Molecular Pharmaceutics最新文献

{"title":"","authors":"Qing Zhou, Hailong Ma, Hongling Xu, Yuyang Bai, Chang Tan, Yangxue Su, Yang Li*, Xue Ying* and Yaxin Zheng*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144357915","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":"","authors":"Katarzyna Solarska-Ściuk*,  and , Hanna Pruchnik, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00501","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144357916","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":"","authors":"Sixuan Cheng, Youzhuo Quan, Xingru Long, Xiaoli Lan, Dawei Jiang*, Kun Liu* and Cheng Fan*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144357918","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":"","authors":"Madison M. Davis, Irnela Bajrovic and Maria A. Croyle*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.4c01186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144357920","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":"","authors":"Zhijun Li, Tukang Peng, Min Yang, Yifan Qiu, Peizhen Ye, Xiaohui Wang* and Hongjun Jin*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144353546","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":"CD7-Targeted Cytotoxic Potency of Diphtheria Toxin- and Ricin-Based Immunotoxins in Targeted Therapy for T-Cell Acute Lymphoblastic Leukemia.","authors":"Hyun Bin Lee, Seong Guk Park, Hyo Jeong Kim, Jun Pyo Jeon, SuHyeon Oh, SangJoon Lee, Sung Ho Park, Sebyung Kang","doi":"10.1021/acs.molpharmaceut.5c00146","DOIUrl":"10.1021/acs.molpharmaceut.5c00146","url":null,"abstract":"<p><p>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and heterogeneous hematologic malignancy, underscoring the urgent need for innovative treatments such as immunotoxins, which combine specific antigen targeting with potent cytotoxic activity. In this study, we developed two distinct immunotoxins (aCD7Nb/DTA and RTA/aCD7Nb) by combining the CD7-binding nanobody (aCD7Nb) with recombinant diphtheria toxin (DTA) and ricin (RTA), utilizing SpyCatcher/SpyTag (SC/ST) post translational protein ligation system for targeted therapy in T-cell acute lymphoblastic leukemia (T-ALL). Both aCD7Nb/DTA and RTA/aCD7Nb specifically bind to three CD7-expressing T-ALL cell lines, CCRF-CEM, Jurkat, and MOLT-4 cells, based on CD7 expression levels, but not to the CD7-negative Raji B-ALL cells. Both aCD7Nb/DTA and RTA/aCD7Nb demonstrated high cytotoxic against T-ALL cells, with IC₅₀ values inversely correlated to CD7 expression. Notably, RTA/aCD7Nb exhibited approximately 2-fold higher anticancer efficacy compared to aCD7Nb/DTA in both CCRF-CEM and Jurkat cells. In an orthotopic model of CCRF-CEM T-ALL-engrafted NSG mice, systemic administration of RTA/aCD7Nb effectively inhibited T-ALL progression and extended survival, without any adverse effects. These findings underscore the potential of combining a CD7-binding ligand with an appropriate active toxin moiety to significantly enhance the efficacy of immunotoxins against T-ALL.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"3255-3267"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951297","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":"Purpurin/Indocyanine Green Nanocomposite for Restricting Glutaminolysis to Enhance Dual Phototherapy of Cancer.","authors":"Sen Li, Shenyi Wang, Yanfei Cai, Dong Hua, Jian Jin, Hao Zhang, Zhaoqi Yang","doi":"10.1021/acs.molpharmaceut.5c00001","DOIUrl":"10.1021/acs.molpharmaceut.5c00001","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising noninvasive cancer treatments owing to their precision and convenience. Indocyanine green (ICG), a dual-functional agent capable of generating both PDT and PTT effects under single-wavelength laser irradiation, is widely explored in oncology. However, ICG faces limitations such as poor bioavailability, rapid systemic clearance, and tumor microenvironment glutathione (GSH) overexpression, which scavenges reactive oxygen species (ROS) and diminishes therapeutic efficacy. To address this, we developed albumin-based nanoparticles (ICG&purpurin@BSA) co-encapsulating ICG and purpurin. Purpurin inhibits mitochondrial glutaminolysis, a metabolic pathway critical for GSH synthesis, thereby reducing GSH-mediated ROS depletion. Flow cytometry and Western blot analyses confirmed significant GSH downregulation. The nanocomposite demonstrated robust anticancer effects in vitro and in vivo, achieving near 90% tumor growth suppression within 12 days. The outcomes of this research demonstrate the benefits of combining biocompatible nanocomposites with glutamine pathway inhibitors and dual phototherapy agent ICG.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"3073-3083"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951453","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":"Cytidinyl/Cationic Lipid Encapsulating Insulin-Like Growth Factor 1 Receptor siRNA for Hepatocellular Carcinoma Therapy.","authors":"Yang Pu, Quanxin Wang, Yufei Pan, Xixian Wang, Zhu Guan, Yuejie Zhu, Zhenjun Yang","doi":"10.1021/acs.molpharmaceut.4c01318","DOIUrl":"10.1021/acs.molpharmaceut.4c01318","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most prevalent form of invasive liver cancer, representing over 90% of all liver cancer cases. Currently, there is a lack of targeted therapy for HCC. Insulin-like growth factor 1 receptor (IGF1R) is abnormally expressed in HCC, leading to the malignant proliferation and contributing to the antiapoptosis mechanisms in tumor cells. In this study, small interfering RNAs targeting IGF1R mRNA (siIGF1Rs) have