Md. Jashim Uddin*, Justin Han-Je Lo, Mukesh K. Gupta, Thomas A. Werfel, Abu Asaduzzaman, Connor G. Oltman, Eva F. Gbur, Mohammed T. Mohyuddin, Farhana Nazmin, Md. Saidur Rahman, Ahan Jashim, Brenda C. Crews, Philip J. Kingsley, Jamie E. Klendworth, Lawrence J. Marnett, Craig L. Duvall and Rebecca S. Cook*,
{"title":"聚合纳米颗粒可实现乳腺癌药物输送的靶向可视化","authors":"Md. Jashim Uddin*, Justin Han-Je Lo, Mukesh K. Gupta, Thomas A. Werfel, Abu Asaduzzaman, Connor G. Oltman, Eva F. Gbur, Mohammed T. Mohyuddin, Farhana Nazmin, Md. Saidur Rahman, Ahan Jashim, Brenda C. Crews, Philip J. Kingsley, Jamie E. Klendworth, Lawrence J. Marnett, Craig L. Duvall and Rebecca S. Cook*, ","doi":"10.1021/acs.molpharmaceut.4c0069510.1021/acs.molpharmaceut.4c00695","DOIUrl":null,"url":null,"abstract":"<p >We report the coencapsulation of fluorocoxib Q (FQ) and chemocoxib A (CA) in micellar nanoparticles (FQ-CA-NPs) of a new PPS<sub>135</sub>-<i>b</i>-POEGA<sub>17</sub> diblock polymer, which exhibited a hydrodynamic diameter of 109.2 ± 4.1 nm and a zeta potential (ζ) of −1.59 ± 0.3 mV. The uptake of FQ-CA-NPs by 4T1 mouse mammary cancer cells and intracellular cargo release were assessed by fluorescence microscopy that resulted in increased fluorescence in 4T1 cells compared to cells pretreated with celecoxib. The viability of primary human mammary epithelial cells (HMECs) or 4T1 mouse mammary carcinoma cells treated with FQ-CA-NPs were assessed, which showed decreased growth of 4T1 breast cancer cells but showed no effect on the growth of primary human mammary epithelial cells (HMECs). Intravenous dosing of FQ-CA-NPs in mice enabled ROS-induced cargo (FQ and CA) release and fluorescence activation of FQ and resulted in increased fluorescence in breast tumors compared to the tumors of animals pretreated with tempol or celecoxib, and minimum fluorescence was detected in the tumors of animals treated with nothing or empty-NPs. In addition, tumor tissues from treated animals were analyzed <i>ex vivo</i> by liquid chromatography–mass spectrometry (LC–MS)/MS, and identified increased levels of cargo delivery and retention in the tumor compared to tempol- or celecoxib-pretreated animal tumors. These <i>in vivo</i> and <i>ex vivo</i> results confirmed the targeted delivery of loaded NPs followed by ROS-mediated cargo release and fluorescence activation for targeted visualization of drug delivery in breast tumors and CA-induced therapeutic effect in an <i>in vivo</i> tumor growth inhibition assay and an <i>ex vivo</i> hematoxylin and eosin (H&E) staining of tumor tissues. Thus, coencapsulation of FQ and CA into polymeric micellar nanoparticles (FQ-CA-NPs) enabled their ROS-sensitive release followed by fluorescence activation and COX-2-dependent tumor targeting and retention in the visualization of CA delivery in solid breast tumors.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 5","pages":"2392–2401 2392–2401"},"PeriodicalIF":4.5000,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.molpharmaceut.4c00695","citationCount":"0","resultStr":"{\"title\":\"Polymeric Nanoparticles Enable Targeted Visualization of Drug Delivery in Breast Cancer\",\"authors\":\"Md. Jashim Uddin*, Justin Han-Je Lo, Mukesh K. Gupta, Thomas A. Werfel, Abu Asaduzzaman, Connor G. Oltman, Eva F. Gbur, Mohammed T. Mohyuddin, Farhana Nazmin, Md. Saidur Rahman, Ahan Jashim, Brenda C. Crews, Philip J. Kingsley, Jamie E. Klendworth, Lawrence J. Marnett, Craig L. Duvall and Rebecca S. Cook*, \",\"doi\":\"10.1021/acs.molpharmaceut.4c0069510.1021/acs.molpharmaceut.4c00695\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >We report the coencapsulation of fluorocoxib Q (FQ) and chemocoxib A (CA) in micellar nanoparticles (FQ-CA-NPs) of a new PPS<sub>135</sub>-<i>b</i>-POEGA<sub>17</sub> diblock polymer, which exhibited a hydrodynamic