Proton nanomodulators for enhanced Mn 2+ -mediated chemodynamic therapy of tumors via HCO 3 - regulation.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, 2003-
    • Subject Terms:
      Tumor Microenvironment*/drug effects ; Bicarbonates*/chemistry ; Reactive Oxygen Species*/metabolism ; Manganese*/chemistry ; Manganese*/pharmacology; Animals ; Mice ; Humans ; Cell Line, Tumor ; Neoplasms/drug therapy ; Protons ; Mice, Inbred BALB C ; Ferric Compounds/chemistry ; Ferric Compounds/pharmacology ; Manganese Compounds/chemistry ; Manganese Compounds/pharmacology ; Nanoparticles/chemistry ; Glutathione/metabolism
    • Abstract:
      Background: Mn 2+ -mediated chemodynamic therapy (CDT) has been emerged as a promising cancer therapeutic modality that relies heavily on HCO 3 - level in the system. Although the physiological buffers (H 2 CO 3 /HCO 3 - ) provide certain amounts of HCO 3 - , the acidity of the tumor microenvironment (TME) would seriously affect the HCO 3 - ionic equilibrium (H 2 CO 3 ⇌ H + + HCO 3 - ). As a result, HCO 3 - level in the tumor region is actually insufficient to support effective Mn 2+ -mediated CDT.
      Results: In this study, a robust nanomodulator MnFe 2 O 4 @ZIF-8 (PrSMZ) with the capability of in situ self-regulation HCO 3 - is presented to enhance therapeutic efficacy of Mn 2+ -mediated CDT. Under an acidic tumor microenvironment, PrSMZ could act as a proton sponge to shift the HCO 3 - ionic equilibrium to the positive direction, significantly boosting the generation of the HCO 3 - . Most importantly, such HCO 3 - supply capacity of PrSMZ could be finely modulated by its ZIF-8 shell thickness, resulting in a 1000-fold increase in reactive oxygen species (ROS) generation. Enhanced ROS-dependent CDT efficacy is further amplified by a glutathione (GSH)-depletion ability and the photothermal effect inherited from the inner core MnFe 2 O 4 of PrSMZ to exert the remarkable antitumor effect on mouse models.
      Conclusions: This work addresses the challenge of insufficient HCO 3 - in the TME for Mn 2+ -mediated Fenton catalysts and could provide a promising strategy for designing high-performance Mn 2+ -mediated CDT agents to treat cancer effectively.
      (© 2024. The Author(s).)
    • References:
      Chem Rev. 2019 Apr 24;119(8):4881-4985. (PMID: 30973011)
      Adv Sci (Weinh). 2020 Sep 30;7(23):2000272. (PMID: 33304740)
      Nat Rev Cancer. 2017 Oct;17(10):577-593. (PMID: 28912578)
      J Am Chem Soc. 2023 Nov 8;145(44):24386-24400. (PMID: 37883689)
      ACS Nano. 2023 May 23;17(10):9529-9542. (PMID: 37154230)
      Angew Chem Int Ed Engl. 2004 Jan 16;43(4):483-5. (PMID: 14735541)
      Nano Lett. 2021 Jul 28;21(14):6042-6050. (PMID: 34254814)
      Small. 2022 Jun;18(25):e2200595. (PMID: 35599433)
      Nat Nanotechnol. 2019 Apr;14(4):379-387. (PMID: 30778211)
      J Am Chem Soc. 2024 Mar 6;146(9):6252-6265. (PMID: 38377559)
      Nano Lett. 2020 Sep 9;20(9):6780-6790. (PMID: 32809834)
      Org Lett. 2009 Feb 19;11(4):1019-22. (PMID: 19170624)
      Chem Soc Rev. 2017 Jun 21;46(12):3830-3852. (PMID: 28516983)
      J Am Chem Soc. 2020 Jan 29;142(4):1715-1720. (PMID: 31931564)
      Adv Sci (Weinh). 2020 Jun 14;7(17):2001060. (PMID: 32995124)
      Angew Chem Int Ed Engl. 2009;48(32):5875-9. (PMID: 19579243)
      Nat Commun. 2017 Aug 25;8(1):357. (PMID: 28842577)
      ACS Nano. 2019 Jan 22;13(1):187-202. (PMID: 30566836)
      Adv Mater. 2023 Jun;35(23):e2211205. (PMID: 36913539)
      Nat Chem. 2012 Feb 19;4(4):310-6. (PMID: 22437717)
      Mater Today Bio. 2024 May 20;26:101095. (PMID: 38840796)
      ACS Nano. 2009 Jun 23;3(6):1493-505. (PMID: 19449835)
      Nano Lett. 2021 Sep 22;21(18):7569-7578. (PMID: 34472343)
      Chem Soc Rev. 2022 Jul 18;51(14):6126-6176. (PMID: 35792076)
      Chem Sci. 2018 May 29;9(29):6210-6218. (PMID: 30090308)
      J Am Chem Soc. 2020 Sep 9;142(36):15320-15330. (PMID: 32820914)
      Small. 2011 Oct 4;7(19):2742-9. (PMID: 21861295)
      Adv Mater. 2021 Apr;33(17):e2100616. (PMID: 33760313)
      Angew Chem Int Ed Engl. 2017 Jun 6;56(24):6853-6858. (PMID: 28481003)
      Angew Chem Int Ed Engl. 2018 Apr 23;57(18):4902-4906. (PMID: 29488312)
    • Grant Information:
      23LLRH0070 Dual-chain Integration Special Program of Qin chuang yuan Construction; 2024JC-YBMS-181 Natural Science Basic Research Plan in Shaanxi Province of China; ZYTS24155 the Fundamental Research Funds for the Central Universities; 82272159, 91959124 and 32371433 National Natural Science Foundation of China; 82272159, 91959124 and 32371433 National Natural Science Foundation of China; 2023A1515030207 Guang Dong Basic and Applied Basic Research Foundation; 2022YFB3203800 the National Key Research and Development Program of China; 2022TD-52 Innovation Capability Support Program of Shaanxi; CBSKL2022ZDKF14 the Open Project Program of the State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers
    • Contributed Indexing:
      Keywords: Chemodynamic therapy; HCO3 −; Multi-level enhanced; Photothermal effect; Reactive oxygen species
    • Accession Number:
      0 (Bicarbonates)
      0 (Reactive Oxygen Species)
      42Z2K6ZL8P (Manganese)
      0 (Protons)
      0 (Ferric Compounds)
      0 (Manganese Compounds)
      0 (manganese ferrite)
      GAN16C9B8O (Glutathione)
    • Publication Date:
      Date Created: 20241102 Date Completed: 20241102 Latest Revision: 20241105
    • Publication Date:
      20241105
    • Accession Number:
      PMC11531122
    • Accession Number:
      10.1186/s12951-024-02843-4
    • Accession Number:
      39487480