Molecular Pharmaceutics最新文献

{"title":"Influence of Pore Size of Mesoporous Silica on Physical Stability of Overloaded Celecoxib Glass.","authors":"Xue Han, Kohsaku Kawakami","doi":"10.1021/acs.molpharmaceut.4c01482","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01482","url":null,"abstract":"<p><p>The stabilization mechanism of mesoporous silica (MS) of two different pore sizes (21 and 2.5 nm) on overloaded celecoxib (CEL) glass was investigated. Differential scanning calorimetry (DSC) measurements revealed the presence of three fractions with different molecular mobilities: free, intermediate, and rigid ones. The free fraction exhibited cold crystallization during DSC heating and was assumed to have almost the same properties as those of the bulk molecules. The rigid fraction did not exhibit either glass transition or cold crystallization behavior, which should be stabilized by interactions with the MS surface. The remaining molecules exhibited glass transition behavior without any tendency toward cold crystallization during heating, which is called the intermediate fraction. The molecular dynamics of each fraction was investigated by using broadband dielectric spectroscopy (BDS). While the intermediate and free fractions exhibited comparable mobility, the rigid fraction demonstrated pore-size-dependent behavior: enhanced and suppressed molecular mobility was observed for the rigid fraction confined in 21 and 2.5 nm-pores, respectively. Isothermal crystallization of CEL glass was investigated using DSC and BDS at 95 °C. The results revealed that the CEL glass mixed with MS with large pores exhibited slower crystallization compared to the CEL glass without MS, whereas accelerated crystallization was observed for the CEL mixed with a small amount of MS of small pores. The pore size of 21 nm was much larger than the cooperatively rearranging region (CRR) of the CEL glass, whereas the pore size of 2.5 nm was comparable to that. When the pore size was larger than that of the CRR, most of the loaded CEL molecules behaved as an intermediate fraction, presumably because the molecules could exchange inside and outside the pore. In contrast, the exchange was not likely to proceed when the pore size was comparable to or smaller than that of the CRR, leaving a large free fraction. This finding provides a deep understanding of the stabilization mechanism of overloaded pharmaceutical glass by using mesoporous materials.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778624","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":"Protamine-Based Nanotherapeutics for Gene Delivery to Glioblastoma Cells.","authors":"Sheila Barrios-Esteban, Sonia Reimóndez-Troitiño, Pablo Cabezas-Sainz, María de la Fuente, Laura Sánchez, Ruman Rahman, Cameron Alexander, Marcos Garcia-Fuentes, Noemi S Csaba","doi":"10.1021/acs.molpharmaceut.4c01269","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01269","url":null,"abstract":"<p><p>Isocitrate dehydrogenase wild-type glioblastoma is the most aggressive primary brain tumor classified as grade 4 of malignancy. Standard treatment, combining surgical resection, radiotherapy, and chemotherapy, often leads to severe side effects, with the emergence of tumor recurrence in all cases. Nucleic acid-based therapy has emerged as a promising strategy for cancer treatment. Non-viral nanosystems have become the vehicles of choice for gene delivery, due to their efficient nucleic acid encapsulation, protection, and intracellular transport. This work explores the potential of a formulation of low molecular weight protamine (LMWP) and dextran sulfate for gene delivery. The nanoparticles (NPs) were evaluated in terms of particle size, surface charge, morphology, and capacity to condense different nucleic acids. NPs formed by ionic complexation resulted in a homogeneous population of spherical particles with a low polydispersity index (PDI), small size, and positive surface charge. Competitive displacement assay demonstrated that the NPs could condense nucleic acids without alterations in their morphology and physicochemical characteristics, even after long-term storage. The efficacy of this formulation as a gene delivery system was evaluated <i>in vitro</i> in different glioblastoma cell lines and three-dimensional (3D) spheroids and <i>in vivo</i> using zebrafish models, showing negligible toxicity, efficient internalization, and consistent expression of fluorescent/luminescent proteins. Overall, these cationic polymeric NPs show promising features for their use as non-viral gene delivery vehicles for glioblastoma treatments.