Malignant tumors pose a serious threat to human health. They are characterized by high incidence and indistinct early symptoms. Advances in medical technology have revealed the limitations of conventional therapies. Consequently, precision, minimally invasive, and integrated diagnosis and treatment have become key objectives in modern oncology. Nanomedicine shows considerable potential for precision therapy. However, novel nanocarriers that combine high efficiency, precise targeting, controllable drug release, and excellent biocompatibility are still urgently needed. Hollow manganese dioxide is a promising inorganic nanomaterial. It exhibits high drug loading capacity, responsiveness to the tumor microenvironment, and favorable biocompatibility. These properties make it an excellent drug carrier for cancer therapy. Synthetic methods for constructing MnO2-based multifunctional nanoplatforms continue to advance. This review highlights promising applications of hollow MnO2 in drug delivery, bioimaging, and biosensing. Finally, we summarize the associated challenges and future prospects in anticancer applications, aiming to provide meaningful guidance for further research.p
SiegelRLMillerKDWagleNS, et al.Cancer statistics, 2023. CA Cancer J Clin2023; 73(1): 17–48.
2.
WaksAGWinerEP. Breast cancer treatment: a review. JAMA2019; 321(3): 288–300.
3.
KaurRBhardwajAGuptaS. Cancer treatment therapies: traditional to modern approaches to combat cancers. Mol Biol Rep2023; 50(11): 9663–9676.
4.
AbreuDBCernadasJR. Management of adverse reactions induced by chemotherapy drugs. Curr Opin Allergy Clin Immunol2022; 22(4): 221–225.
5.
GowdVAhmadATariqueM, et al.Advancement of cancer immunotherapy using nanoparticles-based nanomedicine. Semin Cancer Biol2022; 86: 624–644.
6.
XiangJZhaoRWangB, et al.Advanced nano-carriers for anti-tumor drug loading. Front Oncol2021; 11: 758143.
7.
KongXXieXWuJ, et al.Combating cancer immunotherapy resistance: a nano‐medicine perspective. Cancer Commun2025; 45(7): 813–840.
8.
AnwarMGumaahNFRagabAH, et al.Enhancing the photocatalytic and biological potential of MnO nanoparticles through strontium doping. J Mol Struct2025; 1343: 142872.
GaoRXiaDZhangX, et al.Synergistic enhancement of therapeutic efficacy in acute myocardial infarction via nanoflower-like Mn3O4 nanozymes in coordination with adipose-derived stem cell transplantation. Int J Nanomed2025; 20: 2073–2086.
11.
SaidMIAbdel-aalFAMRagehAH. Novel sponge-like Mn5O8 nanoparticles deposited on graphite electrode for electrochemical study of hepatitis C antiviral drug, elbasvir. Microchem J2020; 157: 105056.
12.
XiaHYLiBYZhaoY, et al.Nanoarchitectured manganese dioxide (MnO2)-based assemblies for biomedicine. Coord Chem Rev2022; 464: 214540.
13.
ChengMYuYHuangW, et al.Monodisperse hollow MnO2 with biodegradability for efficient targeted drug delivery. ACS Biomater Sci Eng2020; 6(9): 4985–4992.
14.
WangZWuCLiuJ, et al.Aptamer-mediated hollow MnO2 for targeting the delivery of sorafenib. Drug Deliv2023; 30(1): 28–39.
15.
YuYFWuECLinSQ, et al.Reexamining the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin. Acta Pharmacol Sin2024; 45(3): 646–659.
16.
ShettimaAKZahoorAShergujriDA, et al.Liposome as drug delivey systems. Int J Pharmaceut Res Anal2025; 10(4): 1069–1082.
17.
Sonam DongsarTTsering DongsarTMoluguluN, et al.Targeted therapy of breast tumor by PLGA-based nanostructures: the versatile function in doxorubicin delivery. Environ Res2023; 233: 116455.
18.
ChoiYYoonHYKimJ, et al.Doxorubicin-loaded PLGA nanoparticles for cancer therapy: molecular weight effect of PLGA in doxorubicin release for controlling immunogenic cell death. Pharmaceutics2020; 12(12): 1165.
19.
QamarMAbbasGAfzaalM, et al.Gold nanorods for doxorubicin delivery: numerical analysis of electric field enhancement, optical properties and drug loading/releasing efficiency. Materials2022; 15(5): 1764.
