Molecular PharmaceuticsPub Date : 2024-09-02Epub Date: 2024-08-01DOI: 10.1021/acs.molpharmaceut.4c00493
Joyann A Marks, Brittany L B Nichols, Laura I Mosquera-Giraldo, Sara T Yazdi, Lynne S Taylor, Kevin J Edgar
{"title":"6-Carboxycellulose Acetate Butyrate: Effectiveness as an Amorphous Solid Dispersion Polymer.","authors":"Joyann A Marks, Brittany L B Nichols, Laura I Mosquera-Giraldo, Sara T Yazdi, Lynne S Taylor, Kevin J Edgar","doi":"10.1021/acs.molpharmaceut.4c00493","DOIUrl":"10.1021/acs.molpharmaceut.4c00493","url":null,"abstract":"<p><p>Amorphous solid dispersion (ASD) in a polymer matrix is a powerful method for enhancing the solubility and bioavailability of otherwise crystalline, poorly water-soluble drugs. 6-Carboxycellulose acetate butyrate (CCAB) is a relatively new commercial cellulose derivative that was introduced for use in waterborne coating applications. As CCAB is an amphiphilic, carboxyl-containing, high glass transition temperature (<i>T</i><sub><i>g</i></sub>) polymer, characteristics essential to excellent ASD polymer performance, we chose to explore its ASD potential. Structurally diverse drugs quercetin, ibuprofen, ritonavir, loratadine, and clarithromycin were dispersed in CCAB matrices. We evaluated the ability of CCAB to create ASDs with these drugs and its ability to provide solubility enhancement and effective drug release. CCAB/drug dispersions prepared by spray drying were amorphous up to 25 wt % drug, with loratadine remaining amorphous up to 50% drug. CCAB formulations with 10% drug proved effective at providing <i>in vitro</i> solubility enhancement for the crystalline flavonoid drug quercetin as well as ritonavir, but not for the more soluble APIs ibuprofen and clarithromycin and the more hydrophobic loratadine. CCAB did provide slow and controlled release of ibuprofen, offering a simple and promising Long-duration ibuprofen formulation. Formulation with clarithromycin showed the ability of the polymer to protect against degradation of the drug at stomach pH. Furthermore, CCAB ASDs with both loratadine and ibuprofen could be improved by the addition of the water-soluble polymer poly(vinylpyrrolidone) (PVP), with which CCAB shows good miscibility. CCAB provided solubility enhancement in some cases, and the slower drug release exhibited by CCAB, especially in the stomach, could be especially beneficial, for example, in formulations containing known stomach irritants like ibuprofen.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873557","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}
Molecular PharmaceuticsPub Date : 2024-09-02Epub Date: 2024-08-12DOI: 10.1021/acs.molpharmaceut.4c00368
Sarah C Erlandson, Jialu Wang, Haoran Jiang, James Osei-Owusu, Howard A Rockman, Andrew C Kruse
{"title":"Engineering and Characterization of a Long-Half-Life Relaxin Receptor RXFP1 Agonist.","authors":"Sarah C Erlandson, Jialu Wang, Haoran Jiang, James Osei-Owusu, Howard A Rockman, Andrew C Kruse","doi":"10.1021/acs.molpharmaceut.4c00368","DOIUrl":"10.1021/acs.molpharmaceut.4c00368","url":null,"abstract":"<p><p>Relaxin-2 is a peptide hormone with important roles in human cardiovascular and reproductive biology. Its ability to activate cellular responses such as vasodilation, angiogenesis, and anti-inflammatory and antifibrotic effects has led to significant interest in using relaxin-2 as a therapeutic for heart failure and several fibrotic conditions. However, recombinant relaxin-2 has a very short serum half-life, limiting its clinical applications. Here, we present protein engineering efforts targeting the relaxin-2 hormone in order to increase its serum half-life while maintaining its ability to activate the G protein-coupled receptor RXFP1. To achieve this, we optimized a fusion between relaxin-2 and an antibody Fc fragment, generating a version of the hormone with a circulating half-life of around 3 to 5 days in mice while retaining potent agonist activity at the RXFP1 receptor both in vitro and in vivo.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141969992","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}
