Platelet Membrane-Coated Poly (Lactic-Co-Glycolic Acid) Nanoparticles as a Targeting Drug Delivery System for Multidrug-Resistant Breast Cancer
Bomin Song,1,* Young-Guk Na,1,* Byung Jin Kim,1,* Minki Jin,1 Yo Han Song,1 Da-Eun Kim,1 Suyeon Hwang,1 Jong-Suep Baek,2 Hong-Ki Lee,3 Cheong-Weon Cho1 1College of Pharmacy, Chungnam National University, Daejeon, 31434, Republic of Korea; 2Department of Bio-Health...
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2025-07-01
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author | Song B Na YG Kim BJ Jin M Song YH Kim DE Hwang S Baek JS Lee HK Cho CW |
author_facet | Song B Na YG Kim BJ Jin M Song YH Kim DE Hwang S Baek JS Lee HK Cho CW |
author_sort | Song B |
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description | Bomin Song,1,* Young-Guk Na,1,* Byung Jin Kim,1,* Minki Jin,1 Yo Han Song,1 Da-Eun Kim,1 Suyeon Hwang,1 Jong-Suep Baek,2 Hong-Ki Lee,3 Cheong-Weon Cho1 1College of Pharmacy, Chungnam National University, Daejeon, 31434, Republic of Korea; 2Department of Bio-Health Convergence, Kangwon National University, Chuncheon, 24341, Republic of Korea; 3College of Veterinary Medicine, Chungbuk National University, Chungbuk, 28644, Republic of Korea*These authors contributed equally to this workCorrespondence: Cheong-Weon Cho, Email chocw@cnu.ac.kr Hong-Ki Lee, Email hongki.lee@cbnu.ac.krIntroduction: Paclitaxel (PTX), widely used chemotherapeutic agent, is limited by poor solubility, P-glycoprotein (P-gp) mediated efflux, and non-specific toxicity. To overcome these challenges, we developed a triple-functionalized nanocarrier system incorporating poly(lactide-co-glycolide) (PLGA)-based nanoparticles (PNs), D-α-tocopheryl polyethylene glycol succinate (TPGS) for P-gp inhibition, and platelet membrane (PM) coating for targeted tumor delivery.Methods: The PM-coated TPGS-modified PNs with PTX (PTPNs) was characterized by particle size analysis, transmission electron microscopy (TEM), and protein assay to confirm PM coating. In vitro drug release studies were conducted under acidic conditions mimicking the tumor microenvironment. Cellular assays were performed to evaluate cytotoxicity and drug efficacy in multidrug-resistant MCF-7/ADR cells. In vivo biodistribution and xenograft studies assessed tumor accumulation and therapeutic outcomes.Results: PTPNs exhibited a particle size of 221 ± 2 nm with a PDI of 0.090 ± 0.020 and a zeta potential of – 30.5 ± 0.3 mV, indicating a homogeneous particle distribution and successful PM coating. The optimal PM-to-PLGA weight ratio was determined to be 0.005, which ensured structural stability and uniform coating in physiological conditions. Sustained PTX release was observed in acidic conditions, mimicking the tumor microenvironment. Cellular assays showed a 17-fold reduction in PTX IC50 in MCF-7/ADR cells compared to free PTX, attributed to the synergistic effects of TPGS-mediated P-gp inhibition and PM–based tumor targeting. In vivo, PTPNs demonstrated enhanced tumor accumulation and significantly reduced tumor burden, with final tumor volume 2.6-fold lower than that of TPNs and 3.6-fold lower than that of the PTX commercial product (Taxol®)-treated group. Tumor necrosis factor-α (TNF-α) levels were also reduced, reflecting decreased tumor-promoting cytokine activity.Conclusion: The PTPNs enhanced PTX delivery by improving tumor specificity, overcoming multidrug resistance, and reducing systemic toxicity. These results suggested the potential of this biomimetic approach to advance cancer therapy.Keywords: paclitaxel, platelet membrane, Poly(lactide-co-glycolide), nanoparticles, multidrug resistance, cancer therapy |
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spelling | doaj-art-b0bab1e17c7b42db80b3b2a366ad73f02025-07-01T17:36:22ZengDove Medical PressInternational Journal of Nanomedicine1178-20132025-07-01Volume 20Issue 185298545104406Platelet Membrane-Coated Poly (Lactic-Co-Glycolic Acid) Nanoparticles as a Targeting Drug Delivery System for Multidrug-Resistant Breast CancerSong B0Na YG1Kim BJ2Jin MSong YHKim DE3Hwang SBaek JS4Lee HK5Cho CW6Department of PharmacyCollege of Pharmacy,Department of PharmacyCollege of PharmacyDepartment of Bio-Health ConvergenceCollege of Veterinary MedicineCollege of Pharmacy and Institute of Drug Research and DevelopmentBomin Song,1,* Young-Guk Na,1,* Byung Jin Kim,1,* Minki Jin,1 Yo Han Song,1 Da-Eun Kim,1 Suyeon Hwang,1 Jong-Suep Baek,2 Hong-Ki Lee,3 Cheong-Weon Cho1 1College of Pharmacy, Chungnam National University, Daejeon, 31434, Republic