Molecular Pharmaceutics最新文献

{"title":"Probing the Effect of Fluorine on Hydrogen Bonding Interactions in a Pharmaceutical Hydrate Using Advanced Solid-State NMR.","authors":"Chaithanya Hareendran, T G Ajithkumar","doi":"10.1021/acs.molpharmaceut.4c01055","DOIUrl":"10.1021/acs.molpharmaceut.4c01055","url":null,"abstract":"<p><p>Structural studies of pharmaceutical hydrates are essential to understanding stability-related issues, especially during the heating process of formulation. A thorough understanding of the hydration and dehydration behavior of active pharmaceutical ingredient (API) hydrate is also important since phase transitions can occur during the formulation process. This is because dehydration could result in a considerable rearrangement in the structure if water-API hydrogen bonding is present. We perform advanced solid-state NMR experiments on regorafenib monohydrate to investigate the role of fluorine in hydrogen bonding interaction, and the results are compared to its anhydrous form and its structural analogue, namely, sorafenib. Our results show that significant structural changes could not be observed on dehydration. Based on our study, it can be concluded that the introduction of fluorine restricts the intramolecular hydrogen bonding and the asymmetry in the structure of regorafenib monohydrate is absent, in comparison to sorafenib.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1869-1880"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565511","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":"Docetaxel-Loaded Electrospun Nanofibrous Mats for Local Chemotherapy Targeting Positive Surgical Margins in Prostate Cancer.","authors":"Xing Li, Kun Yuan, Yisheng Yin, Yiqun Tian, Zihao Guo, Zhenliang Qin, Xiaoyong Zeng","doi":"10.1021/acs.molpharmaceut.4c01440","DOIUrl":"10.1021/acs.molpharmaceut.4c01440","url":null,"abstract":"<p><p>Positive surgical margins following radical prostatectomy significantly contribute to tumor recurrence. While systemic chemotherapy demonstrates limited efficacy in this context, local chemotherapy drug delivery systems based on nanomaterials offer promising strategies to address this issue by modifying drug release kinetics and distribution, thereby enhancing antitumor effects while minimizing the toxicities associated with systemic chemotherapy. In this study, we utilized electrospun nanofibrous mats loaded with docetaxel for sustained drug delivery. In vitro experiments demonstrated that these implantable drug-loaded nanofibrous mats effectively inhibited prostate cancer cell growth, induced cell cycle arrest, and promoted apoptosis. In animal models, these drug-loaded nanofibrous mats exhibited prominent therapeutic effects on positive surgical margins postoperatively. Importantly, docetaxel-loaded nanofibrous mats modulated the tumor immune microenvironment by suppressing M2-like macrophages, increasing the ratio between M1- and M2-like macrophages, and enhancing CD8+ T-cell infiltration. Local administration significantly reduced systemic toxicity compared to systemic chemotherapy. In summary, we developed an implantable electrospun drug-loaded nanofibrous mat for localized docetaxel delivery, which offers a prospective strategy for managing positive surgical margins after surgery.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2213-2223"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612842","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":"Enhanced Retention of NTSR1-Targeted Radionuclide Therapeutics via Covalent Inhibitors in Pancreatic, Colorectal, and Prostate Cancer Models.","authors":"Wenting Zhang, Wei Fan, Katie Brake, Alireza Basiri, Megan A Hyun, Lynette M Smith, Subodh M Lele, Abhijit Aithal, Maneesh Jain, Jered C Garrison","doi":"10.1021/acs.molpharmaceut.4c01324","DOIUrl":"10.1021/acs.molpharmaceut.4c01324","url":null,"abstract":"<p><p>Neurotensin receptor subtype 1 (NTSR1) is overexpressed in numerous cancers. Our laboratory is exploring the utilization of covalent cysteine protease inhibitors (e.g., E-64) to increase tumor retention of targeted radionuclide therapeutics (TRTs) through