Molecular PharmaceuticsPub Date : 2024-09-02Epub Date: 2024-08-09DOI: 10.1021/acs.molpharmaceut.4c00469
Tangna Hao, Weiwei Jiang, Lei Qian, Xianxian Yang, Wenjing Li, Bingning Zhang, Yunan Li, Zhen Li
{"title":"Coadministration of Quercetin and Indocyanine Green via PEGylated Phospholipid Micelles for Augmented Chem-Photothermal Combination Tumor Therapy.","authors":"Tangna Hao, Weiwei Jiang, Lei Qian, Xianxian Yang, Wenjing Li, Bingning Zhang, Yunan Li, Zhen Li","doi":"10.1021/acs.molpharmaceut.4c00469","DOIUrl":"10.1021/acs.molpharmaceut.4c00469","url":null,"abstract":"<p><p>A significant impediment persists in developing multicomponent nanomedicines designed to dismantle the heat shock protein (HSP)-based protective mechanism of malignant tumors during photothermal therapy. Herein, well-defined PEGylated phospholipid micelles were utilized to coencapsulate quercetin (QUE, a natural anticancer agent and potent HSP inhibitor) and indocyanine green (ICG, a photothermal agent) with the aim of achieving synchronized and synergistic drug effects. The subsequent investigations validated that the tailored micellar system effectively enhanced QUE's water solubility and augmented its cellular internalization efficiency. Intriguingly, the compositional PEGylated phospholipids induced extraordinary endoplasmic reticulum stress, thereby sensitizing the tumor cells to QUE. Furthermore, QUE played a crucial role in inhibiting the stress-induced overexpression of HSP70, thereby augmenting the photothermal efficacy of ICG. In systemic applications, the proposed nanotherapeutics exhibited preferential accumulation within tumors and exerted notable tumoricidal effects against 4T1 xenograft tumors under 808 nm near-infrared irradiation, facilitated by prominent near-infrared fluorescence imaging-guided chemo-photothermal therapy. Therefore, our strategy for fabricating multicomponent nanomedicines emerges as a coordinated platform for optimizing antitumor therapeutic efficacy and offers valuable insights for diverse therapeutic modalities.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905010","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}
Molecular PharmaceuticsPub Date : 2024-09-02Epub Date: 2024-08-06DOI: 10.1021/acs.molpharmaceut.4c00670
Mihaela Tuksar, Edi Topić, Mirta Rubčić, Ernest Meštrović
{"title":"Exploring Salts of Memantine with Inorganic Anions: From Polymorphism and Solid-State Transitions to Potential for Drug Formulations.","authors":"Mihaela Tuksar, Edi Topić, Mirta Rubčić, Ernest Meštrović","doi":"10.1021/acs.molpharmaceut.4c00670","DOIUrl":"10.1021/acs.molpharmaceut.4c00670","url":null,"abstract":"<p><p>This study examines pharmaceutically acceptable inorganic salts of memantine, specifically focusing on hydrogen sulfate, sulfate, and dihydrogen phosphate salts, with the aim of finding alternatives to the commonly used chloride salt in the treatment of Alzheimer's disease. Through comprehensive solid-state characterization, including powder X-ray diffraction, thermal analysis, and solubility testing, we unveil complex polymorphic behaviors, reversible solid-state transitions, and significant differences in solubility and stability among the salts. Notably, the hydrogen sulfate salt emerges as a promising candidate for drug formulations, offering improved solubility, nonhygroscopic nature, and favorable morphological characteristics compared to the existing chloride salt. This work establishes a foundation for further investigation into memantine salts as potential therapeutics with improved efficacy.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896103","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}
Molecular PharmaceuticsPub Date : 2024-09-02Epub Date: 2024-07-29DOI: 10.1021/acs.molpharmaceut.4c00366
