Hydroxyl radical-involved cancer therapy via Fenton reactions

doi:10.1007/s11705-021-2077-3

Front. Chem. Sci. Eng.

2022, Vol. 16

Issue (3) : 345-363 https://doi.org/10.1007/s11705-021-2077-3

REVIEW ARTICLE

Hydroxyl radical-involved cancer therapy via Fenton reactions

Mengying Liu¹, Yun Xu², Yanjun Zhao¹, Zheng Wang¹(

), Dunyun Shi³(

)

¹. School of Pharmaceutical Science & Technology, Tianjin University, Tianjin 300072, China
². Central Lab, Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
³. Institute of Hematology, Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China

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Abstract

The tumor microenvironment features over-expressed hydrogen peroxide (H₂O₂). Thus, versatile therapeutic strategies based on H₂O₂ as a reaction substrate to generate hydroxyl radical (•OH) have been used as a prospective therapeutic method to boost anticancer efficiency. However, the limited Fenton catalysts and insufficient endogenous H₂O₂ content in tumor sites greatly hinder •OH production, failing to achieve the desired therapeutic effect. Therefore, supplying Fenton catalysts and elevating H₂O₂ levels into cancer cells are effective strategies to improve •OH generation. These therapeutic strategies are systematically discussed in this review. Furthermore, the challenges and future developments of hydroxyl radical-involved cancer therapy are discussed to improve therapeutic efficacy.

Keywords hydroxyl radical Fenton catalyst hydrogen peroxide cancer therapy

Corresponding Author(s): Zheng Wang,Dunyun Shi

Online First Date: 09 September 2021 Issue Date: 24 February 2022

Cite this article:

Mengying Liu,Yun Xu,Yanjun Zhao, et al. Hydroxyl radical-involved cancer therapy via Fenton reactions[J]. Front. Chem. Sci. Eng., 2022, 16(3): 345-363.

URL:

https://academic.hep.com.cn/fcse/EN/10.1007/s11705-021-2077-3
https://academic.hep.com.cn/fcse/EN/Y2022/V16/I3/345

Fig.1 Schematic illustration of •OH-mediated cancer therapy.