protein adduct formation. Using this approach, we reported [¹⁷⁷Lu]Lu-NA-ET1, an NTSR1-targeted construct. In this work, we continue the exploration of [¹⁷⁷Lu]Lu-NA-ET1 in three different NTSR1-positive cancer models. [¹⁷⁷Lu]Lu-3BP-227, a clinically investigated NTSR1-targeted construct, was utilized as a comparative benchmark. Both [¹⁷⁷Lu]Lu-NA-ET1 and [¹⁷⁷Lu]Lu-3BP-227 underwent in vitro investigation, including internalization and autoradiographic sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) studies, in NTSR1-positive AsPC-1, HT-29, and PC-3 cell lines. Biodistribution, human radiation dosimetry, and in vivo autoradiographic SDS-PAGE studies were performed by using the same models. A dose escalation study using 585 MBq (15.8 mCi) of [¹⁷⁷Lu]Lu-NA-ET1 was implemented in immunocompetent CF-1 mice. In all three cell lines, [¹⁷⁷Lu]Lu-NA-ET1 demonstrated similar cellular uptake profiles relative to those of [¹⁷⁷Lu]Lu-3BP-227. Biodistribution studies of [¹⁷⁷Lu]Lu-NA-ET1 revealed increased (1.9-4.4-fold) tumor retention and radiation dose delivery relative to the control. Analysis of the in vitro and in vivo cellular and tissue lysates showed protein adducts that ranged from approximately 25-35 kDa, consistent with cysteine cathepsins, the speculative protein binding partner. A total of 585 MBq (15.8 mCi) of [¹⁷⁷Lu]Lu-NA-ET1 was administered and found to be well-tolerated. Incorporating the covalent inhibitor in [¹⁷⁷Lu]Lu-NA-ET1 resulted in an improved retention and radiation dose delivery profile compared to [¹⁷⁷Lu]Lu-3BP-227. Examination of the therapeutic potential of [¹⁷⁷Lu]Lu-NA-ET1 and further exploration of the chemical biology of this approach is underway.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2131-2141"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655519","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":"Lyophilization Strategy Enhances the Thermostability and Field-Based Stability of Conjugated and Comixed Subunit Liposomal Adjuvant-containing Tuberculosis Vaccine Formulation (ID93 + GLA-LSQ).","authors":"Babatunde Ayodeji Adeagbo, Morayo Alao, Ochuko Orherhe, Abdulafeez Akinloye, Gerhardt Boukes, Elize Willenburg, Caryn Fenner, Oluseye Oladotun Bolaji, Christopher B Fox","doi":"10.1021/acs.molpharmaceut.5c00150","DOIUrl":"10.1021/acs.molpharmaceut.5c00150","url":null,"abstract":"<p><p>ID93 + GLA-LSQ is an adjuvanted recombinant protein vaccine candidate that has demonstrated robust T-cell immunity and reduced bacterial burden in preclinical studies. Here, we explored the strategy of lyophilization by introducing 10% Trehalose as a bulking agent and cryoprotectant to develop a thermostable single-vial formulation of ID93 + GLA-LSQ. We further examined the stability of lyophilized formulations stored at 4 and 37 °C in the research laboratory and field stability across five study sites. Co-mixed (CoVL) and conjugated (ConjVL) formulations were prepared and assessed for various stability parameters including cake quality, melting point, liposome reformation, particle size, GLA/QS-21 concentration, presence of ID93, and biological activity for three months in the research laboratory and nine months at ambient temperature in five health centers. Stability assessment for both formulations stored in the research laboratory for three months showed that they were physically stable and biologically active. The field-based ambient stability assessment showed that the formulations maintained physical integrity, liposomal structure, and antigen integrity, with limited chemical degradation of GLA and QS-21 adjuvants observed. ConjVL retains GLA slightly better than the CoVL formulation, and a moderate increase in particle size was observed after nine months. These findings showed that the formulations demonstrate a promising stability profile after extended storage at ambient temperature, suggesting the potential for real-world application without strict refrigeration requirements.