Molecular Pharmaceutics最新文献

{"title":"Comprehensive Evaluation of Push-Pull Osmotic Pump Tablets Using Biopredictive Dissolution Tests in Advanced Modular Platform, MRI Visualizations, and Pharmacokinetic Simulations.","authors":"Dorota Danielak, Jadwiga Paszkowska, Larry Martin, Jeffrey Gimbel, David Ferrizzi, Justyna Dobosz, Michał Romański, Ewelina Baran, Piotr Kulinowski, Maciej Winiarski, Michał Smoleński, Marcela Staniszewska, Daria Myslitska, Ali Rajabi-Siahboomi, Grzegorz Garbacz","doi":"10.1021/acs.molpharmaceut.5c00612","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00612","url":null,"abstract":"<p><p>Formulation and manufacturing of push-pull osmotic pump (PPOP) tablets are perceived to be complex technological processes. Multiple factors affect drug release kinetics, including polymer grade, drug-to-osmotic agent ratio, membrane characteristics, and manufacturing methods. In this study, we comprehensively investigated how manufacturing techniques impacted glipizide PPOP tablet performance. PPOP tablets comprised push and drug layers manufactured via wet granulation and/or direct compression methods, and different grades of poly(ethylene oxide) (molecular weights 5000 kDa and 4000 kDa) were used in the push layer. Tablets were characterized using biopredictive dissolution tests in the Advanced Modular Platform (AMP) apparatus under both fasted and fed conditions, simulating physiologically relevant mechanical stress events. Magnetic resonance imaging (MRI) was employed to noninvasively monitor tablet hydration, swelling dynamics, and water distribution in the PPOP during hydration. Physiologically based biopharmaceutics modeling (PBBM) was used to simulate glipizide plasma concentrations. All manufactured PPOP tablets released glipizide similarly, following zero-order kinetics, regardless of the manufacturing method and polymer grade in the push layer. Push and drug layer swelling patterns were also comparable. Under simulated mechanical stress conditions, even those exceeding physiological values, all batches maintained consistent release profiles without dose dumping. Only one batch, with both layers directly compressed, showed slightly slower release under fed conditions, but the PBBM model showed a limited influence on the predicted glipizide plasma concentrations. In conclusion, the manufacturing method and polymer grade had minimal impact on PPOP tablet performance, with direct compression providing a viable alternative to wet granulation. PPOP tablets demonstrated robust resistance to physiologically relevant mechanical stress, confirming their prominent role as controlled drug delivery systems.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751792","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":"Red Blood Cell Membrane-Camouflaged Reduction-Responsive Polyethylenimine-Based Nanoparticles for Enhanced Antitumor Efficacy of Antisense Oligonucleotides.","authors":"Shuang Yang, Beibei He, Cuiping He, Fengye Zhao, Ran Li, Minfei Shi, Bin Zheng","doi":"10.1021/acs.molpharmaceut.5c00412","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00412","url":null,"abstract":"<p><p>As a potential drug, antisense oligonucleotides (AO) have considerable application prospects in the field of tumor treatment. However, the main problem to be solved is the lack of an efficient and safe carrier that contributes to reaching the target cancer cells and utilizing the antitumor effect of AO. Here, we designed and developed a novel AO delivery system, which was based on a modified polyethylenimine (PEI) named TPGS-SS-PEI by connecting tocopherol polyethylene glycol succinate (TPGS) to PEI through the disulfide bond (SS) and the biomimetic red blood cell membrane vesicles (RVs). R-TSP/AO was composed of an AO-loaded micelle (TSP/AO) as the \"core\" prepared by TPGS-SS-PEI, and RVs as the \"shell\". The formulations and properties of R-TSP/AO were optimized and characterized. The mean particle size and zeta potential of R-TSP/AO were 109.7 nm and -24.10 mV, respectively. <i>In vitro</i> studies indicated that R-TSP/AO was sensitive to highly reducing conditions and exhibited excellent stability and high security. In addition, R-TSP showed higher AO transfection efficiency and excellent gene silencing efficiency compared with unmodified PEI (<i>P</i> < 0.001). R-TSP/AO exhibited potent tumor inhibition (55.65%) in 4T1 tumor-bearing mice without inducing systemic toxicity. These findings suggested that R-TSP/AO was safe and efficient in enhancing the antitumor efficacy and R-TSP had the potential to be further researched as a carrier for nucleic acid drugs delivery.