Molecular Pharmaceutics最新文献

{"title":"Evaluation of a Novel Gd-FAPI Dimer Molecular Probe Targeting Fibroblast Activation Protein for Imaging of Solid Tumors.","authors":"Xiaohui Wang, Caiyu Zhuang, Xinhui Zheng, Xiaolei Zhang, Zhijian Han, Renhua Wu","doi":"10.1021/acs.molpharmaceut.4c01175","DOIUrl":"10.1021/acs.molpharmaceut.4c01175","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment. Fibroblast activation protein (FAP) is overexpressed in CAFs. FAP-targeted molecular imaging agents, including the FAP inhibitors (FAPIs), have shown promising results in tumor diagnosis. We aimed to design a Gd-labeled FAPI Dimer, Gd-DOTA-Suc-Lys-(FAPI04)₂, to optimize the pharmacokinetics and evaluate its potential capacity for targeting FAP-positive solid tumors in vivo. The Gd-labeled FAPI Dimer was successfully synthesized with exceeding 98% purity. Preclinical pharmacokinetics were determined in assessed FAP-positive U87 cell-derived xenografts and FAP-negative C6-derived xenografts using small-animal T1-weighted 7.0T MR imaging. The longitudinal correlation coefficient (<i>r</i>1) of the agent was 3.813 mM^-1·S^-1. The administration of the Gd-FAPI04 Dimer probe showed a notable enhancement of tumor contrast on T1-weighted whole-body MRI. At 10 and 30 minutes post-injection, the U87 subcutaneous tumor demonstrated significantly greater contrast enhancement than the C6 subcutaneous tumor (<i>P <0.05)</i>. In vivo, the safety of the Gd-FAPI-04 Dimer probe was evaluated, which showed no tissue damage in vital organs like the heart, liver, spleen, lung, and kidneys, as indicated by unchanged morphology compared to a normal saline control group. The novel Gd-FAPI04 Dimer molecular probe, Gd-DOTA-Suc-Lys-(FAPI-04)₂ specifically targeting FAP may serve as a safe and promising tool for the diagnostic imaging of solid tumors.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1498-1506"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381337","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":"Solubility Enhancement of Active Pharmaceutical Ingredients through Liquid Hydrotrope Addition: A Thermodynamic Analysis.","authors":"Sahar Nasrallah, Mirjana Minceva","doi":"10.1021/acs.molpharmaceut.4c01117","DOIUrl":"10.1021/acs.molpharmaceut.4c01117","url":null,"abstract":"<p><p>The poor water solubility of active pharmaceutical ingredients (APIs) poses a significant challenge in pharmaceutical development, affecting their bioavailability and therapeutic efficacy. Consequently, there is an urgent demand for strategies to improve API solubility, with hydrotropy emerging as one of the most effective approaches. Hydrotropes, which can act as excipients in pharmaceutical formulations, enhance solubility by solubilizing hydrophobic compounds in aqueous solutions through mechanisms other than micellar solubilization. However, identifying the right hydrotropic agent requires a screening from a large pool of candidates. This work aims to analyze hydrotropy from a thermodynamic perspective by investigating the influence of the molecular interactions among the API, hydrotrope, and water on the API solubility in water at different temperatures. For this systematic study, hypothetical ternary systems were used and only liquid hydrotropes were considered. Utilizing the Two-Suffix Margules equation to model the liquid phase nonideality, the study revealed that strong API-hydrotrope interactions notably enhance the API solubility in water. Additionally, the interaction between the hydrotrope and water significantly influences API solubility; weaker hydrotrope-water interactions allow for increased API solubility in water. However, when hydrotrope-water interactions are stronger than API-hydrotrope interactions, this effect is diminished. The theoretical findings were validated using solubility experimental data of syringic acid with alkanediols in water from the literature. The results of this work will aid in selecting suitable liquid hydrotropes for enhancing the API solubility in aqueous solutions.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1408-1418"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404903","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":"Development of a Novel ¹⁸F-Labeled Radioligand for Imaging Phosphodiesterase 7 with Positron Emission Tomography.","authors":"Jian Rong, Chunyu Zhao, Ahmad F Chaudhary, Evan Jones, Richard Van, Zhendong Song, Yinlong Li, Jiahui Chen, Xin Zhou, Jimmy S Patel, Yabiao Gao, Zhenkun Sun, Siyan Feng, Zachary Zhang, Thomas L Collier, Chongzhao Ran, Achi Haider, Yihan Shao, Hongjie Yuan, Steven H Liang","doi":"10.1021/acs.molpharmaceut.4c01379","DOIUrl":"10.1021/acs.molpharmaceut.4c01379","url":null,"abstract":"<p><p>Phosphodiesterases (PDEs) are phosphohydrolytic enzymes responsible for degrading cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), two key second messengers involved in regulating cellular functions. The PDE superfamily can be subdivided into 11 families, with PDE7 playing a crucial role in the proinflammatory process, T-cell activation and proliferation. As such, PDE7 has emerged as a potential