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2306-2315"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655523","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":"Ceramide Profiling of Porcine Skin and Systematic Investigation of the Impact of Sorbitan Esters (SEs) on the Barrier Function of the Skin.","authors":"Hans Schoenfelder, Moritz Reuter, Dirk-Heinrich Evers, Michael E Herbig, Dominique Jasmin Lunter","doi":"10.1021/acs.molpharmaceut.4c01245","DOIUrl":"10.1021/acs.molpharmaceut.4c01245","url":null,"abstract":"<p><p>The stratum corneum (SC) lipids provide the main barrier of the skin against the environment. Ceramides make up about half of the lipids by weight and are thus of particular interest. Emulsifiers are used in a multitude of topical formulations, e.g., to stabilize emulsions against coalescence. Investigations showed that some emulsifiers have the potential to impair skin barrier function. Sorbitan esters (SEs) are frequently used emulsifiers in pharmaceutical and cosmetic dermal formulations. Further, cholesterol and lecithin were used as natural alternatives. However, information on their impact on ceramides is very scarce. Thus, we first analyzed the SEs by LC-MS with regard to their composition. Then we developed an LC-MS method to identify and quantify the ceramides in porcine skin and subsequently investigated the impact of emulsifiers on the ceramide profile. Besides the LC-MS measurements, the effect of emulsifiers on the skin barrier function was investigated by trans-epidermal water loss (TEWL) measurements and confocal Raman spectroscopy (CRS). Throughout the experiments, water was used as a negative control and sodium lauryl sulfate (SLS) as a positive control. It was found that SEs are mixtures of mono-, di-, and triesters, partially with a complex fatty acid distribution. LC-MS measurements of the total ceramide content of the SC samples revealed the SE 60 and cholesterol-treated samples to be those showing the least ceramide depletion, implying a high skin tolerability in general. The TEWL measurements showed that SEs 40, 60, 80, and 120 showed no significant changes in skin barrier function. The lipid content, measured by CRS, was mostly decreased except for SE 120. Conformation, chain order, and SC thickness, also measured by CRS, showed no significant differences. These detailed investigations lead to the view that SEs are skin-friendly substances and can be used for topical applications, e.g., those commonly used to treat skin diseases.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2019-2028"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603143","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":"Biopharmaceutics Aspects of Sugar Alcohols: Implementation of Patient-Centricity in Pharmaceutical Development and Clinical Use.","authors":"Kazuki Matsui","doi":"10.1021/acs.molpharmaceut.4c01309","DOIUrl":"10.1021/acs.molpharmaceut.4c01309","url":null,"abstract":"<p><p>Sugar alcohols such as mannitol and sorbitol are frequently used as pharmaceutical excipients in oral dosage forms. Their versatility stems from extensive evidence of use in humans. However, investigations over many years have clearly indicated their osmolarity-derived biopharmaceutics effects on oral drug absorption. Despite this, these accumulated insights have not been fully integrated into pharmaceutical formulation development or clinical use, leading to suboptimal industrial and clinical practices. This review provides a comprehensive summary of the biopharmaceutics of sugar alcohols, detailing their mechanisms of action and the magnitude of their osmotic effects on the oral absorption of various drugs. Additionally, the review discusses the implications for bioequivalence studies, BCS-based biowaiver guidelines, drug-excipient interactions in pediatric polypharmacy, and pharmaceutical compounding. The aim is to guide future successful and patient-centric pharmaceutical formulation development.