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770743","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":"BODIPY-Based Photothermal Agent Incorporating Azulene for Enhanced NIR Absorption and Tumor Ablation.","authors":"Kai Nishimura, Mikiya Kato, Tomoya Fukui, Kazuki Miura, Masato Tsuda, Satoshi Okada, Takanori Fukushima, Hiroyuki Nakamura","doi":"10.1021/acs.molpharmaceut.5c00071","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00071","url":null,"abstract":"<p><p>Photothermal therapy (PTT) is a promising minimally invasive treatment that converts light energy into localized heat for tumor ablation. Indocyanine green (ICG), the only clinically approved photothermal agent (PTA), suffers from rapid photobleaching and poor tumor retention, underscoring the urgent need for next-generation PTAs with improved properties. In this study, we report AzuGlu-BODIPY, a novel azulene-containing BODIPY-based PTA incorporating 1,2,3,4-tetrahydroquinoline and glucose, designed to overcome these limitations. AzuGlu-BODIPY demonstrates a high photothermal conversion efficiency (PCE) of 51%, effective near-infrared (NIR) absorption, and thermal stability in both dimethyl sulfoxide (DMSO) and aqueous solutions. <i>In vitro</i> studies revealed potent photothermal efficacy against cancer cell lines, with IC₅₀ values of 3.1-4.6 μM under 808 nm laser irradiation, while <i>in vivo</i> experiments showed complete tumor regression in 4T1 tumor-bearing mice following localized administration and laser treatment. These results suggest AzuGlu-BODIPY as a promising PTA and provide a versatile platform for advancing azulene-based PTAs with enhanced functionality for PTT.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750279","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":"Role of Microneedles for Improved Treatment of Obesity: Progress and Challenges.","authors":"Sudarshan Naidu Chilamakuri, Manasa N, Maharshi Thalla, Ravichandiran Velayutham, Youjin Lee, Sung Min Cho, Hyungil Jung, Subramanian Natesan","doi":"10.1021/acs.molpharmaceut.4c01115","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01115","url":null,"abstract":"<p><p>Obesity is a global metabolic health epidemic characterized by excessive lipid and fat accumulation, leading to severe conditions such as diabetes, cancer, and cardiovascular disease. Immediate attention and management of obesity-related health risks are most warranted. The imbalance between fat absorption, metabolic rate, and environmental and genetic factors is responsible for obesity. Treatment typically involves lifestyle modifications, pharmacotherapy, and surgery. While lifestyle changes are crucial, effective treatment often necessitates medication as a preferred adjunct strategy. However, medications commonly used, such as oral pharmacotherapy, often show side effects due to systemic exposure and, thus, may not effectively target the intended areas, leading to drug loss. On the other hand, transdermal administration of drugs with microneedle (MN)-based technologies, a painless drug delivery approach with patient compliance, is gaining interest as an alternative obesity treatment, as it directly targets adipose tissue via local delivery, minimizing system exposure and dose reduction. This Review addresses the pathophysiology of obesity, current treatment strategies, challenges in the treatment of obesity using conventional formulations, the importance of the use of nano-based medications through transdermal delivery, and the use of MNs as a promising platform for the effective delivery of nanoparticle-based anti-obesity medications. The potential of combining MNs with stimuli-responsive and non-responsive adjuvant therapies to enhance treatment efficacy and patient outcomes is explored. In addition, the limitations and future perspectives related to the use of MNs for obesity are addressed to highlight the transformative potential of this technology for obesity management. MNs hold promise in precisely delivering anti-obesity drugs while requiring lower dosages and minimizing side effects compared to conventional oral or injectable therapies and ultimately improving the quality of life for individuals struggling with obesity and its associated comorbidities.