One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor Treatment
Jin Cao,* Mingxue Zheng,* Zhenyan Sun, Zhiye Li, Xueyong Qi, Song Shen School of Pharmacy, Jiangsu University, Zhenjiang, 212013, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Song Shen; Xueyong Qi, School of Pharmacy, Jiang...
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Dove Medical Press
2022-06-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/one-step-fabrication-of-multifunctional-plga-hmme-dtxmno2-nanoparticle-peer-reviewed-fulltext-article-IJN |
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| author | Cao J Zheng M Sun Z Li Z Qi X Shen S |
| author_facet | Cao J Zheng M Sun Z Li Z Qi X Shen S |
| author_sort | Cao J |
| collection | DOAJ |
| description | Jin Cao,* Mingxue Zheng,* Zhenyan Sun, Zhiye Li, Xueyong Qi, Song Shen School of Pharmacy, Jiangsu University, Zhenjiang, 212013, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Song Shen; Xueyong Qi, School of Pharmacy, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People’s Republic of China, Tel +86-0511-88795939, Email jsda.shensong@163.com; qixyemail@163.comBackground: Sonodynamic therapy (SDT) and its synergistic cancer therapy derivatives, such as combined chemotherapy-SDT (chemo-SDT), are promising approaches for tumor treatment. However, the main drawbacks restricting their applications are hypoxia in tumors and the reducing microenvironment or high glutathione (GSH) levels.Methods: In this study, a hybrid metal MnO2 was deposited onto nanoparticles fabricated using poly(lactic-co-glycolic acid) (PLGA), carrying docetaxel (DTX) and the sonosensitizer hematoporphyrin monomethyl ether (HMME) (PHD@MnO2) via a one-step flash nanoprecipitation (FNP) method. Characterization and in vitro and in vivo experiments were conducted to explore the chemo-SDT effect of PHD@MnO2 and evaluate the synergetic antitumor treatment of this nanosystem.Results: When low-power ultrasound is applied, the acquired PHD@MnO2, whether in solution or in MCF-7 cells, generated ROS more efficiently than other groups without MnO2 or those treated via monotherapy. Specifically, GSH-depletion was observed when MnO2 was introduced into the system. PHD@MnO2 presented good biocompatibility and biosafety in vitro and in vivo. These results indicated that the PHD@MnO2 nanoparticles overcame hypoxia in tumor tissue and suppressed the expression of hypoxia-inducible factor 1 alpha (HIF-1α), achieving enhanced chemo-SDT.Conclusion: This study provides a paradigm that rationally engineered multifunctional metal-hybrid nanoparticles can serve as an effective platform for augmenting the antitumor therapeutic efficiency of chemo-SDT.Keywords: sonodynamic therapy, flash nanoprecipitation, manganese dioxide, PLGA nanoparticle, GSH-depletion, hypoxia |
| first_indexed | 2024-04-13T12:13:15Z |
| format | Article |
| id | doaj.art-db06d50d720a4437bc8c5158b7fa188f |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-04-13T12:13:15Z |
| publishDate | 2022-06-01 |
| publisher | Dove Medical Press |
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| series | International Journal of Nanomedicine |
| spelling | doaj.art-db06d50d720a4437bc8c5158b7fa188f2022-12-22T02:47:26ZengDove Medical PressInternational Journal of Nanomedicine1178-20132022-06-01Volume 172577259175799One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor TreatmentCao JZheng MSun ZLi ZQi XShen SJin Cao,* Mingxue Zheng,* Zhenyan Sun, Zhiye Li, Xueyong Qi, Song Shen School of Pharmacy, Jiangsu University, Zhenjiang, 212013, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Song Shen; Xueyong Qi, School of Pharmacy, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People’s Republic of China, Tel +86-0511-88795939, Email jsda.shensong@163.com; qixyemail@163.comBackground: Sonodynamic therapy (SDT) and its synergistic cancer therapy derivatives, such as combined chemotherapy-SDT (chemo-SDT), are promising approaches for tumor treatment. However, the main drawbacks restricting their applications are hypoxia in tumors and the reducing microenvironment or high glutathione (GSH) levels.Methods: In this study, a hybrid metal MnO2 was deposited onto nanoparticles fabricated using poly(lactic-co-glycolic acid) (PLGA), carrying docetaxel (DTX) and the sonosensitizer hematoporphyrin monomethyl ether (HMME) (PHD@MnO2) via a one-step flash nanoprecipitation (FNP) method. Characterization and in vitro and in vivo experiments were conducted to explore the chemo-SDT effect of PHD@MnO2 and evaluate the synergetic antitumor treatment of this nanosystem.Results: When low-power ultrasound is applied, the acquired PHD@MnO2, whether in solution or in MCF-7 cells, generated ROS more efficiently than other groups without MnO2 or those treated via monotherapy. Specifically, GSH-depletion was observed when MnO2 was introduced into the system. PHD@MnO2 presented good biocompatibility and biosafety in vitro and in vivo. These results indicated that the PHD@MnO2 nanoparticles overcame hypoxia in tumor tissue and suppressed the expression of hypoxia-inducible factor 1 alpha (HIF-1α), achieving enhanced chemo-SDT.Conclusion: This study provides a paradigm that rationally engineered multifunctional metal-hybrid nanoparticles can serve as an effective platform for augmenting the antitumor therapeutic efficiency of chemo-SDT.Keywords: sonodynamic therapy, flash nanoprecipitation, manganese dioxide, PLGA nanoparticle, GSH-depletion, hypoxiahttps://www.dovepress.com/one-step-fabrication-of-multifunctional-plga-hmme-dtxmno2-nanoparticle-peer-reviewed-fulltext-article-IJNsonodynamic therapyflash nanoprecipitationmanganese dioxideplga nanoparticlegsh-depletionhypoxia |
| spellingShingle | Cao J Zheng M Sun Z Li Z Qi X Shen S One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor Treatment International Journal of Nanomedicine sonodynamic therapy flash nanoprecipitation manganese dioxide plga nanoparticle gsh-depletion hypoxia |
| title | One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor Treatment |
| title_full | One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor Treatment |
| title_fullStr | One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor Treatment |
| title_full_unstemmed | One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor Treatment |
| title_short | One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor Treatment |
| title_sort | one step fabrication of multifunctional plga hmme dtx mno2 nanoparticles for enhanced chemo sonodynamic antitumor treatment |
| topic | sonodynamic therapy flash nanoprecipitation manganese dioxide plga nanoparticle gsh-depletion hypoxia |
| url | https://www.dovepress.com/one-step-fabrication-of-multifunctional-plga-hmme-dtxmno2-nanoparticle-peer-reviewed-fulltext-article-IJN |
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