Platelet membrane biomimetic bufalin-loaded hollow MnO2 nanoparticles for MRI-guided chemo-chemodynamic combined therapy of cancer

Haijun Wang, David H. Bremner, Kunhua Wu, Xiarong Gong, Qing Fan, Xiaotian Xie, Hongmei Zhang, Junzi Wu, Li-Min Zhu*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

In this study, platelet membrane (PLTM) biomimetic hollow MnO2 nanoparticles were prepared and these were investigated for delivery of bufalin. Additionally, these nanoparticles, in response to the tumor microenvironment, showed rapid drug release and generated the hydroxyl radicals (HO•) by the Fenton reaction between Mn2+ and endogenous H2O2 for use in MRI-guided anti-tumor activity. Firstly, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were used to reduce KMnO4 to HMnO2 nanoparticles followed by acetone etching. After bufalin loading, these NPs were biomimetically cloaked with PLTM to form PLTM-HMnO2@Bu NPs. In vitro release profiles showed that the NPs responded to acid pH and glutathione (GSH) to induce decomposition of MnO2, resulting in rapid release of bufalin and yielding the MRI contrast agent Mn2+. In vivo MRI studies revealed an obvious T1 contrast enhancement at the tumor site because of a combination of the EPR and active targeting effects. The PLTM-HMnO2 NPs led to effective inhibition of tumor growth, attributing to Fenton-like Mn2+ conversion of endogenous H2O2 in the tumor to highly toxic HO• and this anti-tumor efficacy was enhanced when combined with chemotherapy. These results indicate that the PLTM biomimetic HMnO2 nanoparticles are promising drug delivery systems for MRI-monitoring and enhanced targeted treatment of tumors.
Original languageEnglish
Article number122848
Number of pages15
JournalChemical Engineering Journal
Volume382
Early online date16 Sep 2019
DOIs
Publication statusE-pub ahead of print - 16 Sep 2019

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Biomimetics
Platelets
tumor
Magnetic resonance imaging
Tumors
cancer
Nanoparticles
membrane
Membranes
hydroxyl radical
Hydroxyl Radical
drug
chemotherapy
Chemotherapy
etching
Acids
Poisons
acid
electron spin resonance
Acetone

Cite this

Wang, Haijun ; Bremner, David H. ; Wu, Kunhua ; Gong, Xiarong ; Fan, Qing ; Xie, Xiaotian ; Zhang, Hongmei ; Wu, Junzi ; Zhu, Li-Min. / Platelet membrane biomimetic bufalin-loaded hollow MnO2 nanoparticles for MRI-guided chemo-chemodynamic combined therapy of cancer. In: Chemical Engineering Journal. 2020 ; Vol. 382.
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abstract = "In this study, platelet membrane (PLTM) biomimetic hollow MnO2 nanoparticles were prepared and these were investigated for delivery of bufalin. Additionally, these nanoparticles, in response to the tumor microenvironment, showed rapid drug release and generated the hydroxyl radicals (HO•) by the Fenton reaction between Mn2+ and endogenous H2O2 for use in MRI-guided anti-tumor activity. Firstly, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were used to reduce KMnO4 to HMnO2 nanoparticles followed by acetone etching. After bufalin loading, these NPs were biomimetically cloaked with PLTM to form PLTM-HMnO2@Bu NPs. In vitro release profiles showed that the NPs responded to acid pH and glutathione (GSH) to induce decomposition of MnO2, resulting in rapid release of bufalin and yielding the MRI contrast agent Mn2+. In vivo MRI studies revealed an obvious T1 contrast enhancement at the tumor site because of a combination of the EPR and active targeting effects. The PLTM-HMnO2 NPs led to effective inhibition of tumor growth, attributing to Fenton-like Mn2+ conversion of endogenous H2O2 in the tumor to highly toxic HO• and this anti-tumor efficacy was enhanced when combined with chemotherapy. These results indicate that the PLTM biomimetic HMnO2 nanoparticles are promising drug delivery systems for MRI-monitoring and enhanced targeted treatment of tumors.",
author = "Haijun Wang and Bremner, {David H.} and Kunhua Wu and Xiarong Gong and Qing Fan and Xiaotian Xie and Hongmei Zhang and Junzi Wu and Li-Min Zhu",
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Platelet membrane biomimetic bufalin-loaded hollow MnO2 nanoparticles for MRI-guided chemo-chemodynamic combined therapy of cancer. / Wang, Haijun; Bremner, David H.; Wu, Kunhua; Gong, Xiarong; Fan, Qing; Xie, Xiaotian; Zhang, Hongmei; Wu, Junzi; Zhu, Li-Min.