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726003","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":"SOX9 siRNA Loaded Lipid Nanoparticles Actively Targeted: Formulation, Delivery, and Antitumor Effect on Colorectal Cancer <i>In Vitro</i> and <i>In Vi</i><i>vo</i>.","authors":"Zhen Zhang, Hongbo Wang, Zhijun Zhang, Yaoyao Zhang, Huajing Sun, Xi Chen, Jiayu Gu, Yanling Gong","doi":"10.1021/acs.molpharmaceut.5c00272","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00272","url":null,"abstract":"<p><p>Small interfering RNA (siRNA)-based therapy, which silences disease-associated genes, has emerged as a potential therapeutic strategy for various disorders, including cancer. Lipid nanoparticles (LNPs) have become a leading platform for efficient siRNA delivery. SOX9, a family member of SRY-related high-mobility-group box (SOX) transcription factors, plays an important role in the pathogenesis and progression of colorectal cancer (CRC). Here, we developed cRGDfK peptide-modificed LNPs (R-LNPs) composed of DLin-MC3-DMA, DMG-PEG, DSPC, DSPE-PEG-cRGDfK, and cholesterol for the targeted delivery of SOX9 siRNA (siSOX9) in CRC treatment. The formulation, delivery, and antitumor effect on CRC <i>in vitro</i> and <i>in vivo</i> were explored. The optimized R-LNPs exhibited favorable physicochemical properties including a uniform particle size (159.6 ± 0.93 nm), low polydispersity index (PDI = 0.207 ± 0.016), near-neutral zeta potential (2.74 ± 0.35 mV), and high encapsulated efficiency (90.71 ± 1.63%). Additionally, R-LNPs demonstrated sustained and controlled <i>in vitro</i> release and good serum stability. The prepared R-LNPs were efficiently uptaken by HCT-116 via clathrin, lipid rafts, and caveolae dependent endocytosis and macropinocytosis. Subsequently, R-LNPs were colocalized with lysosomes before escaping into the cytoplasm, ensuring effective siRNA release. <i>In vivo</i> distribution studies confirmed tumor-specific accumulation for R-LNPs in HCT-116 xenograft models. Functionally, R-LNPs loading siSOX9 inhibited the proliferation, migration, and invasion of HCT-116 cells and Caco-2 cells (<i>P</i> < 0.05 or 0.01) and inhibited tumor growth and proliferation in tumor-bearing mice (<i>P</i> < 0.05 or 0.01). The antitumor effects were attributed to the silence of SOX9, which subsequently downregulated key oncogenic mediators, including β-catenin, cyclin D1, and c-Myc (<i>P</i> < 0.05 or 0.01). Furthermore, R-LNPs demonstrated favorable safety in <i>in vivo</i> application. In conclusion, our cRGDfK-modified LNPs loading siSOX9 represent a promising targeted therapeutic strategy for CRC, offering both efficacy and biocompatibility.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726014","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":"Pharmaceutical Nitrosamines: A Comprehensive Review of Health Risks, Detection, Mitigation Strategies Supplemented with CYP450 Interactions as Molecular Simulations for Mechanistic Insight into Carcinogenicity.","authors":"Kardile Punam Kashinath, Md Samim Sardar, Subhadeep Roy, Anoop Kumar, Santanu Kaity","doi":"10.1021/acs.molpharmaceut.4c01173","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01173","url":null,"abstract":"<p><p>Nitrosamines, identified as unexpected impurities in several drug substances and drug products, have raised significant concern due to their mutagenic and carcinogenic properties. Extensive research has shown that a majority of nitrosamines are potent carcinogens, affecting various organs in multiple species. This article comprehensively analyzes pharmaceutical nitrosamine impurities, their potential health risks, detection, and mitigation strategies, along with a molecular simulation-based exploration of nitrosamine interaction with CYP450 isoforms. The article also explores the chemistry behind nitrosamine formation, their reactions, and the role of cytochrome P450 enzymes in their metabolism. Detection methods like HPLC, LC-MS, and GC-MS, alongside regulatory guidelines from agencies such as the FDA, EMA, ANVISA, TGA, and Health Canada, are discussed in detail. The review further emphasizes the significance of stringent quality control, comprehensive risk assessment methodologies, and effective risk mitigation strategies to address nitrosamine contamination in pharmaceuticals. Nitrosamine impurities require metabolic transformation into electrophiles, which can readily react with DNA and result in mutagenic or carcinogenic effects. This molecular-level understanding can extensively help explore promising nitrosamine scavengers to minimize the chances of possible health hazards due to nitrosamine exposure. Therefore, the interactions of nitrosamine impurities with CYP450 isoforms are explored to get mechanistic insight into carcinogenicity using molecular docking with Xtra precision, along with molecular dynamics studies. Thus, the review provides a detailed spectrum of nitrosamine impurities in pharmaceuticals, covering their sources, toxicological mechanisms, current regulatory overview, risk assessment, and mitigation strategies to ensure drug safety.