therapeutic target for treating inflammatory, immunological, and neurological disorders. To date, only a limited number of PDE7 PET ligands have been reported. These ligands often suffer from low <i>in vivo</i> stability or moderate binding affinity, underscoring the need for highly specific PET radioligands for imaging PDE7 <i>in vivo</i>. Here, we report the development of [¹⁸F]<b>7</b> ([¹⁸F]P7-2302<b>)-</b>a highly potent (IC₅₀ = 0.18 nM) and selective (>400 folds over other PDEs) PDE7 PET ligand. <i>In vitro</i> autoradiography studies using rat brain sections revealed high PDE7-specific binding for [¹⁸F]<b>7</b>. Notwithstanding these encouraging findings, PET imaging experiments in rats demonstrated low brain uptake of [¹⁸F]<b>7</b>, potentially owing to brain efflux mechanism. Indeed, <i>in vivo</i> studies with combined P-gp and BCRP inhibition substantially improved brain uptake and enabled us to demonstrate <i>in vivo</i> binding specificity of [¹⁸F]<b>7</b> with PDE<b>7-</b>targeted blockade. Overall, [¹⁸F]<b>7</b> ([¹⁸F]P7-2302<b>)</b> exhibits promising pharmacological properties and chemical scaffold which holds potential as a PDE7-specific PET radioligand, though further work is required to enhance blood-brain barrier permeability.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1657-1666"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456277","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":"Computational Methods for Modeling Lipid-Mediated Active Pharmaceutical Ingredient Delivery.","authors":"Markéta Paloncýová, Mariana Valério, Ricardo Nascimento Dos Santos, Petra Kührová, Martin Šrejber, Petra Čechová, Dimitar A Dobchev, Akshay Balsubramani, Pavel Banáš, Vikram Agarwal, Paulo C T Souza, Michal Otyepka","doi":"10.1021/acs.molpharmaceut.4c00744","DOIUrl":"10.1021/acs.molpharmaceut.4c00744","url":null,"abstract":"<p><p>Lipid-mediated delivery of active pharmaceutical ingredients (API) opened new possibilities in advanced therapies. By encapsulating an API into a lipid nanocarrier (LNC), one can safely deliver APIs not soluble in water, those with otherwise strong adverse effects, or very fragile ones such as nucleic acids. However, for the rational design of LNCs, a detailed understanding of the composition-structure-function relationships is missing. This review presents currently available computational methods for LNC investigation, screening, and design. The state-of-the-art physics-based approaches are described, with the focus on molecular dynamics simulations in all-atom and coarse-grained resolution. Their strengths and weaknesses are discussed, highlighting the aspects necessary for obtaining reliable results in the simulations. Furthermore, a machine learning, i.e., data-based learning, approach to the design of lipid-mediated API delivery is introduced. The data produced by the experimental and theoretical approaches provide valuable insights. Processing these data can help optimize the design of LNCs for better performance. In the final section of this Review, state-of-the-art of computer simulations of LNCs are reviewed, specifically addressing the compatibility of experimental and computational insights.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1110-1141"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062539","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":"Micellar Solvent Accessibility of Esterified Polyoxyethylene Chains as Crucial Element of Polysorbate Oxidation: A Density Functional Theory, Molecular Dynamics Simulation and Liquid Chromatography/Mass Spectrometry Investigation.","authors":"Johanna Weber, Leonardo Pedri, Luis P Peters, Patrick K Quoika, Dennis F Dinu, Klaus R Liedl, Christofer S Tautermann, Tim Diederichs, Patrick Garidel","doi":"10.1021/acs.molpharmaceut.4c01015","DOIUrl":"10.1021/acs.molpharmaceut.4c01015","url":null,"abstract":"<p><p>Given that the amphiphilicity of polysorbates represents a key factor in the protection of proteins from particle formation, the loss of this property through degradative processes is a significant concern. Therefore, the present study sought to identify the factors that contribute to the oxidative cleavage of the polysorbate (PS) molecule and to ascertain the preferred sites of degradation. In order to gain insight into the radical susceptibility of the individual polysorbate segments and their accessibility to water, conceptual density functional theory calculations and molecular dynamics simulations were performed. The behavior of monoesters and diesters was examined in both monomer form and within the context of micelles. The theoretical results were corroborated by experimental findings, wherein polysorbate 20 was subjected to 50 ppb Fe²⁺ and 100,000 lx·h of visible light, and subsequently stored at 25 °C/60% r.h. or 40 °C/75% r.h. for a period of 3 months. Molecular dynamics simulations demonstrated that unesterified polyoxyethylene(POE) chains within a polysorbate 20 molecule exhibited the greatest water accessibility, indicating their heightened susceptibility to oxidation. Nevertheless, the oxidative cleavage of esterified polyoxyethylene chains of a polysorbate 20 molecule is highly detrimental to the protective effect on protein particle formation. This occurs presumably at the oxyethylene (OE) units in the vicinity of the sorbitan ring, leaving a nonamphiphilic molecule in the worst case. Consequently, the critical degradation sites were identified, resulting in the formation of degradation products that indicate a loss of amphiphilicity in PS.