Material	Functional mechanism	Cell	Ref.
IONPs	Fe²⁺-mediated •OH generation	HT1080	[34]
JFSNs-GOx	GOx-catalyzed H₂O₂ generation; Fe²⁺-mediated •OH generation	4T1	[35]
CPT@MOF(Fe)-GOx	GOx-catalyzed H₂O₂ generation; Fe²⁺-mediated •OH generation; CPT-mediated chemotherapy	HeLa	[36]
rFeO_x-HMSN	Fe²⁺-mediated •OH generation	4T1	[37]
LET-6	Fe²⁺-mediated •OH generation; tPy-Cy-Fe-mediated photothermal therapy	U87MG	[38]
Fe₅C₂@Fe₃O₄ NPs	Fe²⁺-mediated •OH generation	4T1	[39]
FDMSNs@GOx@HA	GOx-catalyzed H₂O₂ generation; Fe²⁺-mediated •OH generation	L-02; HeLa	[40]
Fe-CO@Mito-PNBE	CO-mediated gas therapy; Fe²⁺-mediated •OH generation	4T1; HeLa	[41]
CuS-Fe@polymer	Fe²⁺-mediated •OH generation; CuS-mediated photothermal therapy	HeLa; NIH3T3	[42]
Co-Fc@GOx	GOx-catalyzed H₂O₂ generation; Fe²⁺-mediated •OH generation	HUVEC; 4T1	[43]
Zr-Fc MOF	Zr-Fc MOF-mediated photothermal therapy; Fe²⁺-mediated •OH generation	7702; 4T1; Huh7	[44]
CFNCs	Fe²⁺-mediated •OH generation; PTX-mediated chemotherapy	HCT-15; NIH3T3	[45]
GOx&Pt@FcNV	GOx-catalyzed H₂O₂ generation; Fe²⁺-mediated •OH generation; Pt-mediated chemotherapy	A549; MCF7	[46]
GOx@ZIF@MPN	GOx-catalyzed H₂O₂ generation; Fe²⁺-mediated •OH generation	4T1	[47]
BSO/GA-Fe(II)@liposome	BSO-mediated GSH synthesis inhibition; Fe²⁺-mediated •OH generation	4T1	[48]
SRF@Fe^IIITA	SRF-mediated GSH synthesis inhibition; Fe²⁺-mediated •OH generation	4T1; CT26; HepG2; 3T3; COS7; NCTC 1469	[49]
Fe³⁺-DOX@EGCG-PEG NPs	DOX-mediated chemotherapy; Fe²⁺-mediated •OH generation	U87MG; 293T	[50]
DOX/Fe³⁺/EGCG NPs	DOX-mediated chemotherapy; Fe²⁺-mediated •OH generation	LL2; A549	[51]
MnS@BSA	H₂S-mediated gas therapy; Mn²⁺-mediated •OH generation	4T1	[52]
GOx-MnCaP-DOX	GOx-catalyzed H₂O₂ generation; Mn²⁺-mediated •OH generation; DOX-mediated chemotherapy	4T1	[53]
GNR@SiO₂@MnO₂	Mn²⁺-mediated •OH generation; GSM-mediated photothermal therapy	U87MG	[54]
BMC-DOX	Mn²⁺-mediated •OH generation; DOX-mediated chemotherapy	4T1; U87MG	[55]
GMCD	GOx-catalyzed H₂O₂ generation; Mn²⁺-mediated •OH generation; CAT-mediated O₂ generation; DVDMS-mediated ¹O₂ generation	4T1	[56]
MS@MnO₂?NPs	MnO₂-mediated GSH depletion; Mn²⁺-mediated •OH generation	U87MG	[57]
PCN-224(Cu)-GOD@MnO₂	MnO₂-mediated O₂ supply; GOD-mediated H₂O₂ generation; Cu⁺-mediated •OH generation	L929; HeLa	[58]
Cu_2–_xS-PEG NDs	Cu_2–_xS-mediated photothermal therapy; Cu⁺-mediated •OH generation	4T1	[59]
PEG-Cu₂Se HNCs	Cu₂Se-mediated photothermal therapy; Cu⁺-mediated •OH generation	HUVECs; 4T1	[60]
PGC-DOX	GOx-catalyzed H₂O₂ generation; Cu²⁺-mediated GSH depletion; Cu⁺-mediated •OH generation; DOX-mediated chemotherapy	4T1	[61]
SC@G NSs	GOx-catalyzed H₂O₂ generation; Sr⁺/Cu⁺-mediated •OH generation; SC NSs-mediated photothermal therapy	4T1; 293T	[62]
Cu-Cys NPs	Cu²⁺-mediated GSH depletion; Cu⁺-mediated •OH generation	HeLa; MCF-7; PC-3; hADSCs; hbMSCs; HK-2	[63]
GOD-Fe₃O₄@DMSNs	GOD-catalyzed H₂O₂ generation; Fe²⁺-mediated •OH generation	4T1; U87	[64]
MNS-GOx	GOx-catalyzed H₂O₂ generation; Mn²⁺-mediated •OH generation	A375	[65]
Fe₅C₂-GOD@MnO₂	MnO₂-mediated O₂ supply; GOD-mediated H₂O₂ generation; Fe²⁺-mediated •OH generation	HeLa	[66]
PEG-Au/FeMOF@CPT NPs	Au-catalyzed H₂O₂ generation; Fe²⁺-mediated •OH generation; CPT-mediated chemotherapy	HepG2	[67]
DMSN-Au-Fe₃O₄-PEG?NPs	Au-catalyzed H₂O₂ generation; Fe²⁺-mediated •OH generation	4T1	[68]
Fe₃O₄@PEI-Pt(IV)-PEG	SOD-catalyzed H₂O₂ generation; Fe²⁺-mediated •OH generation; Pt-mediated chemotherapy	A2780; ACP	[69]
PZIF67-AT	As nanozyme, ZIF-67-mediated H₂O₂ generation, •OH generation, and GSH depletion; 3-AT-mediated H₂O₂ elimination inhibition	A549; HeLa; 4T1	[70]
PA/Fc-Micelles	Asc-mediated H₂O₂ generation; Fe²⁺-mediated •OH generation	4T1; MCF-7	[71]
CaP-Fe/RSL3+ Asc	Asc-mediated H₂O₂ generation; Fe²⁺-mediated •OH generation; RSL3-mediated GPX4 inhibition	4T1	[72]
CaO₂-Fe₃O₄@HA NPs	CaO₂-mediated H₂O₂ generation; Fe²⁺-mediated •OH generation	4T1; NIH/3T3; LO2; MCF-7	[73]
Nb₂C-IO-CaO₂-PVP	CaO₂-mediated H₂O₂ generation; Fe²⁺-mediated •OH generation	4T1	[74]
CP nanodots	CP nanodots -mediated H₂O₂ generation and •OH generation	U87MG	[75]
Fe-GA/CaO₂@PCM	PCMs-mediated photothermal-responsive gatekeeper; CaO₂-mediated H₂O₂ generation; Fe²⁺-mediated •OH generation	HeLa	[76]
HA-CD/Fc-CA NPs	CA-mediated H₂O₂ generation; Fe²⁺-mediated •OH generation	MCF-7; 4T1; NIH/3T3	[77]
PolyCAFe	CA-mediated H₂O₂ generation; Fe²⁺-mediated •OH generation	SW620; DU145; HEK293; NIH3T3	[78]
LaCIONPs	La-mediated H₂O₂ generation; Fe²⁺-mediated •OH generation; CPT-mediated chemotherapy	A549	[79]
PtkDOX-NMs	La-mediated H₂O₂ generation; Fe²⁺-mediated •OH generation; DOX-mediated chemotherapy	A549	[80]
Fe₃O₄-HSA@Lapa	La-mediated H₂O₂ generation; Fe²⁺-mediated •OH generation	A549	[81]
Fe@Fe₃O₄@Cu_2–_xS@La-PEG	La-mediated H₂O₂ generation; Fe@Fe₃O₄@Cu_2–_xS-PEG-mediated •OH generation	4T1; HUVE	[82]

Tab.1 The supply of Fenton catalysts and elevation of H₂O₂ level for enhanced •OH generation ^a)

Fig.2 Three typical metal-based catalysts for the Fenton reaction.

Fig.8 Schematic illustration of various strategies to boost H₂O₂ generation.

Fig.12 Schematic representation of (a) the synthesis of PZIF67-AT NPs and (b) PZIF67-AT NPs-mediated intensive •OH production. Reprinted with permission from ref. [70]. Copyright 2020, American Chemical Society.

Fig.15 Schematic diagram of the PolyCAFe-triggered cancer apoptosis via boosting H₂O₂ generation and •OH generation. Reprinted with permission from ref. [78]. Copyright 2016, American Chemical Society.

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