{"title":"配体密度vs机制洞察：配体共轭制剂治疗三阴性乳腺癌","authors":"Avijit Kumar Bakshi, Tanweer Haider, Dilip Panwar, Madhu Sharma, Pratiksha Tiwari, Nikhil Rai, Vandana Soni","doi":"10.1007/s11051-025-06443-7","DOIUrl":null,"url":null,"abstract":"<div><p>This study explores the targeted delivery of 5-fluorouracil (5-FU) using folic acid-functionalized chitosan nanoparticles (FA-CS NPs), optimizing folate receptor-mediated uptake in cancer cells. A key focus is the systematic modulation of folic acid (FA) Ligand density to enhance nanoparticle interaction with folate receptors, thereby improving therapeutic efficacy. FA was conjugated to chitosan via carbodiimide chemistry, confirmed by 1H NMR, and FA-CS NPs were formulated using ionic gelation. Characterization via SEM and DLS confirmed nanoparticles with controlled ligand density, influencing zeta potential and stability. In vitro studies assessed drug entrapment efficiency, release kinetics, and cytotoxic effects on MDA-MB-231 cells. Higher FA ligand densities correlated with increased cellular uptake and cytotoxicity due to enhanced receptor-mediated endocytosis. Cell cycle arrest and apoptosis assays further supported improved therapeutic performance. However, a threshold was identified beyond which increasing FA density did not significantly enhance cytotoxicity, indicating an optimal ligand concentration for maximum efficacy. These findings highlight the crucial role of ligand density in nanoparticle-based drug delivery, demonstrating that precise surface modifications can significantly impact therapeutic outcomes. FA-CS NPs offer a promising platform for targeted cancer treatment, potentially extending to other receptor-overexpressing malignancies. This study lays the groundwork for further research into ligand-engineered nanocarriers, aiming to refine targeted therapies for enhanced efficacy and reduced systemic toxicity.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":653,"journal":{"name":"Journal of Nanoparticle Research","volume":"27 10","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ligand density vs mechanistic insight: a ligand conjugated formulation for the treatment of triple-negative breast cancer\",\"authors\":\"Avijit Kumar Bakshi, Tanweer Haider, Dilip Panwar, Madhu Sharma, Pratiksha Tiwari, Nikhil Rai, Vandana Soni\",\"doi\":\"10.1007/s11051-025-06443-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>This study explores the targeted delivery of 5-fluorouracil (5-FU) using folic acid-functionalized chitosan nanoparticles (FA-CS NPs), optimizing folate receptor-mediated uptake in cancer cells. A key focus is the systematic modulation of folic acid (FA) Ligand density to enhance nanoparticle interaction with folate receptors, thereby improving therapeutic efficacy. FA was conjugated to chitosan via carbodiimide chemistry, confirmed by 1H NMR, and FA-CS NPs were formulated using ionic gelation. Characterization via SEM and DLS confirmed nanoparticles with controlled ligand density, influencing zeta potential and stability. In vitro studies assessed drug entrapment efficiency, release kinetics, and cytotoxic effects on MDA-MB-231 cells. Higher FA ligand densities correlated with increased cellular uptake and cytotoxicity due to enhanced receptor-mediated endocytosis. Cell cycle arrest and apoptosis assays further supported improved therapeutic performance. However, a threshold was identified beyond which increasing FA density did not significantly enhance cytotoxicity, indicating an optimal ligand concentration for maximum efficacy. These findings highlight the crucial role of ligand density in nanoparticle-based drug delivery, demonstrating that precise surface modifications can significantly impact therapeutic outcomes. FA-CS NPs offer a promising platform for targeted cancer treatment, potentially extending to other receptor-overexpressing malignancies. This study lays the groundwork for further research into ligand-engineered nanocarriers, aiming to refine targeted therapies for enhanced efficacy and reduced systemic toxicity.</p><h3>Graphical Abstract</h3>\\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":653,\"journal\":{\"name\":\"Journal of Nanoparticle Research\",\"volume\":\"27 10\",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Nanoparticle Research\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s11051-025-06443-7\",\"RegionNum\":4,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nanoparticle Research","FirstCategoryId":"88","ListUrlMain":"https://link.springer.com/article/10.1007/s11051-025-06443-7","RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Ligand density vs mechanistic insight: a ligand conjugated formulation for the treatment of triple-negative breast cancer
This study explores the targeted delivery of 5-fluorouracil (5-FU) using folic acid-functionalized chitosan nanoparticles (FA-CS NPs), optimizing folate receptor-mediated uptake in cancer cells. A key focus is the systematic modulation of folic acid (FA) Ligand density to enhance nanoparticle interaction with folate receptors, thereby improving therapeutic efficacy. FA was conjugated to chitosan via carbodiimide chemistry, confirmed by 1H NMR, and FA-CS NPs were formulated using ionic gelation. Characterization via SEM and DLS confirmed nanoparticles with controlled ligand density, influencing zeta potential and stability. In vitro studies assessed drug entrapment efficiency, release kinetics, and cytotoxic effects on MDA-MB-231 cells. Higher FA ligand densities correlated with increased cellular uptake and cytotoxicity due to enhanced receptor-mediated endocytosis. Cell cycle arrest and apoptosis assays further supported improved therapeutic performance. However, a threshold was identified beyond which increasing FA density did not significantly enhance cytotoxicity, indicating an optimal ligand concentration for maximum efficacy. These findings highlight the crucial role of ligand density in nanoparticle-based drug delivery, demonstrating that precise surface modifications can significantly impact therapeutic outcomes. FA-CS NPs offer a promising platform for targeted cancer treatment, potentially extending to other receptor-overexpressing malignancies. This study lays the groundwork for further research into ligand-engineered nanocarriers, aiming to refine targeted therapies for enhanced efficacy and reduced systemic toxicity.
期刊介绍：
The objective of the Journal of Nanoparticle Research is to disseminate knowledge of the physical, chemical and biological phenomena and processes in structures that have at least one lengthscale ranging from molecular to approximately 100 nm (or submicron in some situations), and exhibit improved and novel properties that are a direct result of their small size.
Nanoparticle research is a key component of nanoscience, nanoengineering and nanotechnology.
The focus of the Journal is on the specific concepts, properties, phenomena, and processes related to particles, tubes, layers, macromolecules, clusters and other finite structures of the nanoscale size range. Synthesis, assembly, transport, reactivity, and stability of such structures are considered. Development of in-situ and ex-situ instrumentation for characterization of nanoparticles and their interfaces should be based on new principles for probing properties and phenomena not well understood at the nanometer scale. Modeling and simulation may include atom-based quantum mechanics; molecular dynamics; single-particle, multi-body and continuum based models; fractals; other methods suitable for modeling particle synthesis, assembling and interaction processes. Realization and application of systems, structures and devices with novel functions obtained via precursor nanoparticles is emphasized. Approaches may include gas-, liquid-, solid-, and vacuum-based processes, size reduction, chemical- and bio-self assembly. Contributions include utilization of nanoparticle systems for enhancing a phenomenon or process and particle assembling into hierarchical structures, as well as formulation and the administration of drugs. Synergistic approaches originating from different disciplines and technologies, and interaction between the research providers and users in this field, are encouraged.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