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750285","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":"Investigation of a Palbociclib and Naringin Co-Amorphous System to Ameliorate Anticancer Potential: Insights on <i>In Silico Modeling,</i> Physicochemical Characterization, <i>Ex Vivo</i> Permeation, and <i>In Vitro</i> Efficacy.","authors":"Tanmoy Kanp, Anish Dhuri, Mayur Aalhate, Bharath Manoharan, Khushi Rode, Sharon Munagalasetty, Akella V S Sarma, Prasad Kshirsagar, Nagula Shankaraiah, Vasundhara Bhandari, Bhagwati Sharma, Pankaj Kumar Singh","doi":"10.1021/acs.molpharmaceut.4c01224","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01224","url":null,"abstract":"<p><p>Palbociclib (PCB), categorized as a BCS class II drug, is characterized by low aqueous solubility. The drug's limited aqueous solubility and poor dissolution rate pose significant challenges, potentially affecting its absorption and overall therapeutic efficacy. Co-amorphous (CAM) systems have been extensively investigated as a potential solution to overcome the issue of poor water solubility in numerous active pharmaceutical ingredients. This research study hypothesized that the coamorphization process involving the compounds PCB and naringin (NG) would lead to an increase in the aqueous solubility of PCB. Additionally, it was proposed that this process would also enhance the anticancer impact of PCB since NG is recognized for its pharmacological impact on breast cancer cells. <i>In silico</i> studies, it was revealed that PCB could interact with NG via hydrogen bonding. Furthermore, the prepared CAM (PCB-NG-CAM) system using PCB and NG was characterized by PXRD, DSC, FTIR, Raman spectroscopy, solid-state ¹³C nuclear magnetic resonance, and SEM. PCB-NG-CAM exhibited a significant increase in solubility, dissolution rate, and intestinal permeation compared to crystalline PCB. Furthermore, PCB-NG-CAM exhibited excellent physical stability at 40 °C/75% RH for up to 3 months. In addition, PCB-NG-CAM showed superior <i>in vitro</i> efficacy on MDA-MB-231 triple-negative breast cancer cell lines. PCB-NG-CAM resulted in a 2.24 times higher apoptosis rate and a 1.6 times greater ROS production than free PCB. Additionally, the inhibitory effect on cell migration and alterations in MMP was more pronounced in cells treated with PCB-NG-CAM. Therefore, this study indicated that PCB-NG-CAM has the potential to significantly improve the oral administration, solubility, and therapeutic efficacy of PCB.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750283","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":"Metal-Polyphenol Self-Assembled Nanophotothermal Agent for Precise Mitochondrial Targeted Photothermal Therapy.","authors":"Jun Zhou, Wensong Wang, Yong Li, Qianqian Liu, Fan Liu, Qiao Zhang, Yunfei Zhang, Can Jiang, Si Chen, Fei-Peng Du, Jinxuan Fan","doi":"10.1021/acs.molpharmaceut.4c01474","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01474","url":null,"abstract":"<p><p>Nanocarriers have been extensively utilized to improve the stability of photothermal agents in vivo, enhance delivery efficiency, and reduce drug side effects. However, challenges, such as the low safety of carrier materials, insufficient loading of therapeutic agents, and complex preparation procedures, still persist. In this study, the photothermal agent IR780 was encapsulated in network TA-Fe³⁺ (TF) which was self-assembled by tannic acid (TA) and Fe³⁺ to synthesize an acid-responsive multifunctional nanophotothermal agent TF@IR780 (TR). In the slightly acidic tumor microenvironment (TME), network shell TF is degraded, and the internal photothermal agent IR780 is exposed. On the one hand, the TF network can improve the solubility and stability of photothermal agent IR780 in vivo and significantly increase the uptake efficiency in tumor cells. On the other hand, Fe³⁺ exhibits magnetic resonance imaging (MRI) functionality, which combined with the fluorescence imaging of IR780 endows TR with multimodal imaging capabilities. In addition, TR is easy to release photosensitizers through acid response in the low pH environment of TME, and achieves precise damage to mitochondria through mitochondrial anchoring and light regulation. This overcomes the drawbacks of traditional tumor treatment methods, such as poor specificity, and demonstrates efficient and controllable antitumor activity.