been designed. Additionally, a full 2'-F/2'-OMe modification with partial phosphorothioation was applied to improve the biological properties of these siIGF1Rs. Based on previous research, stable lipid complexes with uniform particle sizes were constructed using cytidinyl lipid DNCA/cationic lipid CLD (Mix) supplemented with DSPE-PEG (siIGF1R/Mix/PEG). The complexes were formed through hydrogen-bonding, π-π stacking, and electrostatic interactions. The siIGF1R/Mix/PEG complex entered the cytoplasm and nucleus of HCC cells, reduced IGF1R mRNA and pre-mRNA levels by over 95% and 50% respectively, further arrested the cell cycle in the S phase, and promoted cell apoptosis. Importantly, siIGF1R/Mix/PEG (0.8 mg/kg, i.v.) selectively accumulated in the tumor, significantly inhibiting tumor growth by 91.31% compared to the naked siRNA group, with slower release and a more prolonged effect.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2939-2951"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951583","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":"Design of Coamorphous Systems for Flavonoid Components Coformed with Meglumine by Integrating Theory-Model-Experiment Techniques.","authors":"Jiawei Han, Wen Sun, Jiaxin Chen, Zhimin Yue, Weitao Fang, Xiaoqian Liu, Jue Wang, Gaorong Wu","doi":"10.1021/acs.molpharmaceut.4c01536","DOIUrl":"10.1021/acs.molpharmaceut.4c01536","url":null,"abstract":"<p><p>Flavonoids represent an extensive group of phenolic substances in vegetables, fruits, grains, tea, flowers, etc., which show a variety of biological activities in various nutraceutical, cosmetic, and medicinal fields. Despite demonstrating multifunctional bioactive properties relevant to nutraceutical and pharmaceutical applications, their clinical utilization faces challenges due to their generally low water solubility. This study established a systematic methodology combining computational modeling and experimental validation for developing flavonoid-meglumine (MEG) coamorphous formulations. The initial screening identified 13 flavonoid compounds exhibiting favorable miscibility with MEG from 15 candidates through Hansen solubility parameter analysis. Subsequent molecular dynamics simulations revealed potential hydrogen bond formation in six selected flavonoids (BAI, HES, NAR, KAE, QUE, and ISO) with MEG. Then, six flavonoid coamorphous systems were successfully prepared via the melt-quenching method and characterized by PLM, PXRD, and differential scanning calorimetry. FTIR and radial distribution function analysis results collectively confirmed intermolecular hydrogen bond interactions within these binary systems. In vitro dissolution studies revealed significant solubility/dissolution enhancement in both pH 1.2 HCl and pH 6.8 phosphate buffers, maintaining long-term supersaturation for all six coamorphous formulations. Meanwhile, six flavonoid coamorphous systems had superior stability over individual flavonoid amorphous components, which were attributed to the stronger intermolecular interactions by higher binding energy calculation. These results indicated that the obtained flavonoid coamorphous systems performed a promising application potential in functional products. Importantly, this study presents a novel design framework integrating computational prediction, molecular modeling, and experimental validation for systematic screening of flavonoid coamorphous formulations.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"3045-3060"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952822","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":"3D Printed Hollow Microneedles for Dermal and Transdermal Drug Delivery: Design, Fabrication, Application, and Perspective.","authors":"Amirreza Ghaznavi, Sonia Alavi, Yang Lin, Seth A Hara, Richard A Gemeinhart, Jie Xu","doi":"10.1021/acs.molpharmaceut.4c01261","DOIUrl":"10.1021/acs.molpharmaceut.4c01261","url":null,"abstract":"<p><p>Hollow microneedles (HMNs) offer a transformative solution for topical diagnosis and therapeutic applications due to the unique challenges addressed by their ability to adjust dosing and their integration capabilities in the context of microfluidic and microelectronic devices. To fabricate HMN devices, 3D printing has been introduced as an advanced manufacturing technology in fabricating high-resolution micro- and nanofeatures overcoming the inferior capabilities of traditional manufacturing technologies such as lithography, etching, and laser fabrication in producing sophisticated devices. In this paper, a comprehensive review of recent advancements in the utilization of 3D printing technology for developing HMN devices is provided. The current fabrication technologies are summarized. In addition, design, fabrication, and testing considerations for generating HMN devices are summarized. Various applications, including drug delivery, sensing, and recording, along with integrated devices necessary for these applications are highlighted. Finally, the limitations of the current approaches are discussed, and the future of HMN devices fabricated by the 3D printing technology is proposed. In summary, this Review provides insight into the current status of 3D printed HMN devices and a roadmap for developing HMNs including design criteria, fabrication considerations, postprocessing approaches, and required testing for device functionality evaluation.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2747-2764"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955320","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}