Qiang Wan, Hongmei Yuan, Ping Cai, Yang Liu, Ting Yan, Li Wang, Zhijun Zhou, Wei Zhang, Nan Liu
{"title":"Effects of PEGylation on Imaging Contrast of <sup>68</sup>Ga-Labeled Bicyclic Peptide PET Probes Targeting Nectin-4.","authors":"Qiang Wan, Hongmei Yuan, Ping Cai, Yang Liu, Ting Yan, Li Wang, Zhijun Zhou, Wei Zhang, Nan Liu","doi":"10.1021/acs.molpharmaceut.4c00366","DOIUrl":"10.1021/acs.molpharmaceut.4c00366","url":null,"abstract":"<p><p>Nectin cell adhesion molecule 4 (Nectin-4) is overexpressed in various malignant tumors and has emerged as a promising target for tumor imaging. Bicyclic peptides, known for their conformational rigidity, metabolic stability, and membrane permeability, are ideal tracers for positron emission tomography (PET) imaging. In this study, we evaluated the feasibility of visualizing Nectin-4-positive tumors using radiolabeled bicyclic peptide derivatives and optimized the pharmacokinetics of radiotracers by introducing PEG chains of different lengths. Five PEGylated radiotracers radiolabeled with <sup>68</sup>Ga<sup>3+</sup> exhibited high radiochemical purity and stability. As the chain length increased, the Log <i>D</i> values decreased from -2.32 ± 0.13 to -2.50 ± 0.16, indicating a gradual increase in the hydrophilicity of the radiotracers. In vitro cell-binding assay results showed that the PEGylated bicyclic peptide exhibits nanomolar affinity, and blocking experiments confirmed the specific binding of the tracers to the Nectin-4 receptor. In vivo PET imaging and biodistribution studies in SW780 and 5637 xenograft mice showed that [<sup>68</sup>Ga]Ga-NOTA-PEG<sub>12</sub>-BP demonstrated optimal pharmacokinetics, characterized by rapid and good tumor uptake, faster background clearance, and improved tumor-to-tissue contrast. Finally, compared with <sup>18</sup>F-FDG, PET imaging, in vivo blocking assays of [<sup>68</sup>Ga]Ga-NOTA-PEG<sub>12</sub>-BP and histological staining confirmed that specific tumor uptake was mediated by Nectin-4 receptors. The results indicated that [<sup>68</sup>Ga]Ga-NOTA-PEG<sub>12</sub>-BP was a promising PET radiotracer for Nectin-4 targeting, with applications for clinical translation.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786476","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}
Molecular PharmaceuticsPub Date : 2024-09-02Epub Date: 2024-07-30DOI: 10.1021/acs.molpharmaceut.4c00342
Ivan Antolović, Jadran Vrabec, Martin Klajmon
{"title":"COSMOPharm: Drug-Polymer Compatibility of Pharmaceutical Amorphous Solid Dispersions from COSMO-SAC.","authors":"Ivan Antolović, Jadran Vrabec, Martin Klajmon","doi":"10.1021/acs.molpharmaceut.4c00342","DOIUrl":"10.1021/acs.molpharmaceut.4c00342","url":null,"abstract":"<p><p>The quantum mechanics-aided COSMO-SAC activity coefficient model is applied and systematically examined for predicting the thermodynamic compatibility of drugs and polymers. The drug-polymer compatibility is a key aspect in the rational selection of optimal polymeric carriers for pharmaceutical amorphous solid dispersions (ASD) that enhance drug bioavailability. The drug-polymer compatibility is evaluated in terms of both solubility and miscibility, calculated using standard thermodynamic equilibrium relations based on the activity coefficients predicted by COSMO-SAC. As inherent to COSMO-SAC, our approach relies only on quantum-mechanically derived σ-profiles of the considered molecular species and involves no parameter fitting to experimental data. All σ-profiles used were determined in this work, with those of the polymers being derived from their shorter oligomers by replicating the properties of their central monomer unit(s). Quantitatively, COSMO-SAC achieved an overall average absolute deviation of 13% in weight fraction drug solubility predictions compared to experimental data. Qualitatively, COSMO-SAC correctly categorized different polymer types in terms of their compatibility with drugs and