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1775-1789"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583949","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":"Crafting a Molecular Trojan Horse: Sialic Acid-Modified PLGA Nanoparticles for Targeted Lung Cancer Therapy.","authors":"Krishan Kumar, Manjit Saini, Varsha Rani, Mohini Mishra, Priya, Jatin, Siddharth Tiwari, Brahmeshwar Mishra, Ruchi Chawla","doi":"10.1021/acs.molpharmaceut.4c00957","DOIUrl":"10.1021/acs.molpharmaceut.4c00957","url":null,"abstract":"<p><p>The glycan receptors prominently expressed on the surface of lung cancer cells offers promising targets for drug delivery. The prepared gemcitabine (GB)-loaded PLGA-NPs and sialic acid (Siac)-modified PLGA-NPs exhibited a uniform polydispersity index (PDI) value below 0.3, a particle size under 200 nm, and negative zeta potentials ranging from -17.45 to -21.45 mV. Entrapment efficiency (% EE) and drug loading values exceeded 70% and 8%, respectively. SEM and TEM showed that the particles were uniformly dispersed with a spherical shape. FTIR, XRD, TGA, and DSC analyses indicated the physiochemical stability of the drug within the nanoformulations. Controlled (26.92 to 31.64% within 24 h at pH 7.4) and pH-sensitive (36.80 to 40.25% within 24 h at pH 5.5) GB release were observed for the different formulations of PLGA-NPs. The MTT cytotoxicity assay revealed IC50 values for the GB control, GB-PLGA-NPs, and GB-PLGA-Siac-NPs as 13.65 ± 1.20, 8.14 ± 1.24, and 4.16 ± 1.05 μg/mL, respectively. The Co6-GB-PLGA-Siac-NPs showed significantly higher cellular uptake than that of the Co6-GB control (<i>p</i> < 0.001) and Co6-GB-PLGA-NPs (<i>p</i> < 0.01) respectively. Pharmacokinetic profiles indicated higher AUC values (ng·h/mL) for GB-PLGA-Siac-NPs (8355.07 ± 2006.45) compared to GB-PLGA-NPs (6145.58 ± 969.25) and the GB control (1510.72 ± 81.08), resulting in higher bioavailability of GB-PLGA-Siac-NPs. Biodistribution studies confirmed superior localization of DiD-GB-PLGA-Siac-NPs, indicated by radiant efficiency signal on B[a]P induced lung cancerous tissues relative to DiD-GB-PLGA-NPs after 1 h (<i>p</i> < 0.001), 4 h (<i>p</i> < 0.01), and 12 h (<i>p</i> < 0.001), which could be attributed to their ability to target glycans. <i>In vivo</i> anticancer efficacy in a B[a]P-induced lung cancer mice model depicted that GB-PLGA-Siac-NPs effectively inhibited lung cancer cells and reduced systemic toxicity, as evidenced by the average number of lung cancer cells, body weight values, survival analysis, biochemical parameters associated with organs (such as the liver and kidney), and histopathological analysis. Therefore, GB-loaded Siac-coated PLGA nanoparticles could serve as an efficient vehicle for GB delivery via targeting glycan receptors in lung cancer therapy.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1816-1830"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530932","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":"Optimization of Immunogenic Cell Death in Triple-Negative Breast Cancer with Virus-like Particle-Based Photothermal Therapy.","authors":"Ryanne N Ehrman, Nancy Tran, Ikeda Trashi, Orikeda Trashi, Thomas S Howlett, Ziqi Wang, Sneha Kumari, Alyssa C Chiev, Jeremiah J Gassensmith","doi":"10.1021/acs.molpharmaceut.4c01059","DOIUrl":"10.1021/acs.molpharmaceut.4c01059","url":null,"abstract":"<p><p>Photothermal therapy (PTT) uses near-infrared (NIR) light and a photothermal agent (PTA) to generate heat to kill tumor cells. PTT is an attractive therapy for highly metastatic tumors─such as triple-negative breast cancer (TNBC)─because PTT is a potent activator of immunogenic cell death (ICD). ICD is characterized by the production of damage-associated molecular patterns (DAMPs) that help the immune system recognize cancer cells as \"nonself.\" This generates an immune response against the tumor cells and helps to combat both primary and metastatic tumors. However, an unknown thermal window remains in which ICD is most prevalent. Here, we conjugate an NIR-absorbing dye to the surface of bacteriophage Qβ to generate a viral-based PTA. Additionally, we demonstrate that mild PTT (<45 °C) is not enough to cause significant apoptosis in the murine TNBC model. In comparison, hot PTT (>60 °C) effectively eliminates cancer cells but is less likely to induce ICD. An optimal temperature range is moderate PTT (50-60 °C), where effective cell killing and ICD occur. We show an increased surface expression of DAMPs within this range, along with an increased ratio of pro- to anti-inflammatory cytokines by dendritic cells.