of Korea; 2Department of Bio-Health Convergence, Kangwon National University, Chuncheon, 24341, Republic of Korea; 3College of Veterinary Medicine, Chungbuk National University, Chungbuk, 28644, Republic of Korea*These authors contributed equally to this workCorrespondence: Cheong-Weon Cho, Email chocw@cnu.ac.kr Hong-Ki Lee, Email hongki.lee@cbnu.ac.krIntroduction: Paclitaxel (PTX), widely used chemotherapeutic agent, is limited by poor solubility, P-glycoprotein (P-gp) mediated efflux, and non-specific toxicity. To overcome these challenges, we developed a triple-functionalized nanocarrier system incorporating poly(lactide-co-glycolide) (PLGA)-based nanoparticles (PNs), D-α-tocopheryl polyethylene glycol succinate (TPGS) for P-gp inhibition, and platelet membrane (PM) coating for targeted tumor delivery.Methods: The PM-coated TPGS-modified PNs with PTX (PTPNs) was characterized by particle size analysis, transmission electron microscopy (TEM), and protein assay to confirm PM coating. In vitro drug release studies were conducted under acidic conditions mimicking the tumor microenvironment. Cellular assays were performed to evaluate cytotoxicity and drug efficacy in multidrug-resistant MCF-7/ADR cells. In vivo biodistribution and xenograft studies assessed tumor accumulation and therapeutic outcomes.Results: PTPNs exhibited a particle size of 221 ± 2 nm with a PDI of 0.090 ± 0.020 and a zeta potential of – 30.5 ± 0.3 mV, indicating a homogeneous particle distribution and successful PM coating. The optimal PM-to-PLGA weight ratio was determined to be 0.005, which ensured structural stability and uniform coating in physiological conditions. Sustained PTX release was observed in acidic conditions, mimicking the tumor microenvironment. Cellular assays showed a 17-fold reduction in PTX IC50 in MCF-7/ADR cells compared to free PTX, attributed to the synergistic effects of TPGS-mediated P-gp inhibition and PM–based tumor targeting. In vivo, PTPNs demonstrated enhanced tumor accumulation and significantly reduced tumor burden, with final tumor volume 2.6-fold lower than that of TPNs and 3.6-fold lower than that of the PTX commercial product (Taxol®)-treated group. Tumor necrosis factor-α (TNF-α) levels were also reduced, reflecting decreased tumor-promoting cytokine activity.Conclusion: The PTPNs enhanced PTX delivery by improving tumor specificity, overcoming multidrug resistance, and reducing systemic toxicity. These results suggested the potential of this biomimetic approach to advance cancer therapy.Keywords: paclitaxel, platelet membrane, Poly(lactide-co-glycolide), nanoparticles, multidrug resistance, cancer therapyhttps://www.dovepress.com/platelet-membrane-coated-poly-lactic-co-glycolic-acid-nanoparticles-as-peer-reviewed-fulltext-article-IJNPaclitaxelPlatelet membranePoly(lactide-co-glycolide) (PLGA)NanoparticlesMultidrug resistanceCancer therapy |
spellingShingle | Song B Na YG Kim BJ Jin M Song YH Kim DE Hwang S Baek JS Lee HK Cho CW Platelet Membrane-Coated Poly (Lactic-Co-Glycolic Acid) Nanoparticles as a Targeting Drug Delivery System for Multidrug-Resistant Breast Cancer International Journal of Nanomedicine Paclitaxel Platelet membrane Poly(lactide-co-glycolide) (PLGA) Nanoparticles Multidrug resistance Cancer therapy |
title | Platelet Membrane-Coated Poly (Lactic-Co-Glycolic Acid) Nanoparticles as a Targeting Drug Delivery System for Multidrug-Resistant Breast Cancer |
title_full | Platelet Membrane-Coated Poly (Lactic-Co-Glycolic Acid) Nanoparticles as a Targeting Drug Delivery System for Multidrug-Resistant Breast Cancer |
title_fullStr | Platelet Membrane-Coated Poly (Lactic-Co-Glycolic Acid) Nanoparticles as a Targeting Drug Delivery System for Multidrug-Resistant Breast Cancer |
title_full_unstemmed | Platelet Membrane-Coated Poly (Lactic-Co-Glycolic Acid) Nanoparticles as a Targeting Drug Delivery System for Multidrug-Resistant Breast Cancer |
title_short | Platelet Membrane-Coated Poly (Lactic-Co-Glycolic Acid) Nanoparticles as a Targeting Drug Delivery System for Multidrug-Resistant Breast Cancer |
title_sort | platelet membrane coated poly lactic co glycolic acid nanoparticles as a targeting drug delivery system for multidrug resistant breast cancer |
topic | Paclitaxel Platelet membrane Poly(lactide-co-glycolide) (PLGA) Nanoparticles Multidrug resistance Cancer therapy |
url | https://www.dovepress.com/platelet-membrane-coated-poly-lactic-co-glycolic-acid-nanoparticles-as-peer-reviewed-fulltext-article-IJN |
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