provided meaningful estimations of the amorphous-amorphous phase separation. Furthermore, we analyzed the sensitivity of the COSMO-SAC results for ASD to different model configurations and σ-profiles of polymers. In general, while the free volume and dispersion terms exerted a limited effect on predictions, the structures of oligomers used to produce σ-profiles of polymers appeared to be more important, especially in the case of strongly interacting polymers. Explanations for these observations are provided. COSMO-SAC proved to be an efficient method for compatibility prediction and polymer screening in ASD, particularly in terms of its performance-cost ratio, as it relies only on first-principles calculations for the considered molecular species. The open-source nature of both COSMO-SAC and the Python-based tool COSMOPharm, developed in this work for predicting the API-polymer thermodynamic compatibility, invites interested readers to explore and utilize this method for further research or assistance in the design of pharmaceutical formulations.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791326","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}
Molecular PharmaceuticsPub Date : 2024-09-02Epub Date: 2024-08-13DOI: 10.1021/acs.molpharmaceut.4c00322
Liming Zheng, Honghong Song, Yang Li, Hengfei Li, Guanlin Lin, Zhenyu Cai
{"title":"Insulin-Induced Gene 1-Enhance Secretion of BMSC Exosome Enriched in miR-132-3p Promoting Wound Healing in Diabetic Mice.","authors":"Liming Zheng, Honghong Song, Yang Li, Hengfei Li, Guanlin Lin, Zhenyu Cai","doi":"10.1021/acs.molpharmaceut.4c00322","DOIUrl":"10.1021/acs.molpharmaceut.4c00322","url":null,"abstract":"<p><p>Chronic diabetic wounds represent a significant clinical challenge because of impaired healing processes, which require innovative therapeutic strategies. This study explores the therapeutic efficacy of insulin-induced gene 1-induced bone marrow mesenchymal stem cell exosomes (Insig1-exos) in promoting wound healing in diabetic mice. We demonstrated that Insig1 enhanced the secretion of bone marrow mesenchymal stem cell-derived exosomes, which are enriched with miR-132-3p. Through a series of in vitro and in vivo experiments, these exosomes significantly promoted the proliferation, migration, and angiogenesis of dermal fibroblasts under high-glucose conditions. They also regulated key wound-healing factors, including matrix metalloproteinase-9, platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor-β1, and platelet endothelial cell adhesion molecule-1, thereby accelerating wound closure in diabetic mice. Histological analysis showed that Insig1-exos were more effective in promoting epithelialization, enhancing collagen deposition, and reducing inflammation. Additionally, inhibition of miR-132-3p notably diminished these therapeutic effects, underscoring its pivotal role in the wound-healing mechanism facilitated by Insig1-exos. This study elucidates the molecular mechanisms through which Insig1-exos promotes diabetic wound healing, highlighting miR-132-3p as a key mediator. These findings provide new strategies and theoretical foundations for treating diabetes-related skin injuries.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970021","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}
Molecular PharmaceuticsPub Date : 2024-09-02Epub Date: 2024-07-26DOI: 10.1021/acs.molpharmaceut.4c00297
Jisun Lee, Bomi Kim, Hye-Min Woo, Jun-Won Kim, Inji Jung, Seong-Wook Park, Yong-Sung Kim, Jung-Hyun Na, Sang Taek Jung
