Molecular Pharmaceutics最新文献

{"title":"Beyond Correlation: Establishing Causality in Protein Corona Formation for Nanomedicine.","authors":"Arshia Rafieioskouei, Kenneth Rogale, Amir Ata Saei, Morteza Mahmoudi, Borzoo Bonakdarpour","doi":"10.1021/acs.molpharmaceut.5c00262","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00262","url":null,"abstract":"<p><p>In contemporary studies on the role of the protein corona in specific biological applications, identifying <i>correlation</i> is widely used to draw conclusions from observations and statistical methods, yet it merely identifies associations without establishing a direct influence between variables. This over reliance on observation can lead to spurious connections where co-occurrence does not imply causation. In contrast, a <i>causality</i>-focused approach asserts the direct impact of one variable on another, offering a more robust framework for inference and the drawing of scientific conclusions. This approach allows researchers to better predict how changes in a nanoparticle's physicochemical properties or biological conditions will affect protein corona composition and decoration, in turn affecting their safety and therapeutic/diagnostic efficacies. As a proof of concept, we explore the concept of \"actual causality\" (introduced by Halpern and Pearl) to mathematically prove how spiking small molecules, including metabolites, lipids, vitamins, and nutrients, into plasma can induce diverse protein corona patterns on identical nanoparticles. This approach significantly enhances the depth of plasma proteome profiling. Our findings reveal that among the various spiked small molecules, phosphatidylcholine was the actual cause of the observed increase in the proteomic depth of the plasma sample. By considering the concept of causality in the field of protein coronas, the nanomedicine community can substantially improve the ability to design safer and more efficient nanoparticles for both diagnostic and therapeutic purposes.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810098","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 \"Calculating Apparent p<i>K</i>_a Values of Ionizable Lipids in Lipid Nanoparticles\".","authors":"Nicholas B Hamilton, Steve Arns, Mee Shelley, Irene Bechis, John C Shelley","doi":"10.1021/acs.molpharmaceut.5c00402","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00402","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801960","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":"Targeted Radionuclide Therapy of CLDN18.2-Positive Gastric Cancer with [¹³¹I]I-Zolbetuximab: An <i>In Vitro</i> and <i>In Vivo</i> Study.","authors":"Yang Wang, Shuhua He, Lin Ma, Zijun Kuang, Chao Mu, Jian Yang, Yuxia Liu, Zheng Li, Qingnuan Li","doi":"10.1021/acs.molpharmaceut.4c01427","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01427","url":null,"abstract":"<p><p>Radiopharmaceuticals are a promising therapeutic strategy for tumors with less reduced resistance and minimal side effects. In our previous study, we radiolabeled the monoclonal antibody zolbetuximab, which targets CLDN18.2, with ¹²⁵I, and the labeled compound showed favorable tumor targeting and retention. In this research article, [¹³¹I]I-zolbetuximab was prepared to investigate its therapeutic effect on gastric cancer using <i>in vitro</i> and <i>in vivo</i> studies. The zolbetuximab was radiolabeled with ¹³¹I using the Iodogen method. The uptake mechanism of [¹³¹I]I-zolbetuximab was investigated through an endocytosis experiment using MKN45-CLDN18.2 and MKN45 cells. The safety assessment of [¹³¹I]I-zolbetuximab was conducted in normal mice using hematoxylin/eosin (H&E) staining. The tumor uptake, biodistribution, and therapeutic efficacy of [¹³¹I]I-zolbetuximab were evaluated in nude mice bearing MKN45-CLDN18.2 tumors, while the hematological analysis, immunohistochemistry, Western blotting (WB), immunofluorescence, and H&E assays were used to further assess the treatment response and toxicity. [¹³¹I]I-Zolbetuximab exhibited a high labeling efficiency of (96.05 ± 0.23)%, a specific activity of 1.75 × 10² GBq/μmol, and good <i>in vitro</i> stability. The binding of [¹³¹I]I-zolbetuximab to the membrane surface receptors of MKN45-CLDN18.2 cells resulted in significant tumor uptake, retention, and favorable biodistribution in CLDN18.2-positive tumor-bearing nude mice. Safety assessments, including H&E staining, indicated no significant damage to normal mouse organs caused by the labeled compounds. In a therapeutic study involving MKN45-CLDN18.2 tumor-bearing nude mice, increasing drug dose led to notable enhancements in therapeutic efficacy and survival rates. H&E staining of mouse organs at the end of treatment showed no significant toxicity was observed across all dose groups throughout the treatment period. Furthermore, immunohistochemistry, immunoblotting, and immunofluorescence analyses conducted on mouse tumors at the treatment end point demonstrated a reduction in CLDN18.2 expression following treatment. Altogether, [¹³¹I]I-zolbetuximab displayed exceptional targeting capability, tumor retention property, significant therapeutic efficacy, and safety. These findings suggest its potential to serve as a targeted radiopharmaceutical for the treatment of CLDN18.2-positive gastric cancer.