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735548","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":"Construction of Bispecific T-Cell Engager Radiotracer and Its Micro-PET Evaluation in Pancreatic Cancer.","authors":"Dan Wen, Qi Wang, Jin Ding, Zilei Wang, Shiyu Lin, Hao Zhang, Xiaohong Huang, Xiaokun Ma, Xingguo Hou, Suping Li, Hua Zhu, Zhi Yang","doi":"10.1021/acs.molpharmaceut.5c00072","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00072","url":null,"abstract":"<p><p>Mucin 17 (MUC17), a transmembrane mucin, is overexpressed in pancreatic cancer and is associated with tumor proliferation and metastasis. CD3 is an indispensable molecule on the surface of T lymphocytes, which is associated with T cell activation and participates in immune responses. Here, we developed a bispecific T-cell engager radiotracer, ⁸⁹Zr-M17C3, targeting MUC17 and CD3, to enable noninvasive PET imaging of both tumor cells and T-cell infiltration in pancreatic cancer. ⁸⁹Zr-M17C3 was synthesized by conjugating AMG199 with zirconium-89 and verified for its radiochemical purity and in vitro stability. The ⁸⁹Zr-M17C3 probe demonstrated excellent radiochemical purity (>99%) and stability (maintained ≥99% over 120 h). Cellular uptake assays and binding affinity studies were conducted to evaluate the probe's specificity for MUC17 and CD3. Micro-PET/CT imaging and biodistribution studies were performed in MUC17-expressing nude mice and CD3 humanized mice to assess probe uptake in tumors and T-cell-infiltrated tissues. In MUC17-expressing AsPC-1 tumors, probe uptake was significantly higher than in MUC17-negative PANC-1 tumors (SUVmax: 2.26 ± 0.18 vs 1.13 ± 0.14, <i>P</i> < 0.001) and was confirmed to be MUC17-dependent through blocking studies. In CD3 humanized mice, the probe was able to visualize both T-cell infiltration and MUC17-positive tumors, with peak uptake in AsPC-1 tumors (SUVmax: 2.35 ± 0.46) and spleen (SUVmax: 2.19 ± 0.40) at 216 h. Immunohistochemical analysis confirmed the spatial correlation between MUC17 expression and CD3-positive T-cell infiltration in AsPC-1 tumors but not in PANC-1 tumors. In summary, the ⁸⁹Zr-M17C3 radiotracer exhibited high affinity for MUC17 and CD3 and successfully differentiated MUC17-positive tumors from MUC17-negative tumors while simultaneously providing insight into the T-cell distribution. This study highlights the potential of ⁸⁹Zr-M17C3 as a versatile imaging tool to support patient stratification and therapeutic monitoring in tumor-targeted immunotherapy, particularly for bispecific T-cell engager-based approaches such as AMG199.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727092","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 In Vitro Characterization of Milk-Derived Extracellular Vesicle-Mithramycin Formulations for Potential Glioma Therapy.","authors":"Sreekanth Patnam, Anula Divyash Singh, Mohammad Sadik Ali, Basant Kumar Thakur, Aravind Kumar Rengan, Sasidhar Venkata Manda","doi":"10.1021/acs.molpharmaceut.4c01189","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01189","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a highly aggressive brain tumor with resistance to conventional therapies. Mithramycin (Mit-A), a potent antitumor agent, has shown promise in several tumor types including, GBM. However, its clinical application is limited by toxicity. To address this, we explored the use of milk-derived extracellular vesicles (mEVs) as a delivery system to enhance the therapeutic efficacy of Mit-A. In this study, mEVs were isolated using a 3000 PEG precipitation method and confirmed their size, morphology, and stability through dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The isolated vesicles with a size of 125.6 ± 2.78 nm, a polydispersity index (PDI) of 0.083 ± 0.02, and a ζ-potential of 15 ± 0.57 mV. The presence of typical EV markers such as TSG101, HSP70, and CD63 confirmed their purity. Encapsulation of Mit-A within mEVs led to a slight increase in size to 131.8 ± 6.9 nm, a PDI of 0.081 ± 0.006, and a decrease in ζ-potential to -17 ± 2.0 mV, with an encapsulation efficiency of 58% by the freeze-thaw method. The in vitro transepithelial transport assay revealed that mEV(Mit-A) transported Mit-A more effectively than free Mit-A. The mEV(Mit-A) formulation demonstrated excellent stability in simulated salivary and gastrointestinal fluids, with a sustained release of Mit-A observed over 24 h in vitro in PBS (pH 6.8). Furthermore, mEV(Mit-A) formulations significantly inhibited glioma cell growth, and migration, and induced apoptosis, showing a 2-fold lower IC50 than free Mit-A, indicating superior efficacy. These findings suggest that mEVs represent a promising delivery vehicle for Mit-A, enhancing its potential as an effective treatment for glioblastoma.