In: Chemical Engineering Journal, Vol. 382, 122848, 15.02.2020.

Research output: Contribution to journalArticle

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T1 - Platelet membrane biomimetic bufalin-loaded hollow MnO2 nanoparticles for MRI-guided chemo-chemodynamic combined therapy of cancer

AU - Wang, Haijun

AU - Bremner, David H.

AU - Wu, Kunhua

AU - Gong, Xiarong

AU - Fan, Qing

AU - Xie, Xiaotian

AU - Zhang, Hongmei

AU - Wu, Junzi

AU - Zhu, Li-Min

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Y1 - 2019/9/16

N2 - In this study, platelet membrane (PLTM) biomimetic hollow MnO2 nanoparticles were prepared and these were investigated for delivery of bufalin. Additionally, these nanoparticles, in response to the tumor microenvironment, showed rapid drug release and generated the hydroxyl radicals (HO•) by the Fenton reaction between Mn2+ and endogenous H2O2 for use in MRI-guided anti-tumor activity. Firstly, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were used to reduce KMnO4 to HMnO2 nanoparticles followed by acetone etching. After bufalin loading, these NPs were biomimetically cloaked with PLTM to form PLTM-HMnO2@Bu NPs. In vitro release profiles showed that the NPs responded to acid pH and glutathione (GSH) to induce decomposition of MnO2, resulting in rapid release of bufalin and yielding the MRI contrast agent Mn2+. In vivo MRI studies revealed an obvious T1 contrast enhancement at the tumor site because of a combination of the EPR and active targeting effects. The PLTM-HMnO2 NPs led to effective inhibition of tumor growth, attributing to Fenton-like Mn2+ conversion of endogenous H2O2 in the tumor to highly toxic HO• and this anti-tumor efficacy was enhanced when combined with chemotherapy. These results indicate that the PLTM biomimetic HMnO2 nanoparticles are promising drug delivery systems for MRI-monitoring and enhanced targeted treatment of tumors.

AB - In this study, platelet membrane (PLTM) biomimetic hollow MnO2 nanoparticles were prepared and these were investigated for delivery of bufalin. Additionally, these nanoparticles, in response to the tumor microenvironment, showed rapid drug release and generated the hydroxyl radicals (HO•) by the Fenton reaction between Mn2+ and endogenous H2O2 for use in MRI-guided anti-tumor activity. Firstly, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were used to reduce KMnO4 to HMnO2 nanoparticles followed by acetone etching. After bufalin loading, these NPs were biomimetically cloaked with PLTM to form PLTM-HMnO2@Bu NPs. In vitro release profiles showed that the NPs responded to acid pH and glutathione (GSH) to induce decomposition of MnO2, resulting in rapid release of bufalin and yielding the MRI contrast agent Mn2+. In vivo MRI studies revealed an obvious T1 contrast enhancement at the tumor site because of a combination of the EPR and active targeting effects. The PLTM-HMnO2 NPs led to effective inhibition of tumor growth, attributing to Fenton-like Mn2+ conversion of endogenous H2O2 in the tumor to highly toxic HO• and this anti-tumor efficacy was enhanced when combined with chemotherapy. These results indicate that the PLTM biomimetic HMnO2 nanoparticles are promising drug delivery systems for MRI-monitoring and enhanced targeted treatment of tumors.

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