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1348-1364"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077959","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":"Meta-Analysis of Permeability Literature Data Shows Possibilities and Limitations of Popular Methods.","authors":"Kateřina Storchmannová, Martin Balouch, Jakub Juračka, František Štěpánek, Karel Berka","doi":"10.1021/acs.molpharmaceut.4c00975","DOIUrl":"10.1021/acs.molpharmaceut.4c00975","url":null,"abstract":"<p><p>Permeability is an important molecular property in drug discovery, as it co-determines pharmacokinetics whenever a drug crosses the phospholipid bilayer, e.g., into the cell, in the gastrointestinal tract, or across the blood-brain barrier. Many methods for the determination of permeability have been developed, including cell line assays (CACO-2 and MDCK), cell-free model systems like parallel artificial membrane permeability assay (PAMPA) mimicking, e.g., gastrointestinal epithelia or the skin, as well as the black lipid membrane (BLM) and submicrometer liposomes. Furthermore, many in silico approaches have been developed for permeability prediction: meta-analysis of publicly available databases for permeability data (MolMeDB and ChEMBL) was performed to establish their usability. Four experimental and two computational methods were evaluated. It was shown that repeatability of the reported permeability measurement is not great even for the same method. For the PAMPA method, two different permeabilities are reported: intrinsic and apparent. They can vary in degrees of magnitude; thus, we suggest being extra cautious using literature data on permeability. When we compared data for the same molecules using different methods, the best agreement was between cell-based methods and between BLM and computational methods. Existence of unstirred water layer (UWL) permeability limits the data agreement between cell-based methods (and apparent PAMPA) with data that are not limited by UWL permeability (computational methods, BLM, intrinsic PAMPA). Therefore, different methods have different limitations. Cell-based methods provide results only in a small range of permeabilities (-8 to -4 in cm/s), and computational methods can predict a wider range of permeabilities beyond physical limitations, but their precision is therefore limited. BLM with liposomes can be used for both fast and slow permeating molecules, but its usage is more complicated than standard transwell techniques. To sum up, when working with in-house measured or published permeability data, we recommend caution in interpreting and combining them.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1293-1304"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466573","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":"Effect of pH and Buffer Capacity of Physiological Bicarbonate Buffer on Precipitation of Drugs.","authors":"Hibiki Yamamoto, Kiyohiko Sugano","doi":"10.1021/acs.molpharmaceut.4c00996","DOIUrl":"10.1021/acs.molpharmaceut.4c00996","url":null,"abstract":"<p><p>The purpose of this study was to investigate the effect of the pH and buffer capacity (β) of physiological bicarbonate buffer solutions (BCB) on drug precipitation. The precipitation profiles of poorly soluble drugs in BCB were evaluated by using a pH-shift precipitation test. Phosphate buffer solutions (PPB) were used for comparison. Two weakly acidic drugs (p<i>K</i>_a: 4.9 and 7.0) and two weakly basic drugs (p<i>K</i>_a: 6.1 and 8.3) were used as model drugs. The bulk phase pH value (pH_bulk) and β values were set to cover the physiological range in the small intestines (pH: 5.5 to 7.5, β: 2.2 to 17.6 mM/ΔpH). A floating lid was used to maintain the pH_bulk of BCB to avoid CO₂ loss. It was also applied to PPB to align the experimental conditions. Each drug was completely dissolved in HCl (pH 3.0, for weakly basic drugs) or NaOH (pH 11.0, for weakly acidic drugs) solutions (450 mL, 50 rpm, 37 °C). The pH_bulk value was then shifted to the neutral pH region by adding a 10-fold concentrated buffer solution (50 mL, final volume of 500 mL). The initial total drug concentration (neutral + ionized species) was set so that the concentration and supersaturation ratio of the neutral species were the same under all pH_bulk conditions. The solid forms of the precipitates were determined by powder X-ray diffraction and differential scanning calorimetry. In BCB, as pH_bulk was increased above (for weakly acidic drugs) or decreased below (for weakly basic drugs) the drug p<i>K</i>_<i>a</i> value, the precipitation of the free form solid became slower. As β was increased, drug precipitation in BCB became faster. Drug precipitation in PPB was faster than that in BCB and less affected by pH_bulk and β. In BCB, at pH_bulk at which a drug is ionizable, the surface pH of the precipitating particles can differ from pH_bulk because of the slow hydration process of CO₂. In conclusion, pH_bulk and β affected the precipitation of weakly acidic and basic drugs in BCB. As BCB is a physiological buffer in the small intestine, it should be used for precipitation studies of weakly acidic and basic drugs.