20.
ExnerKSIvanovaA. A doxorubicin–peptide–gold nanoparticle conjugate as a functionalized drug delivery system: exploring the limits. Phys Chem Chem Phys2022; 24(24): 14985–14992.
21.
MosseriASanchez-UrielLGarcia-PeiroJI, et al.A review of silica-based nanoplatforms for anticancer cargo delivery. Int J Mol Sci2025; 26(12): 5850.
22.
SunHDongSKongL, et al.Cationic anticancer peptide L-K6-modified and doxorubicin-loaded mesoporous silica nanoparticles reverse multidrug resistance of breast cancer. Arab J Chem2024; 17(5): 105735.
23.
SarkarPMannaABeraS, et al.Chitosan nanocarriers: a promising approach for glioblastoma therapy. Carbohydr Polym2025; 365: 123823.
24.
HuangSJWangTHChouYH, et al.Hybrid PEGylated chitosan/PLGA nanoparticles designed as pH-responsive vehicles to promote intracellular drug delivery and cancer chemotherapy. Int J Biol Macromol2022; 210: 565–578.
25.
AkhtarHAmaraUMahmoodK, et al.Drug carrier wonders: synthetic strategies of zeolitic imidazolates frameworks (ZIFs) and their applications in drug delivery and anti-cancer activity. Adv Colloid Interface Sci2024; 329: 103184.
26.
LeBQGDoanTLH. Trend in biodegradable porous nanomaterials for anticancer drug delivery. WIREs Nanomedicine and Nanobiotechnology2023; 15(4): e1874.
27.
XuXDuanJLiuY, et al.Multi-stimuli responsive hollow MnO2-based drug delivery system for magnetic resonance imaging and combined chemo-chemodynamic cancer therapy. Acta Biomater2021; 126: 445–462.
28.
KunduMButtiRPandaVK, et al.Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer. Mol Cancer2024; 23(1): 92.
29.
QuaziMZParkJParkN. Phototherapy: a conventional approach to overcome the barriers in oncology therapeutics. Technol Cancer Res Treat2023; 22: 15330338231170939.
30.
MengXSunZChuH, et al.Self-assembled nanoplatforms for chemodynamic therapy. Chem Eng J2024; 479: 147702.
31.
ZareAShamshiripourPLotfiS, et al.Clinical theranostics applications of photo-acoustic imaging as a future prospect for cancer. J Contr Release2022; 351: 805–833.
32.
YuanSZhouJWangJ, et al.Advances of photothermal agents with fluorescence imaging/enhancement ability in the field of photothermal therapy and diagnosis. Mol Pharm2024; 21(2): 467–480.
33.
LiangYZhangMZhangY, et al.Ultrasound sonosensitizers for tumor sonodynamic therapy and imaging: a new direction with clinical translation. Molecules2023; 28(18): 6484.
34.
HenoumontCDevreuxMLaurentS. Mn-based MRI contrast agents: an overview. Molecules2023; 28(21): 7275.
35.
RuanJQianH. Recent development on controlled synthesis of Mn-based nanostructures for bioimaging and cancer therapy. Adv Therapeut2021; 4(5): 2100018.
36.
NguyenNTHTranGTNguyenNTT, et al.A critical review on the biosynthesis, properties, applications and future outlook of green MnO2 nanoparticles. Environ Res2023; 231: 116262.
37.
BurtonAJThomsonARDawsonWM, et al.Installing hydrolytic activity into a completely de novo protein framework. Nat Chem2016; 8(9): 837–844.
38.
ChenGYanSOuyangC, et al.A new hydrogel to promote healing of bacteria infected wounds: enzyme-like catalytic activity based on MnO2 nanocrytal. Chem Eng J2023; 470: 143986.
39.
HuangPTangQLiM, et al.Manganese-derived biomaterials for tumor diagnosis and therapy. J Nanobiotechnol2024; 22(1): 335.
40.
GreeneAHashemiJKangY. Development of MnO2 hollow nanoparticles for potential drug delivery applications. Nanotechnology2020; 32(2): 025713.
41.
ZhaoDWeiYXiongJ, et al.Response and regulation of the microenvironment based on hollow structured drug delivery systems. Adv Funct Mater2023; 33(31): 2300681.