{"title":"Enhanced Omicron Variant Neutralization by a Human Antibody Tailored to Wild-Type and Delta-Variant SARS-CoV-2 RBDs.","authors":"Jisun Lee, Bomi Kim, Hye-Min Woo, Jun-Won Kim, Inji Jung, Seong-Wook Park, Yong-Sung Kim, Jung-Hyun Na, Sang Taek Jung","doi":"10.1021/acs.molpharmaceut.4c00297","DOIUrl":"10.1021/acs.molpharmaceut.4c00297","url":null,"abstract":"<p><p>Given the previous SARS-CoV-2 pandemic and the inherent unpredictability of viral antigenic drift and shift, preemptive development of diverse neutralizing antibodies targeting a broad spectrum of epitopes is essential to ensure immediate therapeutic and prophylactic interventions during emerging outbreaks. In this study, we present a monoclonal antibody engineered for cross-reactivity to both wild-type and Delta RBDs, which, surprisingly, demonstrates enhanced neutralizing activity against the Omicron variant despite a significant number of mutations. Using an <i>Escherichia coli</i> inner membrane display of a human naïve antibody library, we identified antibodies specific to the wild-type SARS-CoV-2 receptor binding domain (RBD). Subsequent directed evolution via yeast surface display yielded JS18.1, an antibody with high binding affinity for both the Delta and Kappa RBDs, as well as enhanced binding to other RBDs (wild-type, Alpha, Beta, Gamma, Kappa, and Mu). Notably, JS18.1 (engineered for wild-type and Delta RBDs) exhibits enhanced neutralizing capability against the Omicron variant and binds to RBDs noncompetitively with ACE2, distinguishing it from other previously reported antibodies. This underscores the potential of pre-existing antibodies to neutralize emerging SARS-CoV-2 strains and offers insights into strategies to combat emerging viruses.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755723","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}
Molecular PharmaceuticsPub Date : 2024-09-02Epub Date: 2024-07-30DOI: 10.1021/acs.molpharmaceut.4c00092
Chenxu Shao, Xiaoping Yan, Hui Li, Di Nian, Li Ren, Shangjie Pang, Junjie Sun
{"title":"Intranuclear Irradiation Inhibits Solid Tumor Growth by Upregulating Caspase8 and Activating Apoptosis.","authors":"Chenxu Shao, Xiaoping Yan, Hui Li, Di Nian, Li Ren, Shangjie Pang, Junjie Sun","doi":"10.1021/acs.molpharmaceut.4c00092","DOIUrl":"10.1021/acs.molpharmaceut.4c00092","url":null,"abstract":"<p><p>Radioimmunotherapy (RIT) is a novel and promising cancer treatment method, with ongoing research focusing on RIT antibody selection, radionuclides, treatment options, and benefited patient groups. As we dive into the mechanisms of tumor biology, a deeper exploration of how RIT affects tumor tissue is needed to provide new ways to improve clinical treatment outcome and patient prognosis. We labeled the anti-PD-L1 monoclonal antibody atezolizumab with iodine-131 (<sup>131</sup>I), separated and purified the labeled mAb with Sephadex G-25 medium gel filtration resin, and tested product stability. We detected the in vivo activity of <sup>131</sup>I-PD-L1 mAb by analyzing its in vivo biodistribution and performing SPECT imaging and then set different treatment groups to study the effect of <sup>131</sup>I-atezolizumab on the survival of tumor-bearing mice. Western blot, real-time quantitative PCR, and immunohistochemistry were used to detect the expression level of Caspase8 and Nlrp3 in tumor. TUNEL fluorescence staining was used to detect the apoptosis in the tumor. The radiopharmaceutical molecular probe <sup>131</sup>I-atezolizumab showed high stability and in vivo biological activity. The treatment regimen adopted had a positive effect on the survival of tumor-bearing mice. <sup>131</sup>I internal irradiation upregulated Caspase8 in tumor and ultimately inhibited solid tumor growth by activating apoptosis pathways. We also found a significant increase in the expression of NLRP3, which plays an important role in the pyroptosis pathway, in tumor. In summary, our data demonstrated that radiopharmaceuticals combined with immunotherapy affected tumor tissue by modulating relevant biological pathways, thereby achieving better antitumor effects compared with single therapy and providing new insights for promoting better patient prognosis and combination treatment strategies.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791327","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}