A mesoporous MnO2-based nanoplatform with near infrared light-controlled nitric oxide delivery and tumor microenvironment modulation for enhanced antitumor therapy

A hollow mesoporous manganese dioxide-based (H-MnO2) multifunctional nanoplatform, H-MnO2 @AFIPB@PDA@Ru-NO@FA (MAPRF NPs), was prepared for synergistic cancer treatment, in which a histone deacetylase inhibitor AFIPB was loaded in its hollow cavity and a ruthenium nitrosyl donor (Ru-NO) and a folic...

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Published inJournal of inorganic biochemistry Vol. 241; p. 112133
Main Authors Zhang, Hai-Lin, Wang, Yi, Tang, Qi, Ren, Bing, Yang, Shi-Ping, Liu, Jin-Gang
Format Journal Article
LanguageEnglish
Published Elsevier Inc 01.04.2023
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Abstract A hollow mesoporous manganese dioxide-based (H-MnO2) multifunctional nanoplatform, H-MnO2 @AFIPB@PDA@Ru-NO@FA (MAPRF NPs), was prepared for synergistic cancer treatment, in which a histone deacetylase inhibitor AFIPB was loaded in its hollow cavity and a ruthenium nitrosyl donor (Ru-NO) and a folic acid (FA) targeting group were covalently decorated on its covered polydopamine (PDA) layer. The MAPRF NPs showed tumor microenvironment (TME)-responsive properties of depletion of glutathione (GSH) to disrupt the antioxidant defense system and on-demand drug delivery. And the released Mn2+ further catalyzed the decomposition of endogenous H2O2 to produce highly toxic hydroxyl radicals (·OH) for enhanced chemodynamic therapy (CDT). Furthermore, upon 808 nm light irradiation MAPRF NPs exhibited controlled nitric oxide (NO) delivery and simultaneously produced significant photothermal effect. Consequently, MAPRF NPs showed high mortality toward cancer cells in the presence of 808 nm light irradiation. This work provides a paradigm of multimodal synergistic therapy that combines NO-based gas therapy with TME modulation for efficient antitumor therapy. A novel mesoporous MnO2-based multifunctional nanoplatform exhibited near-infrared light-controlled nitric oxide delivery, tumor microenvironment (TME)-responsive release of a histone deacetylase inhibitor and TME modulation for efficient multimodal synergistic antitumor therapy. [Display omitted] •A hollow mesoporous MnO2-based multifunctional NO-releasing nanoplatform was prepared.•Tumor microenvironment-responsive of GSH depletion and hydroxyl radical production.•Controlled NO delivery and photothermal effect was achieved upon 808 nm light irradiation.•It showed high mortality toward cancer cells under 808 nm light irradiation.•Synergistic multimodal therapies were attributed to the enhanced antitumor efficiency.
AbstractList A hollow mesoporous manganese dioxide-based (H-MnO2) multifunctional nanoplatform, H-MnO2 @AFIPB@PDA@Ru-NO@FA (MAPRF NPs), was prepared for synergistic cancer treatment, in which a histone deacetylase inhibitor AFIPB was loaded in its hollow cavity and a ruthenium nitrosyl donor (Ru-NO) and a folic acid (FA) targeting group were covalently decorated on its covered polydopamine (PDA) layer. The MAPRF NPs showed tumor microenvironment (TME)-responsive properties of depletion of glutathione (GSH) to disrupt the antioxidant defense system and on-demand drug delivery. And the released Mn2+ further catalyzed the decomposition of endogenous H2O2 to produce highly toxic hydroxyl radicals (·OH) for enhanced chemodynamic therapy (CDT). Furthermore, upon 808 nm light irradiation MAPRF NPs exhibited controlled nitric oxide (NO) delivery and simultaneously produced significant photothermal effect. Consequently, MAPRF NPs showed high mortality toward cancer cells in the presence of 808 nm light irradiation. This work provides a paradigm of multimodal synergistic therapy that combines NO-based gas therapy with TME modulation for efficient antitumor therapy. A novel mesoporous MnO2-based multifunctional nanoplatform exhibited near-infrared light-controlled nitric oxide delivery, tumor microenvironment (TME)-responsive release of a histone deacetylase inhibitor and TME modulation for efficient multimodal synergistic antitumor therapy. [Display omitted] •A hollow mesoporous MnO2-based multifunctional NO-releasing nanoplatform was prepared.•Tumor microenvironment-responsive of GSH depletion and hydroxyl radical production.•Controlled NO delivery and photothermal effect was achieved upon 808 nm light irradiation.•It showed high mortality toward cancer cells under 808 nm light irradiation.•Synergistic multimodal therapies were attributed to the enhanced antitumor efficiency.
ArticleNumber 112133
Author Wang, Yi
Ren, Bing
Liu, Jin-Gang
Zhang, Hai-Lin
Yang, Shi-Ping
Tang, Qi
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  givenname: Yi
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  givenname: Jin-Gang
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  fullname: Liu, Jin-Gang
  email: liujingang@ecust.edu.cn
  organization: Key Laboratory for Advanced Materials, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China
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Keywords NO
AFIPB
Tumor microenvironment modulation
EDC
MRI
MTT
PDA
Manganese dioxide
PTT
CDT
H-MnO2
RDPP
MB
FTIR
Ruthenium nitrosyl
NHS
OH
XPS
CLSM
GSH
Synergistic therapy
PBS
DTNB
Nitric oxide delivery
TME
BET
NPs
DCFH-DA
NIR
ROS
Fenton-like reaction
FA
TEM
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Snippet A hollow mesoporous manganese dioxide-based (H-MnO2) multifunctional nanoplatform, H-MnO2 @AFIPB@PDA@Ru-NO@FA (MAPRF NPs), was prepared for synergistic cancer...
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StartPage 112133
SubjectTerms Fenton-like reaction
Manganese dioxide
Nitric oxide delivery
Ruthenium nitrosyl
Synergistic therapy
Tumor microenvironment modulation
Title A mesoporous MnO2-based nanoplatform with near infrared light-controlled nitric oxide delivery and tumor microenvironment modulation for enhanced antitumor therapy
URI https://dx.doi.org/10.1016/j.jinorgbio.2023.112133
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