Polymer-Functionalized Magnetic Nanoparticles for Targeted Quercetin Delivery: A Potential Strategy for Colon Cancer Treatment

<b>Background/Objectives</b>: Nanoparticle-based drug delivery systems improve pharmacokinetic aspects, including controlled release and drug targeting, increasing therapeutic efficacy, and reducing toxicity in conventional colon cancer treatment. The superparamagnetism of magnetic nanop...

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Main Authors: Júlia Borges de Macedo, Julia Narayana Schoroeder Bueno, Carla Cristine Kanunfre, José Ricardo de Arruda Miranda, Andris Figueiroa Bakuzis, Priscileila Colerato Ferrari
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/4/467
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author Júlia Borges de Macedo
Julia Narayana Schoroeder Bueno
Carla Cristine Kanunfre
José Ricardo de Arruda Miranda
Andris Figueiroa Bakuzis
Priscileila Colerato Ferrari
author_facet Júlia Borges de Macedo
Julia Narayana Schoroeder Bueno
Carla Cristine Kanunfre
José Ricardo de Arruda Miranda
Andris Figueiroa Bakuzis
Priscileila Colerato Ferrari
author_sort Júlia Borges de Macedo
collection DOAJ
description <b>Background/Objectives</b>: Nanoparticle-based drug delivery systems improve pharmacokinetic aspects, including controlled release and drug targeting, increasing therapeutic efficacy, and reducing toxicity in conventional colon cancer treatment. The superparamagnetism of magnetic nanoparticles (MNP) appears to be a potential alternative for magnetothermal therapy, inducing tumor cell death by an external magnetic field. Therefore, this study aimed to develop chitosan (CS) and folate-chitosan (FA-CS)-coated MNP to improve the stability and targeting of the system for quercetin (Q) delivery. <b>Methods</b>: After FA-CS synthesis and 3<sup>2</sup> factorial design, polymer-functionalized MNPs were produced for quercetin loading, characterized, and evaluated by drug dissolution and cytotoxicity assay. <b>Results</b>: The factorial design indicated the positive influence of CS on MNPs’ Zeta potential, followed by the CS–temperature interaction. Optimized formulations had hydrodynamic diameters of 122.32 ± 8.56 nm, Zeta potentials of +30.78 ± 0.8 mV, and loading efficiencies of 80.45% (MNP-CS-Q) and 54.4% (MNP-FA-CS-Q). The 24 h drug release was controlled in MNP-CS-Q (up to 6.4%) and MNP-FA-CS-Q (up to 7.7%) in a simulated tumor medium, with Fickian diffusion release mechanism correlated to the Korsmeyer–Peppas model (R > 0.99). The cytotoxicity assay in HCT-116 showed a higher (<i>p</i> < 0.001) dose-dependent antitumor effect of quercetin-loaded MNP compared to free drug, with IC50s of 1.46 (MNP-CS) and 1.30 µg·mL<sup>−1</sup> (MNP-FA-CS). <b>Conclusions</b>: Therefore, this study contributes to the development of biomedical nanotechnology and the magnetic debate by highlighting the antitumor potential of quercetin magnetic nanoparticles. The experimental design allows the discussion of critical manufacturing variables and the determination of optimal parameters for the formulations.