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705791","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 Reshaping Tumor Blood Vessels to Enhance Drug Penetration with a Multistrategy Synergistic Nanosystem.","authors":"Ying Li, Ying Liu, Bin Du, Genyang Cheng","doi":"10.1021/acs.molpharmaceut.5c01036","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c01036","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705790","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":"Water Mobility and Clustering in Lyophilized Human Serum Albumin.","authors":"Yunhua Chen, Xiaoda Yuan, Shaoxin Feng, Zhiyi Lin, Ehab Moussa, Evgenyi Y Shalaev","doi":"10.1021/acs.molpharmaceut.5c00317","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00317","url":null,"abstract":"<p><p>Water plays a critical role in the stability of lyophilized protein therapeutics by stabilizing protein structures while also contributing to degradation processes like deamidation. Previous studies suggest a critical water threshold where degradation rates change, possibly due to shifts in water distribution between bound and free forms. However, the use of human serum albumin (HSA) as a model to understand the role of water clustering in protein stability has not been systematically explored. Our study examines water distribution, mobility, and clustering in lyophilized HSA using dynamic vapor sorption (DVS), solid-state NMR (ssNMR) spectroscopy, and molecular dynamics (MD) simulations. The water sorption isotherm follows Type II behavior, with Brunauer-Emmett-Teller (BET) analysis indicating a monolayer water content of 6 wt %. MD simulations also show water clusters forming at a similar threshold (∼5.5%). ssNMR analysis reveals increased water mobility between 7.4 and 11.5% water content, marking the transition from bound to free water. Our findings suggest that there is a critical water threshold for lyophilized HSA at 5-6%, where initial clustering occurs, leading to free water with increased mobility (7.4-11.5%). This indicates progressive water interactions and dynamics. This alignment of experimental and modeling data provides a useful insight into the role of water distribution in protein stability in lyophiles. In addition, these results offer a basis for further studies to explore the relationship between water thresholds and protein degradation, with potential applications for optimizing the stability of lyophilized pharmaceutical products.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697114","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":"Rapid Discovery of Potent Neutralizing Antibodies against SARS-CoV-2 through Directed Evolution of SARS-CoV-1 Antibodies.","authors":"Inji Jung, Dinesh Kumar Sriramulu, Jeong Hyeon Yoon, Jisun Lee, Tae Woo Kim, Dae-Hyuk Kweon, Sun-Gu Lee, Sang Taek Jung","doi":"10.1021/acs.molpharmaceut.4c01169","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01169","url":null,"abstract":"<p><p>The emergence of SARS-CoV-1 in 2002 and SARS-CoV-2 in 2019, alongside evolving viral variants, underscores the ongoing threat posed by novel coronaviruses. Monoclonal antibodies have proven effective against these viruses, but most are derived from convalescent patients' B cells, which represent a limited resource during the early stages of an outbreak. This highlights the need for a robust platform to swiftly discover potent virus-neutralizing antibodies. We propose a strategy to leverage pre-existing neutralizing antibodies targeting viruses that utilize the same receptor entry mechanism. Although three anti-SARS-CoV-1 antibodies (80R, m396, and S230) did not bind to the SARS-CoV-2 RBD, we employed bacterial display-based high-throughput directed evolution and successfully isolated two antibodies, IJ4G and IJ225, which exhibited a strong binding affinity to both SARS-CoV-2 wild-type and the Delta variant, demonstrating potent neutralization activity by effectively disrupting ACE2 binding. Notably, these antibodies also retained high binding affinity for the SARS-CoV-1 RBD. Additionally, structural docking models revealed specific amino acid interactions that enabled these engineered antibodies to bind to both SARS-CoV-1 and SARS-CoV-2 RBDs, adapting to the sequence differences between the two. Our findings demonstrate the feasibility of rapidly developing potent neutralizing antibodies using only the virus spike protein sequence during the early stages of virus emergence, offering a promising approach for pandemic preparedness.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705792","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":"Noninvasive Imaging of Early Acute Inflammation with Myeloperoxidase-Specific PET Ligand ⁶⁸Ga-NOTA-3G-bis-5HT.","authors":"Jia Wang, Xiaobo Wang, Meng Niu, Ying Guo, Mingru Zhang, Jiajun Ye, Zifan Zhu, Ruotong Meng, Jing Wang, Fei Kang","doi":"10.1021/acs.molpharmaceut.5c00820","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00820","url":null,"abstract":"<p><p>Myeloperoxidase (MPO), a well-established biomarker of neutrophil activation, plays a crucial role in early acute inflammation. In the study, we developed an MPO-specific PET ligand, ⁶⁸Ga-NOTA-3G-bis-5HT, for noninvasive imaging of early acute inflammation. ⁶⁸Ga-NOTA-3G-bis-5HT was achieved with a radiochemical yield of >70%, radiochemical purity of >95%, and molar activity of 6.10-24.4 GBq/μmol. Molecular docking and molecular dynamics (MD) simulations demonstrated the