Engineered PAM-SPION Nanoclusters for Enhanced Cancer Therapy: Integrating Magnetic Targeting with pH-Responsive Drug Release
Background: Nanomedicine approaches for cancer therapy face significant challenges, including a poor tumor accumulation, limited therapeutic efficacy, and systemic toxicity. We hypothesized that controlling the clustering of poly(acrylic acid-co-maleic acid) (PAM)-coated superparamagnetic iron oxide...
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2025-06-01
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| author | Dimitra Tzavara Konstantina Papadia Argiris Kolokithas-Ntoukas Sophia G. Antimisiaris Athanasios Skouras |
| author_facet | Dimitra Tzavara Konstantina Papadia Argiris Kolokithas-Ntoukas Sophia G. Antimisiaris Athanasios Skouras |
| author_sort | Dimitra Tzavara |
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| description | Background: Nanomedicine approaches for cancer therapy face significant challenges, including a poor tumor accumulation, limited therapeutic efficacy, and systemic toxicity. We hypothesized that controlling the clustering of poly(acrylic acid-co-maleic acid) (PAM)-coated superparamagnetic iron oxide nanoparticles (SPIONs) would enhance their magnetic properties for improved targeting, while enabling a pH-responsive drug release in tumor microenvironments. Methods: PAM-stabilized SPION clusters were synthesized via arrested precipitation, characterized for physicochemical and magnetic properties, and evaluated for doxorubicin loading and pH-dependent release. A dual targeting approach combining antibody conjugation with magnetic guidance was assessed in cellular models, including a novel alternating magnetic field (AMF) pre-treatment protocol. Results: PAM-SPION clusters demonstrated controlled size distributions (60–100 nm), excellent colloidal stability, and enhanced magnetic properties, particularly for larger crystallites (13 nm). The formulations exhibited a pH-responsive drug release (8.5% at pH 7.4 vs. 14.3% at pH 6.5) and a significant enhancement of AMF-triggered release (17.5%). The dual targeting approach achieved an 8-fold increased cellular uptake compared to non-targeted formulations. Most notably, the novel AMF pre-treatment protocol demonstrated an 87% improved therapeutic efficacy compared to conventional post-treatment applications. Conclusions: The integration of targeting antibodies, magnetic guidance, and a pH-responsive PAM coating creates a versatile theranostic platform with significantly enhanced drug delivery capabilities. The unexpected synergistic effect of the AMF pre-treatment represents a promising new approach for improving the therapeutic efficacy of nanoparticle-based cancer treatments. |
| format | Article |
| id | doaj-art-8daf44ad38e24dcd83e05709c56ec778 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
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| series | Molecules |
| spelling | doaj-art-8daf44ad38e24dcd83e05709c56ec7782025-08-20T03:50:17ZengMDPI AGMolecules1420-30492025-06-013013278510.3390/molecules30132785Engineered PAM-SPION Nanoclusters for Enhanced Cancer Therapy: Integrating Magnetic Targeting with pH-Responsive Drug ReleaseDimitra Tzavara0Konstantina Papadia1Argiris Kolokithas-Ntoukas2Sophia G. Antimisiaris3Athanasios Skouras4Laboratory of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Rio Patras, GreeceLaboratory of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Rio Patras, GreeceLaboratory of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Rio Patras, GreeceLaboratory of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Rio Patras, GreeceLaboratory of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Rio Patras, GreeceBackground: Nanomedicine approaches for cancer therapy face significant challenges, including a poor tumor accumulation, limited therapeutic efficacy, and systemic toxicity. We hypothesized that controlling the clustering of poly(acrylic acid-co-maleic acid) (PAM)-coated superparamagnetic iron oxide nanoparticles (SPIONs) would enhance their magnetic properties for improved targeting, while enabling a pH-responsive drug release in tumor microenvironments. Methods: PAM-stabilized SPION clusters were synthesized via arrested precipitation, characterized for physicochemical and magnetic properties, and evaluated for doxorubicin loading and pH-dependent release. A dual targeting approach combining antibody conjugation with magnetic guidance was assessed in cellular models, including a novel alternating magnetic field (AMF) pre-treatment protocol. Results: PAM-SPION clusters demonstrated controlled size distributions (60–100 nm), excellent colloidal stability, and enhanced magnetic properties, particularly for larger crystallites (13 nm). The formulations exhibited a pH-responsive drug release (8.5% at pH 7.4 vs. 14.3% at pH 6.5) and a significant enhancement of AMF-triggered release (17.5%). The dual targeting approach achieved an 8-fold increased cellular uptake compared to non-targeted formulations. Most notably, the novel AMF pre-treatment protocol demonstrated an 87% improved therapeutic efficacy compared to conventional post-treatment applications. Conclusions: The integration of targeting antibodies, magnetic guidance, and a pH-responsive PAM coating creates a versatile theranostic platform with significantly enhanced drug delivery capabilities. The unexpected synergistic effect of the AMF pre-treatment represents a promising new approach for improving the therapeutic efficacy of nanoparticle-based cancer treatments.https://www.mdpi.com/1420-3049/30/13/2785superparamagnetic iron oxide nanoparticlesmagnetic targetingdrug deliverypH-responsivecancer therapyalternating magnetic field |
| spellingShingle | Dimitra Tzavara Konstantina Papadia Argiris Kolokithas-Ntoukas Sophia G. Antimisiaris Athanasios Skouras Engineered PAM-SPION Nanoclusters for Enhanced Cancer Therapy: Integrating Magnetic Targeting with pH-Responsive Drug Release Molecules superparamagnetic iron oxide nanoparticles magnetic targeting drug delivery pH-responsive cancer therapy alternating magnetic field |
| title | Engineered PAM-SPION Nanoclusters for Enhanced Cancer Therapy: Integrating Magnetic Targeting with pH-Responsive Drug Release |
| title_full | Engineered PAM-SPION Nanoclusters for Enhanced Cancer Therapy: Integrating Magnetic Targeting with pH-Responsive Drug Release |
| title_fullStr | Engineered PAM-SPION Nanoclusters for Enhanced Cancer Therapy: Integrating Magnetic Targeting with pH-Responsive Drug Release |
| title_full_unstemmed | Engineered PAM-SPION Nanoclusters for Enhanced Cancer Therapy: Integrating Magnetic Targeting with pH-Responsive Drug Release |
| title_short | Engineered PAM-SPION Nanoclusters for Enhanced Cancer Therapy: Integrating Magnetic Targeting with pH-Responsive Drug Release |
| title_sort | engineered pam spion nanoclusters for enhanced cancer therapy integrating magnetic targeting with ph responsive drug release |
| topic | superparamagnetic iron oxide nanoparticles magnetic targeting drug delivery pH-responsive cancer therapy alternating magnetic field |
| url | https://www.mdpi.com/1420-3049/30/13/2785 |
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