42.
WangCZhangS. Advantages of nanomedicine in cancer therapy: a review. ACS Appl Nano Mater2023; 6(24): 22594–22610.
43.
ZhangLZhaiBZWuYJ, et al.Recent progress in the development of nanomaterials targeting multiple cancer metabolic pathways: a review of mechanistic approaches for cancer treatment. Drug Deliv2023; 30(1): 1–18.
44.
GaoWBighamAGhomiM, et al.Micelle-engineered nanoplatforms for precision oncology. Chem Eng J2024; 495: 153438.
45.
ZhengYOzYGuY, et al.Rational design of polymeric micelles for targeted therapeutic delivery. Nano Today2024; 55: 102147.
46.
Truong HoangQNguyen CaoTGKangSJ, et al.Exosome membrane-sheathed and multi-stimuli-responsive MnO2 nanoparticles with self-oxygenation and energy depletion abilities potentiate the sonodynamic therapy of hypoxic tumors. Chem Eng J2023; 472: 144871.
47.
AndersonNMSimonMC. The tumor microenvironment. Curr Biol2020; 30(16): R921–R925.
48.
SongKJiangCHuangS, et al.Exogenous/endogenous stimuli-responsive nanocatalysts trigger in situ chemical reactions for tumor catalytic therapy: an up-to-date mini-review. Mater Chem Front2025; 9(2): 189–203.
49.
LiJGongCChenX, et al.Biomimetic liposomal nanozymes improve breast cancer chemotherapy with enhanced penetration and alleviated hypoxia. J Nanobiotechnol2023; 21(1): 123.
XiaoYYuD. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther2021; 221: 107753.
52.
YuanPDengFLiuY, et al.Mitochondria targeted O2 economizer to alleviate tumor hypoxia for enhanced photodynamic therapy. Adv Healthcare Mater2021; 10(12): 2100198.
53.
NajafiAKeykhaeeMKhorramdelazadH, et al.Catalase application in cancer therapy: simultaneous focusing on hypoxia attenuation and macrophage reprogramming. Biomed Pharmacother2022; 153: 113483.
54.
ChenXZhangXWuY, et al.Tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy. Mater Today2022; 61: 78–90.
GalassoMGambinoSRomanelliMG, et al.Browsing the oldest antioxidant enzyme: catalase and its multiple regulation in cancer. Free Radic Biol Med2021; 172: 264–272.
57.
JoSMWurmFRLandfesterK. Oncolytic nanoreactors producing hydrogen peroxide for oxidative cancer therapy. Nano Lett2019; 20(1): 526–533.
58.
ZhangYZhangJJiaQ, et al.Innovative strategies of hydrogen peroxide-involving tumor therapeutics. Mater Chem Front2021; 5(12): 4474–4501.
59.
ChenBCaiLFanR, et al.Multifunctional Ce6-loaded MnO2 as an oxygen-elevated nanoplatform for synergistic photodynamic/photothermal therapy. Mater Des2023; 227: 111702.
60.
WangZLiuJZhouZ, et al.Cell membrane-coated hollow manganese dioxide drug delivery nanosystem for targeted liver cancer diagnosis and treatment. ACS Appl Nano Mater2023; 7(16): 18262–18272.
61.
LiuJZhuHLinL, et al.Redox imbalance triggered intratumoral cascade reaction for tumor “turn on” imaging and synergistic therapy. Small2023; 19(16): 2206272.
62.
PiFDengXXueQ, et al.Alleviating the hypoxic tumor microenvironment with MnO2-coated CeO2 nanoplatform for magnetic resonance imaging guided radiotherapy. J Nanobiotechnol2023; 21(1): 90.
63.
HanJMaHAiS, et al.Mn-ZIF nanozymes kill tumors by generating hydroxyl radical as well as reversing the tumor microenvironment. Front Pharmacol2024; 15(000): 1441818.
64.
LiaoSWuGXieZ, et al.pH regulators and their inhibitors in tumor microenvironment. Eur J Med Chem2024; 267: 116170.
65.
ZhangWWangYGuM, et al.Manganese nanosheets loaded with selenium and gemcitabine activate the tumor microenvironment to enhance anti-tumor immunity. J Colloid Interface Sci2025; 682: 556–567.