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810133","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":"Structural Similarity of Biological Drugs Using Statistical Signal Processing and Nuclear Magnetic Resonance Spectral Pattern Analysis.","authors":"Soumya Ranjan Pujahari, Swpnil Engla, Rohit Soni, Subrata Patra, Manjesh Kumar Hanawal, Ashutosh Kumar","doi":"10.1021/acs.molpharmaceut.5c00108","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00108","url":null,"abstract":"<p><p>Biosimilar drugs are highly similar to the available marketed drugs and have no clinically meaningful differences in terms of safety, purity, and potency. As per stringent drug regulatory requirements, biosimilar drugs must match closely to all attributes of the listed marketed drug, including establishing high similarity of higher-order structures. Here, we have developed a combined approach using high-resolution two-dimensional nuclear magnetic resonance (NMR) spectra and image-based statistical signal processing algorithms to establish robust comparability of critical quality attributes of biological drugs. We have integrated a computational approach to 2D NMR data analysis, which could replace the traditional methods of manually extracting chemical shift values and intensities for each peak and performing a range of statistical analyses, which are laborious and prone to ambiguity. Our algorithm simplifies and streamlines this process, making it more accurate, less time-consuming, and avoiding personal biases. We have employed our methods with a diverse range of biotherapeutics and complex NMR data and shown a degree of similarity between reference and test drugs with our differentially assigned similarity scores.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810127","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":"Molecular Dynamics Simulations of Protein Corona Formation on Membrane Surfaces: Effects of Lipid Composition and PEGylation on Selective Plasma Protein Adsorption.","authors":"Hwankyu Lee","doi":"10.1021/acs.molpharmaceut.4c01533","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01533","url":null,"abstract":"<p><p>The adsorption of plasma proteins (human serum albumin (SA) and apolipoproteins A-I and E-III) onto various lipid bilayers is simulated. With three different binding orientations for each protein, free energy calculations from umbrella sampling simulations show stronger binding of SA to the bilayer composed of lipids with smaller headgroups and stronger binding of apolipoproteins to the bilayer composed of anionic lipids rather than cationic or zwitterionic lipids, in agreement with experiments. Anionic residues of SA form hydrogen bonds more readily with amine headgroups of lipids than with larger trimethylammonium headgroups, where the cationic nitrogen is sterically hindered. In contrast, cationic residues of apolipoproteins form hydrogen bonds predominantly with anionic phosphate groups of lipids, indicating that protein-bilayer binding is attributed to hydrogen bonds facilitated by electrostatic attraction, depending on the electrostatics and size of lipid headgroups. For lipid bilayers grafted with polyethylene glycol (PEG), the binding strength of SA decreases while that of apolipoproteins increases, consistent with experiments, due to hydrogen bonding and hydrophobic interactions between proteins and PEG. These findings help explain experimental observations regarding the abundance of specific plasma proteins adsorbed onto various liposomes and suggest manipulating lipid composition and PEGylation to attract specific proteins to liposome-based drug carriers.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794123","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":"Regulatory and Scientific Complexities in Application of the Proposed Prior Approval Supplement Pathway for Substitution of the Low Global Warming Potential Propellants in the Marketed Metered Dose Inhalers.","authors":"Gur Jai Pal Singh","doi":"10.1021/acs.molpharmaceut.4c01512","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01512","url":null,"abstract":"<p><p>Due to the Greenhouse effect of the hydrofluoroalkane gases, transition of the currently marketed pressurized Metered Dose Inhalers containing these propellants to their new versions with Low Global Warming Potential propellants has been initiated. Both the regulatory authorities and MDI manufacturers are actively engaged in making this transition efficiently and cost-effectively. Traditionally, regulatory approval of propellant changes in MDIs has entailed lengthy and very expensive product development in new drug applications. Recently, however, a Prior Approval Supplement pathway that is commonly used to support scaleup and post approval changes in drug products has been proposed for regulatory submissions to support replacement of the approved hydrofluoroalkane with the MDIs using low global warming potential propellants. However, it is recognized that propellant substitutions in MDIs are not simple excipient changes, as they may influence a variety of critical quality attributes relevant to the safety and efficacy of the inhalers. Therefore, even though the proposal for consideration of propellant substitutions as post approval changes is novel and its regulatory acceptance by the FDA would be revolutionary, its application is complicated in view of the applicable regulatory and scientific considerations. This paper provides an analysis of the regulatory and scientific complexities relevant to the proposed pathway.