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1318-1328"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077956","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":"Development and Preclinical Assessment of a Palbociclib Nanostructured Lipid Carrier for Potential Breast Cancer Management.","authors":"Nida Nehal, Devika Unnithan, Nasr A Emad, Aashish, Ali Sartaj, Sanjula Baboota, Javed Ali","doi":"10.1021/acs.molpharmaceut.4c01122","DOIUrl":"10.1021/acs.molpharmaceut.4c01122","url":null,"abstract":"<p><p>Breast cancer has the highest incidence rates among all cancers, which represent a global health concern. Effective chemotherapy for breast cancer must minimize adverse effects to improve patient outcomes. Palbociclib (PB), a CDK 4/6 inhibitor, restricts cell growth and suppresses DNA replication in the retinoblastoma tumor suppressor gene (RB). Despite its breakthrough status postapproval, PB is associated with severe side effects, including neutropenia, leukopenia, infections, and thrombocytopenia. The current study aims to develop and optimize a PB-loaded lipidic nanocarrier. The development method was solvent evaporation, and formulation optimization was performed using a central composite rotatable design. Characterization of the nanostructured lipid carrier (NLC) showed a particle size of 129.8 ± 7.6 nm with a PDI of 0.2694 ± 0.04 and a zeta potential of -29.8 ± 2.4 mV. Surface morphology was studied using transmission electron microscopy, which confirmed the particles' uniform and spherical shape. In vitro release studies in 0.1 N HCl and pH 6.8 phosphate buffer demonstrated cumulative drug releases of 91.23 ± 2.1% and 72.9 ± 2.0%, respectively. Intestinal permeation studies demonstrated a 3.76-fold increase in gut permeation with PB-NLC compared to that with PB-Sus. The lipolysis study indicated an enhanced drug availability at the site of absorption. Confocal studies revealed improved drug penetration depth in the intestine with PB-NLC compared to that with PB-Sus. In vivo pharmacokinetic studies demonstrated that incorporating PB into a lipidic nanocarrier (PB-NLC) significantly enhanced its bioavailability by approximately 5.9-fold (<i>p</i> < 0.05) compared to PB suspension. Additionally, acute toxicity studies in Wistar rats confirmed the safety of the developed NLC for oral administration in managing breast cancer. Therefore, the PB-loaded NLC shows significant promise for breast cancer treatment, providing improved drug delivery and minimized side effects.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1419-1436"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363244","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 \"Human Serum Albumin-Platinum(II) Agent Nanoparticles Inhibit Tumor Growth Through Multimodal Action Against the Tumor Microenvironment\".","authors":"Shihang Xu, Weicong Luo, Minghui Zhu, Lei Zhao, Lijuan Gao, Hong Liang, Zhenlei Zhang, Feng Yang","doi":"10.1021/acs.molpharmaceut.5c00050","DOIUrl":"10.1021/acs.molpharmaceut.5c00050","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1725-1726"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077953","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":"Intelligent Design of Lipid Nanoparticles for Enhanced Gene Therapeutics.","authors":"Yichen Yuan, Ying Li, Guo Li, Liqun Lei, Xingxu Huang, Ming Li, Yuan Yao","doi":"10.1021/acs.molpharmaceut.4c00925","DOIUrl":"10.1021/acs.molpharmaceut.4c00925","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) are an effective delivery system for gene therapeutics. By optimizing their formulation, the physiochemical properties of LNPs can be tailored to improve tissue penetration, cellular uptake, and precise targeting. The application of these targeted delivery strategies within the LNP framework ensures efficient delivery of therapeutic agents to specific organs or cell types, thereby maximizing therapeutic efficacy. In the realm of genome editing, LNPs have emerged as a potent vehicle for delivering CRISPR/Cas components, offering significant advantages such as high <i>in vivo</i> efficacy. The incorporation of machine learning into the optimization of LNP platforms for gene therapeutics represents a significant advancement, harnessing its predictive capabilities to substantially accelerate the research and development process. This review highlights the dynamic evolution of LNP technology, which is expected to drive transformative progress in the field of gene therapy.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1142-1159"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057484","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}