Loading...
Polymeric nanoparticles enable targeted visualization of drug delivery in breast cancer
Uddin, Md. Jashim Lo, Justin Han-Je Gupta, Mukesh K. Werfel, Thomas A. Asaduzzaman, Abu Oltman, Connor G. Gbur, Eva F. Mohyuddin, Mohammed T. Nazmin, Farhana Rahman, Md. Saidur
Uddin, Md. Jashim
Lo, Justin Han-Je
Gupta, Mukesh K.
Werfel, Thomas A.
Asaduzzaman, Abu
Oltman, Connor G.
Gbur, Eva F.
Mohyuddin, Mohammed T.
Nazmin, Farhana
Rahman, Md. Saidur
Citations
Altmetric:
Authors
Other Names
Location
Time Period
Advisors
Original Date
Digitization Date
Issue Date
2025-04-21
Type
Article
Genre
Keywords
Chemocoxib A,Drug delivery,Fluorocoxib Q,Micellar nanoparticles,Tumor imaging
Subjects (LCSH)
Citation
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
Molecular Pharmaceutics 2025 22 (5), 2392-2401
DOI: 10.1021/acs.molpharmaceut.4c00695
Abstract
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. © 2025 The Authors. Published by American Chemical Society.
Table of Contents
Description
This is an open access article under the CC BY license.
Publisher
American Chemical Society
Journal
Molecular Pharmaceutics
Book Title
Series
Digital Collection
Finding Aid URL
Use and Reproduction
Archival Collection
PubMed ID
ISSN
15438384