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 4","pages":"1735-1739"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794129","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":"Investigating the Interaction between Excipients and Monoclonal Antibodies PGT121 and N49P9.6-FR-LS: A Comprehensive Analysis.","authors":"Xun Li, Asuka A Orr, Mohammad M Sajadi, Anthony L DeVico, Daniel J Deredge, Alexander D MacKerell, Stephen W Hoag","doi":"10.1021/acs.molpharmaceut.4c00973","DOIUrl":"10.1021/acs.molpharmaceut.4c00973","url":null,"abstract":"<p><p>N49P9.6-FR-LS and PGT121 are promising antibodies with significant therapeutic potential against HIV infection, but they are prone to precipitation at concentrations greater than 12 to 13 mg/mL. This study evaluates the influence of six excipients─arginine, alanine, sucrose, trehalose, methionine, and glutamate─on the biophysical stability of antibodies. We employed a comprehensive approach, combining computational mAb-excipient interaction analysis via the site-identification by ligand competitive saturation (SILCS) method with extensive experimental characterization. Our experimental matrix included viscosity measurements across temperature gradients, particle size distribution, zeta potential, pH value, and solution appearance, alongside a short-term stability product study at 30 °C and 65% relative humidity, with assessments at t₀ (initial), t₁ (14 days), and t₂ (28 days). Results indicated that sucrose, arginine, alanine, and trehalose provided varying degrees of stabilization for both antibodies. Conversely, glutamate destabilized PGT121 but stabilized N49P9.6-FR-LS, while methionine had a negative effect on N49P9.6-FR-LS but a positive one on PGT121. SILCS-Biologics analysis suggested that stabilization by these excipients is linked to their ability to occupy regions involved in self-protein interactions. Debye-Hückel-Henry charge calculations further indicated that neutral excipients like sucrose and trehalose could alter mAb charges by affecting buffer binding, influencing aggregation propensity. These findings offer valuable insights for optimizing antibody formulations, ensuring enhanced product stability and therapeutic efficacy for HIV treatment.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1831-1846"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539360","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":"E-Urea-K-Based PSMA Imaging Served as an Alternative in Assessing Tumor Neovascularization via Targeting CD31.","authors":"Lan Wang, Shengnan Ren, Jingjing Lou, Shuai Xue, Pan Zhou, Xiaobei Zheng, Fengling Shan, Xiao Li, Yangchun Chen, Xingdang Liu","doi":"10.1021/acs.molpharmaceut.4c01252","DOIUrl":"10.1021/acs.molpharmaceut.4c01252","url":null,"abstract":"<p><p>To reveal the natural correlation between prostate-specific membrane antigen (PSMA) imaging and tumor neovascularization in prostate cancer and further explore E-urea-K-based PSMA-targeted (EK-PSMA) imaging as a potential indicator of tumor neovascularization, the 22Rv1 mouse models were established and underwent ^99mTc-HYNIC-ALUG SPECT/CT. Pearson correlation analysis was applied to assess the relationship between tumor tracer uptake and tumor characteristics, including size, glucose metabolism, and cell phenotypes (e.g., Ki-67, VEGF, CD31, and PSMA). Then, molecular docking further identified the key factors of EK-PSMA imaging, specifically related to tumor neovascularization. Finally, animal models with positive and negative PSMA expression (22Rv1, LNCaP, U87, SAOS-2, A549, and ACHN) were subjected to antibody-targeted blockade to verify the role of these key factors in EK-PSMA imaging. The Pearson's <i>r</i> values of tracer uptake correlated with CD31 and tumor size were 0.82 and 0.99, respectively (<i>P</i> < 0.05), and the correlations of tracer uptake with SUV_max, SUV_mean, Ki-67, VEGF, and PSMA expressions were 0.47, 0.20, 0.69, -0.65, and 0.20, respectively (all <i>P</i> > 0.05). Molecular docking confirmed the affinity of E-urea-K to PSMA (two sites, binding scores, -5.4 kcal/mol and -6.0 kcal/mol) and CD31 (one site, binding score, -5.1 kcal/mol). The blockade of the CD31 antibody partially reduced the ^99mTc-HYNIC-ALUG uptake in five other types of tumors (paired <i>t</i> test, <i>P</i> = 0.0478). The Pearson's <i>r</i> value of CD31 staining and tracer uptake prior to the antibody blockade was 0.84 (<i>P</i> < 0.05). Additionally, when removing the PSMA-positive models (22Rv1 and LNCaP), the Pearson's <i>r</i> value of CD31 staining and tracer uptake prior to the antibody blockade was 0.99 (<i>P</i> < 0.05). Thus, CD31 was found to be a mutual target of EK-PSMA imaging; therefore, EK-PSMA imaging provides a viable assessment option for tumor neovascularization, especially for PSMA-negative tumors.