diameter of 109.2 ± 4.1 nm and a zeta potential (ζ) of −1.59 ± 0.3 mV. The uptake of FQ-CA-NPs by 4T1 mouse mammary cancer cells and intracellular cargo release were assessed by fluorescence microscopy that resulted in increased fluorescence in 4T1 cells compared to cells pretreated with celecoxib. The viability of primary human mammary epithelial cells (HMECs) or 4T1 mouse mammary carcinoma cells treated with FQ-CA-NPs were assessed, which showed decreased growth of 4T1 breast cancer cells but showed no effect on the growth of primary human mammary epithelial cells (HMECs). Intravenous dosing of FQ-CA-NPs in mice enabled ROS-induced cargo (FQ and CA) release and fluorescence activation of FQ and resulted in increased fluorescence in breast tumors compared to the tumors of animals pretreated with tempol or celecoxib, and minimum fluorescence was detected in the tumors of animals treated with nothing or empty-NPs. In addition, tumor tissues from treated animals were analyzed <i>ex vivo</i> by liquid chromatography–mass spectrometry (LC–MS)/MS, and identified increased levels of cargo delivery and retention in the tumor compared to tempol- or celecoxib-pretreated animal tumors. These <i>in vivo</i> and <i>ex vivo</i> results confirmed the targeted delivery of loaded NPs followed by ROS-mediated cargo release and fluorescence activation for targeted visualization of drug delivery in breast tumors and CA-induced therapeutic effect in an <i>in vivo</i> tumor growth inhibition assay and an <i>ex vivo</i> hematoxylin and eosin (H&E) staining of tumor tissues. 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Polymeric Nanoparticles Enable Targeted Visualization of Drug Delivery in Breast Cancer
We report the coencapsulation of fluorocoxib Q (FQ) and chemocoxib A (CA) in micellar nanoparticles (FQ-CA-NPs) of a new PPS135-b-POEGA17 diblock polymer, which exhibited a hydrodynamic diameter of 109.2 ± 4.1 nm and a zeta potential (ζ) of −1.59 ± 0.3 mV. The uptake of FQ-CA-NPs by 4T1 mouse mammary cancer cells and intracellular cargo release were assessed by fluorescence microscopy that resulted in increased fluorescence in 4T1 cells compared to cells pretreated with celecoxib. The viability of primary human mammary epithelial cells (HMECs) or 4T1 mouse mammary carcinoma cells treated with FQ-CA-NPs were assessed, which showed decreased growth of 4T1 breast cancer cells but showed no effect on the growth of primary human mammary epithelial cells (HMECs). Intravenous dosing of FQ-CA-NPs in mice enabled ROS-induced cargo (FQ and CA) release and fluorescence activation of FQ and resulted in increased fluorescence in breast tumors compared to the tumors of animals pretreated with tempol or celecoxib, and minimum fluorescence was detected in the tumors of animals treated with nothing or empty-NPs. In addition, tumor tissues from treated animals were analyzed ex vivo by liquid chromatography–mass spectrometry (LC–MS)/MS, and identified increased levels of cargo delivery and retention in the tumor compared to tempol- or celecoxib-pretreated animal tumors. These in vivo and ex vivo results confirmed the targeted delivery of loaded NPs followed by ROS-mediated cargo release and fluorescence activation for targeted visualization of drug delivery in breast tumors and CA-induced therapeutic effect in an in vivo tumor growth inhibition assay and an ex vivo hematoxylin and eosin (H&E) staining of tumor tissues. Thus, coencapsulation of FQ and CA into polymeric micellar nanoparticles (FQ-CA-NPs) enabled their ROS-sensitive release followed by fluorescence activation and COX-2-dependent tumor targeting and retention in the visualization of CA delivery in solid breast tumors.
期刊介绍：
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
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