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1881-1891"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565510","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":"Trans-Mediated, Cis-Inhibited Paradoxal Activity of <i>Clostridium perfringens</i> Enterotoxin (c-CPE) in Modulating Epithelial Permeability.","authors":"Julieta M Sanchez, Marianna T P Favaro, Hèctor López-Laguna, Eloi Parladé, Angela Di Somma, Isolda Casanova, Ugutz Unzueta, Ramón Mangues, Esther Vazquez, Eric Voltà-Durán, Antonio Villaverde","doi":"10.1021/acs.molpharmaceut.4c01205","DOIUrl":"10.1021/acs.molpharmaceut.4c01205","url":null,"abstract":"<p><p>In the context of transdermal delivery, favoring the drug permeability of epithelia through convenient formulations would open new opportunities for local versus systemic drug delivery, envisaging higher patient comfort and an enhanced therapeutic effect. Ligands of tight junctions are interesting agents that enhance epithelial permeability by relaxing the protein complexes that form them. The C-terminal domain of <i>Clostridium perfringens</i> enterotoxin (c-CPE), which binds claudins, one of the tight junction (TJ) components, has been explored here as a functional domain in modular recombinant proteins, to evaluate its ability to self-promote its paracellular epithelial passage in a Caco-2 cell monolayer model. c-CPE-containing fusion proteins bind cells in the absence of internalization and cytotoxicity and support the passage, in trans, of other fusion proteins devoid of c-CPE. However, c-CPE-carrying proteins fail to cross the epithelia by themselves, probably because their affinity for TJs immobilizes them in the intercellular space. Therefore, while recombinant c-CPE versions have been here confirmed as convenient epithelial-permeabilizing agents, a paradoxical behavior has been observed where this effect is only successful when applied in trans, specifically on entities that lack c-CPE. Then, c-CPE itself inhibits the paracellular mobility of carrier molecules, not being suited as a self-driver (in c-CPE-drug complexes) for drug delivery through epithelia.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1973-1982"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602944","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":"ImmunoPET Imaging of Trop2 Expression in Bladder Cancer Using [⁶⁴Cu]Cu-NOTA-Trodelvy.","authors":"Wenpeng Huang, Tianyao Wang, Fangfang Chao, Qi Yang, Jason C Mixdorf, Liming Li, Jonathan W Engle, Yu Fan, Lei Kang, Weibo Cai","doi":"10.1021/acs.molpharmaceut.5c00069","DOIUrl":"10.1021/acs.molpharmaceut.5c00069","url":null,"abstract":"<p><p>Trop2 exhibits significantly elevated expression in numerous solid malignancies, playing a crucial role in tumor advancement, whereas its presence in healthy tissues is minimal. In this study, we investigated Trop2 expression in bladder cancer models using [⁶⁴Cu]Cu-NOTA-Trodelvy for immunoPET imaging. In HT-1376 models, [⁶⁴Cu]Cu-NOTA-Trodelvy effectively visualized tumor as early as 12 h p.i. (10.30 ± 1.45% ID/g), with tumor uptake increasing and peaking at 48 h p.i. (13.73 ± 1.16% ID/g), highlighting its potential for tumor imaging. Control groups also demonstrated low tumor uptake (5.27 ± 1.14% ID/g at 48 h in the blocking group; 6.33 ± 0.74% ID/g at 48 h in UM-UC-3; 4.50 ± 0.30% ID/g at 48 h in the [⁶⁴Cu]Cu-NOTA-IgG group). Long-term fluorescence imaging further confirmed the tumor uptake rate in the IRDye 800CW-Trodelvy group was significantly higher than in the IRDye 800CW-Trodelvy blockade group (<i>P</i> < 0.001). Our findings demonstrated that [⁶⁴Cu]Cu-NOTA-Trodelvy enables specific and prolonged tumor accumulation in bladder cancer models, providing precise and noninvasive monitoring of Trop2 expression.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2266-2275"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11978314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583951","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}