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2029-2039"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514145","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":"Impact of Sugar Molecular Weight on the Miscibility and Stability of Lyophilized and Spray-Dried Protein Formulations.","authors":"Hanh Thuy Nguyen, Mennatallah A Mohamed, Jing Ling, Yong Du, Kevin Kjoller, Yongchao Su, Lynne S Taylor","doi":"10.1021/acs.molpharmaceut.4c01488","DOIUrl":"10.1021/acs.molpharmaceut.4c01488","url":null,"abstract":"<p><p>Poor stability of biological products such as proteins is a major challenge facing the biopharmaceutical industry. Poor stability is usually mitigated by formulating these products in the solid state, employing sugars as stabilizers. Several studies have pointed out the superior stabilizing ability of disaccharides, including sucrose and trehalose, as compared to polysaccharides such as dextrans. The aim of this study was to investigate the impact of excipient molecular weight on miscibility with a model protein, bovine serum albumin (BSA). Aqueous solutions containing a binary combination of a sugar-based stabilizer and BSA were dried using different methods (air drying to form films, spray drying, and lyophilization). The stabilizers tested varied in molecular weight and were dextran 6, 70, or 2000 kDa, hydroxypropyl methyl cellulose (HPMC), and trehalose. Miscibility was evaluated using a variety of techniques including confocal fluorescence microcopy, infrared and Raman microscopy, and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. The stability of BSA in dried mixtures subjected to accelerated storage conditions was also measured. BSA was more stable in the presence of dextran 2000 kDa compared to dextran 70 and 6 kDa, while stability was highest in trehalose and lowest in HPMC. From ssNMR spectroscopy, BSA-Dex 2000 kDa and BSA-trehalose were miscible over 20 and 5 nm length scales, BSA-Dex 6 kDa was miscible over a 20 nm length scale and phase-separated over a 5 nm length scale, while BSA-Dex 70 kDa and BSA-HPMC were phase-separated over both length scales. It was postulated that for dextran, the size of the polysaccharide relative to the size of the protein determined the extent of the system miscibility and stability. A smaller or similar polysaccharide size compared to that of the protein, as in the case of BSA-Dex 6 kDa and BSA-Dex 70 kDa, leads to depletion-induced phase separation. A much larger polysaccharide size compared to that of the protein allows the protein molecules to be trapped within a polysaccharide mesh, resulting in a miscible system. This study suggests that the impact of the relative size of the stabilizer and protein on miscibility is more complex than previously considered.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2233-2245"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565509","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":"Suppression of Liver Fibrogenesis with Photothermal Sorafenib Nanovesicles via Selectively Inhibiting Glycolysis and Amplification of Active HSCs.","authors":"Xianjing Xiang, Yaru Shao, Li Xiang, Qiangqiang Jiao, Wenhui Zhang, Yuting Qin, Yuping Chen","doi":"10.1021/acs.molpharmaceut.4c01135","DOIUrl":"10.1021/acs.molpharmaceut.4c01135","url":null,"abstract":"<p><p>As the major driving factor of hepatic fibrosis, the activated hepatic stellate cells (aHSCs) rely on active glycolysis to support their aberrant proliferation and secretion of the extracellular matrix. Sorafenib (Sor) can combat liver fibrosis by suppressing HIF-1α and glycolysis, but its poor solubility, rapid metabolism, and low bioavailability restrict such a clinical application. Here, Sor was loaded onto polydopamine nanoparticles and then encapsulated by a retinoid-decorated red blood cell membrane, yielding HSC-targeted Sor nanovesicles (PDA/Sor@RMV-VA) with a high Sor-loading capacity and photothermally controlled drug release for antifibrotic treatment. These Sor RMVs not only exhibited a good particle size, dispersity and biocompatibility, prolonged circulation time, enhanced aHSC targetability, and hepatic accumulation both in vitro and in vivo, but also displayed a mild photothermal activity proper for promoting sorafenib release and accumulation in CCl₄-induced fibrotic mouse livers without incurring phototoxicity. Compared with nontargeting Sor formulations, PDA/Sor@RMV-VA more effectively downregulated HIF-1α and glycolytic enzyme in both cultured aHSCs and fibrotic mice and reversed myofibroblast phenotype and amplification of aHSCs and thus more significantly improved liver damage, inflammation, and fibrosis, all of which could be even further advanced with NIR irradiation. These results fully demonstrate the antifibrotic power and therapeutic potential of PDA/Sor@RMV-VA as an antifibrotic nanomedicine, which would support a new clinical treatment for hepatic fibrosis.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1939-1957"},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571564","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}