Garrett,&nbsp;Daqing Wu and Hong Yan Liu*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c01102","DOIUrl":"10.1021/acs.molpharmaceut.5c01102","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5710–5711"},"PeriodicalIF":4.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833489","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":"Hypoxia-Responsive Nano-Photosensitizer Anchored by PEGylated BODIPY: A Single-Laser-Driven Platform for Photo-Enhanced Synergistic Chemo/Photodynamic/Photothermal Cancer Therapy","authors":"De-Chao Yang,&nbsp;Huamei Zhuang,&nbsp;Jiayi Zheng,&nbsp;Liyang Du*,&nbsp;Jianmin Chen* and Jian-Yong Liu*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00646","DOIUrl":"10.1021/acs.molpharmaceut.5c00646","url":null,"abstract":"<p >The integration of chemotherapeutic drugs and photosensitizers into nanocarriers holds great potential for combining chemotherapy and phototherapy while reducing systemic toxicity. However, therapeutic efficacy is hindered by the hypoxic tumor microenvironment and the insufficient drug release. This study designs a multifunctional nano-photosensitizer BAP by conjugating hydrophobic boron dipyrromethene (BODIPY) with hydrophilic poly(ethylene glycol) via hypoxia-responsive azobenzene linkers. In aqueous media, BAP demonstrates self-assembly into stable nanoparticles (termed BAP NPs) that exhibit dual phototherapeutic functionalities. BAP NPs can be activated by single wavelength laser irradiation to initiate both photodynamic therapy (PDT) and photothermal therapy (PTT). The engineered BAP NPs further integrate dual-mode imaging capabilities, enabling fluorescence and photothermal imaging for nanocarrier visualization. To enhance antitumor efficacy, the chemotherapy doxorubicin (DOX) was further loaded into BAP NPs, forming nanomedicine BAP-DOX NPs. As expected, the azobenzene linkers of BAP are sensitive to the overexpressed azoreductase in hypoxic cancer cells, facilitating BAP disassembly and DOX release. Upon laser irradiation, the BAP component in BAP-DOX NPs eradicates superficial oxygen-rich tumor cells through PDT and PTT. PDT-caused oxygen consumption triggers acute hypoxia, enhancing DOX release in hypoxic tumor cells. Both in vitro and in vivo studies have demonstrated that BAP-DOX NPs exhibit remarkable antitumor activity through synergistic light-driven PDT/PTT and hypoxia-responsive chemotherapy. This research establishes an innovative therapeutic strategy to overcome hypoxia-induced therapeutic resistance through a simple photosensitizer-based nanocarrier that enables photo-enhanced drug release and synergistic chemo/photodynamic/photothermal tumor ablation.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5603–5615"},"PeriodicalIF":4.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833490","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":"Charged Particle Dynamics in Dry Powder Inhalers","authors":"Connor Williamson,&nbsp;Joshua Baptiste,&nbsp;Melanie Hamilton,&nbsp;Cheng Pang,&nbsp;David Prime,&nbsp;Anthony J. Stace and Elena Besley*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00485","DOIUrl":"10.1021/acs.molpharmaceut.5c00485","url":null,"abstract":"<p >Mechanisms for the growth of particles in a stream of aerosolised inhalation powders have been investigated computationally using experimentally measured stream compositions. Many-body electrostatic theory has been incorporated into classical particle dynamics simulations to describe the aggregation of charged, fine powder particles in the single and dual stream geometry of an inhaler. The simulations use experimental bipolar charge measurements recorded using a Dekati BOLAR as input. Evidence of a subtle relationship between charge and the dynamics of particle growth contributes to our understanding of the electrostatics and many-body interactions in inhalation powders. It is found that certain combinations of particle size and charge result in a scavenging process whereby small particles, which may be therapeutic, aggregate with large particles to become ineffective due to an overall increase in size. This process may have important implications for design of dry powder inhaler devices.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5485–5492"},"PeriodicalIF":4.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00485","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833425","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}