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spelling doaj-art-34a46e44cefa4e0ca5a742a45f58c60d2025-08-20T02:18:15ZengMDPI AGPharmaceutics1999-49232025-04-0117446710.3390/pharmaceutics17040467Polymer-Functionalized Magnetic Nanoparticles for Targeted Quercetin Delivery: A Potential Strategy for Colon Cancer TreatmentJúlia Borges de Macedo0Julia Narayana Schoroeder Bueno1Carla Cristine Kanunfre2José Ricardo de Arruda Miranda3Andris Figueiroa Bakuzis4Priscileila Colerato Ferrari5Department of Pharmaceutical Sciences, Ponta Grossa State University (UEPG), Ponta Grossa 84030-900, PR, BrazilDepartment of Pharmaceutical Sciences, Ponta Grossa State University (UEPG), Ponta Grossa 84030-900, PR, BrazilDepartment of General Biology, Ponta Grossa State University (UEPG), Ponta Grossa 84030-900, PR, BrazilDepartment of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-689, SP, BrazilInstitute of Physics, Federal University of Goiás, Goiânia 74690-900, GO, BrazilDepartment of Pharmaceutical Sciences, Ponta Grossa State University (UEPG), Ponta Grossa 84030-900, PR, Brazil<b>Background/Objectives</b>: Nanoparticle-based drug delivery systems improve pharmacokinetic aspects, including controlled release and drug targeting, increasing therapeutic efficacy, and reducing toxicity in conventional colon cancer treatment. The superparamagnetism of magnetic nanoparticles (MNP) appears to be a potential alternative for magnetothermal therapy, inducing tumor cell death by an external magnetic field. Therefore, this study aimed to develop chitosan (CS) and folate-chitosan (FA-CS)-coated MNP to improve the stability and targeting of the system for quercetin (Q) delivery. <b>Methods</b>: After FA-CS synthesis and 3<sup>2</sup> factorial design, polymer-functionalized MNPs were produced for quercetin loading, characterized, and evaluated by drug dissolution and cytotoxicity assay. <b>Results</b>: The factorial design indicated the positive influence of CS on MNPs’ Zeta potential, followed by the CS–temperature interaction. Optimized formulations had hydrodynamic diameters of 122.32 ± 8.56 nm, Zeta potentials of +30.78 ± 0.8 mV, and loading efficiencies of 80.45% (MNP-CS-Q) and 54.4% (MNP-FA-CS-Q). The 24 h drug release was controlled in MNP-CS-Q (up to 6.4%) and MNP-FA-CS-Q (up to 7.7%) in a simulated tumor medium, with Fickian diffusion release mechanism correlated to the Korsmeyer–Peppas model (R > 0.99). The cytotoxicity assay in HCT-116 showed a higher (<i>p</i> < 0.001) dose-dependent antitumor effect of quercetin-loaded MNP compared to free drug, with IC50s of 1.46 (MNP-CS) and 1.30 µg·mL<sup>−1</sup> (MNP-FA-CS). <b>Conclusions</b>: Therefore, this study contributes to the development of biomedical nanotechnology and the magnetic debate by highlighting the antitumor potential of quercetin magnetic nanoparticles. The experimental design allows the discussion of critical manufacturing variables and the determination of optimal parameters for the formulations.https://www.mdpi.com/1999-4923/17/4/467manganese ferritecancer therapysurface functionalizationdrug deliverymagnetic drug targetingfolate chitosan
spellingShingle Júlia Borges de Macedo
Julia Narayana Schoroeder Bueno
Carla Cristine Kanunfre
José Ricardo de Arruda Miranda
Andris Figueiroa Bakuzis
Priscileila Colerato Ferrari
Polymer-Functionalized Magnetic Nanoparticles for Targeted Quercetin Delivery: A Potential Strategy for Colon Cancer Treatment
Pharmaceutics
manganese ferrite
cancer therapy
surface functionalization
drug delivery
magnetic drug targeting
folate chitosan
title Polymer-Functionalized Magnetic Nanoparticles for Targeted Quercetin Delivery: A Potential Strategy for Colon Cancer Treatment
title_full Polymer-Functionalized Magnetic Nanoparticles for Targeted Quercetin Delivery: A Potential Strategy for Colon Cancer Treatment
title_fullStr Polymer-Functionalized Magnetic Nanoparticles for Targeted Quercetin Delivery: A Potential Strategy for Colon Cancer Treatment
title_full_unstemmed Polymer-Functionalized Magnetic Nanoparticles for Targeted Quercetin Delivery: A Potential Strategy for Colon Cancer Treatment
title_short Polymer-Functionalized Magnetic Nanoparticles for Targeted Quercetin Delivery: A Potential Strategy for Colon Cancer Treatment
title_sort polymer functionalized magnetic nanoparticles for targeted quercetin delivery a potential strategy for colon cancer treatment
topic manganese ferrite
cancer therapy
surface functionalization
drug delivery
magnetic drug targeting
folate chitosan
url https://www.mdpi.com/1999-4923/17/4/467
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