binding mode and stability between ⁶⁸Ga-NOTA-3G-bis-5HT and MPO with a binding free energy of -75.18 kcal/mol. The <i>in vitro</i> binding assays confirmed the oxidation binding mechanism and high affinity with an IC₅₀ of 1.67 nM. The Matrigel implantation experiment determined the sensitivity of ⁶⁸Ga-NOTA-3G-bis-5HT in the detection of human MPO <i>in vivo</i>. Micro-PET imaging in the mouse model revealed that the accumulation of ⁶⁸Ga-NOTA-3G-bis-5HT in the inflammation site was very rapid and decreased over time within 120 min with an uptake of 1.53 ± 0.11%ID/g and inflammation-to-muscle ratio of 2.67 ± 0.31 at 30 min. Blocking experiments demonstrated the specific binding of ⁶⁸Ga-NOTA-3G-bis-5HT to MPO. Histopathological results further validated MPO expression and neutrophil infiltration in early acute inflammation. The biodistribution manifested a rapid distribution and fast clearance from the body, supporting the favorable pharmacokinetics of ⁶⁸Ga-NOTA-3G-bis-5HT (<i>t</i>_1/2α = 3.55 min and <i>t</i>_1/2β = 24.90 min). Collectively, these findings highlighted the clinical potential of ⁶⁸Ga-NOTA-3G-bis-5HT as a tool for monitoring MPO activity, offering a valuable approach for early acute inflammation diagnosis and risk stratification.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697112","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":"Translational Insights into Stimuli-Responsive Magnetic Nanoparticles for Breast Cancer Treatment.","authors":"Mohammad Sameer Khan, Garima Gupta, Mohammed Ghazwani, Umme Hani, Khang Wen Goh, Prashant Kesharwani","doi":"10.1021/acs.molpharmaceut.5c00473","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00473","url":null,"abstract":"<p><p>Breast cancer (BC) remains the most prevalent malignancy worldwide, predominantly affecting women, and is often accompanied by significant treatment-related side effects. Despite the availability of multiple therapeutic modalities, including chemotherapy, survival rates have shown concerning stagnation or decline. A key limitation of current treatments is their lack of specificity, which leads to off-target toxicity and damage to healthy tissues. In recent years, nanotechnology has emerged as a promising frontier in cancer diagnosis and therapy, offering enhanced precision in drug delivery. Among various nanocarriers, stimuli-responsive magnetic nanoparticles (MNPs) have garnered increasing attention due to their nanoscale size, excellent colloidal stability, high cytocompatibility, and tumor-targeting capabilities. Additionally, MNPs can generate localized hyperthermia upon exposure to an external magnetic field, augmenting their therapeutic efficacy. This review presents a comprehensive analysis of stimuli-responsive MNPs, including their surface functionalization strategies and mechanisms of action in BC therapy. It further highlights recent preclinical advancements, evaluates their therapeutic performance, and discusses relevant patents. Finally, the review explores future perspectives and translational potential, underscoring the role of MNPs in the next generation of BC therapeutics.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697113","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":"Smart Nanometals: An Approach to Transform Brain Cancer Diagnosis and Therapy.","authors":"Anam Arora, Neha Jain, Manisha Pandey, Shreya Kaul, Rupali Verma, Bapi Gorain","doi":"10.1021/acs.molpharmaceut.5c00504","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00504","url":null,"abstract":"<p><p>Cancer is responsible for a great proportion of deaths globally and requires urgent attention. Even with the most recent advanced technologies in diagnosis and interventions, the management and cure of cancer patients are limited. However, novel drug delivery tools with innovative technologies have been shown to deliver chemotherapeutics to cancer cells with minimal interaction with healthy cells. Among them, metallic nanoparticles (MNPs) such as gold, silver, copper oxide, and iron oxide have garnered attention owing to their higher surface area-to-volume ratio, multifunctionality, and tunable optical characteristics, making them suitable for therapeutic, diagnostic, and theranostic purposes in brain carcinoma. It has also been demonstrated that MNPs can maintain significant therapeutic concentrations in target cells through site-specific and continued release. Due to their immense potential, the current review focused on exploring MNPs for improved diagnosis and management of brain tumors. Specifically, this review aimed to understand the interaction of MNPs with the brain tumor microenvironment to overcome impediments such as the blood-brain barrier, efflux pump presence, and the invasive nature of brain tumors. Additionally, the regulatory aspects, existing gaps in research, toxicity concerns, and remediation strategies were addressed to replace traditionally available brain cancer treatment strategies.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688328","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}