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727093","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 Insight into Lipid Nanoparticle Assembly from NMR Spectroscopy and Molecular Dynamics Simulation.","authors":"Mingyue Li, Ryan Schroder, Umut Ozuguzel, Tyler M Corts, Yong Liu, Yuejie Zhao, Wei Xu, Jing Ling, Allen C Templeton, Bodhisattwa Chaudhuri, Marian Gindy, Angela Wagner, Yongchao Su","doi":"10.1021/acs.molpharmaceut.4c01437","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01437","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) have emerged as the premier drug delivery system for oligonucleotide vaccines and therapeutics in recent years. Despite their prosperous advancement in research and clinical applications, there is a significant lack of mechanistic understanding of the assembly of lipid particles at the molecular level. In our study, we utilized a combination of solution and solid-state NMR, together with molecular dynamics simulations, to elucidate local structures and interactions of chemical components across multiple motional regimes. Our results comprehensively evaluated the impact of formulation components and engineering process factors on the particle formation and identified the interplay of phospholipids (DSPC), poly(ethylene glycol) (PEG) lipid conjugates, and cholesterol in governing the particle size and lipid dynamics from a structural perspective, using static ³¹P NMR techniques. These studies provide novel insights into the impact of particle engineering on the molecular properties of the LNP envelope membrane. Additionally, molecular interactions and compositional distribution play a critical role in particle engineering and the consequent stability and potency. In this study, we have identified intermolecular contacts among the lipid components using one-dimensional ¹H-¹³C cross-polarization magic angle spinning experiments, ¹H relaxation measurements, and two-dimensional ¹H-¹H correlation methods, providing a structural basis for the lipid assembly. Interestingly, the cationic and ionizable lipids, conventionally regarded as stabilizing agents primarily located within the core of LNPs, were found to interact with PEG lipids and coexist in the outer layer of the particles. We suggest that LNPs examined here are comprised of an outer layer rich in lipid components surrounding a core region. Our high-resolution findings offer insightful structural and dynamic details pertaining to the individual chemical components in the lipid particles and their interactions influence lipid complex structure and stability in particle engineering.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707773","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":"Engineered Turmeric-Derived Nanovesicles for Ulcerative Colitis Therapy by Attenuating Oxidative Stress and Alleviating Inflammation.","authors":"Guihong Lu, Shanming Lu, Haibing Dai, Fan Zhang, Xiaotian Wang, Weiqun Li, Lin Mei, Hui Tan","doi":"10.1021/acs.molpharmaceut.4c01328","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01328","url":null,"abstract":"<p><p>Inflammation and oxidative stress are important features of traumatic ulcerative colitis (UC). Turmeric has been used as a dietary and functional ingredient for its potent anti-inflammatory effects in UC therapy. However, its practical effectiveness is hindered by limited reactive oxygen species (ROS) elimination properties. To address this, we constructed a unique treatment agent by growing cerium oxide (CeO₂) nanocrystals on the membranes of turmeric-derived nanovesicles (TNVs), named as TNV-Ce. The resulted TNV-Ce could suppress inflammation and exhibit exceptional ROS-scavenging activity, which was validated both in lipopolysaccharide-induced macrophages and dextran sulfate sodium salt-induced chronic colitis mouse model. Following oral administration, TNV-Ce significantly accumulated at inflamed sites, effectively eliminating ROS and inhibiting pro-inflammatory cytokines for synergistic action against UC.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707770","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}