66.
LvHZhenCLiuJ, et al.Unraveling the potential role of glutathione in multiple forms of cell death in cancer therapy. Oxid Med Cell Longev2019; 2019(1): 3150145.
67.
MartinsACOliveira-PaulaGHTinkovAA, et al.Role of manganese in brain health and disease: focus on oxidative stress. Free Radic Biol Med2025; 232: 306–318.
68.
ZunCSJessieJ. Superparamagnetic iron oxide tracer on breast MRI. Journal of Breast Imaging2024; 6(1): 106–108.
69.
ChenYQiYWangK. Neoadjuvant chemotherapy for breast cancer: an evaluation of its efficacy and research progress. Front Oncol2023; 13: 1169010.
70.
FreitasVLiXAmitaiY, et al.Contralateral breast screening with preoperative MRI: long-term outcomes for newly diagnosed breast cancer. Radiology2022; 304(2): 297–307.
71.
XiaoZChanLZhangD, et al.Precise delivery of a multifunctional nanosystem for MRI-guided cancer therapy and monitoring of tumor response by functional diffusion-weighted MRI. J Mater Chem B2019; 7(18): 2926–2937.
72.
ZhengRGuoJCaiX, et al.Manganese complexes and manganese-based metal-organic frameworks as contrast agents in MRI and chemotherapeutics agents: applications and prospects. Colloids Surf B Biointerfaces2022; 213: 112432.
73.
GongYHuXChenM, et al.Recent progress of iron-based nanomaterials in gene delivery and tumor gene therapy. J Nanobiotechnol2024; 22(1): 309.
74.
LiuJGuoCLiC, et al.Redox/pH-responsive hollow manganese dioxide nanoparticles for thyroid cancer treatment. Front Chem2023; 11: 1249472.
75.
BritoBRuggieroMRPriceTW, et al.Redox double-switch cancer theranostics through Pt(IV) functionalised manganese dioxide nanostructures. Nanoscale2023; 15(25): 10763–10775.
76.
FarooqASabahSDhouS, et al.Exogenous contrast agents in photoacoustic imaging: an in vivo review for tumor imaging. Nanomaterials2022; 12(3): 393.
77.
FarajollahiABaharvandM. Advancements in photoacoustic imaging for cancer diagnosis and treatment. Int J Pharm2024; 665: 124736.
78.
HesterSCKuriakoseMNguyenCD, et al.Role of ultrasound and photoacoustic imaging in photodynamic therapy for cancer. Photochem Photobiol2020; 96(2): 260–279.
79.
LiLLiSFanZ, et al.Current strategies of photoacoustic imaging assisted cancer theragnostics toward clinical studies. ACS Photonics2022; 9(8): 2555–2578.
80.
KnoxHJChanJ. Acoustogenic probes: a new frontier in photoacoustic imaging. Acc Chem Res2018; 51(11): 2897–2905.
81.
PengJDongMRanB, et al.“One-for-all”-type, biodegradable prussian blue/manganese dioxide hybrid nanocrystal for trimodal imaging-guided photothermal therapy and oxygen regulation of breast cancer. ACS Appl Mater Interfaces2017; 9(16): 13875–13886.
82.
YuwenLXiaoHLuP, et al.Amylase degradation enhanced NIR photothermal therapy and fluorescence imaging of bacterial biofilm infections. Biomater Sci2023; 11(2): 630–640.
83.
WooYChaurasiyaSO’LearyM, et al.Fluorescent imaging for cancer therapy and cancer gene therapy. Mol Ther Oncolytics2021; 23: 231–238.
84.
YeungTM. Fluorescence imaging in colorectal surgery. Surg Endosc2021; 35(9): 4956–4963.
85.
JiYJonesCBaekY, et al.Near-infrared fluorescence imaging in immunotherapy. Adv Drug Deliv Rev2020; 167: 121–134.
86.
WangSRenWXHouJT, et al.Fluorescence imaging of pathophysiological microenvironments. Chem Soc Rev2021; 50(16): 8887–8902.
87.
DuanQJZhaoZYZhangYJ, et al.Activatable fluorescent probes for real-time imaging-guided tumor therapy. Adv Drug Deliv Rev2023; 196: 114793.
88.
LiuJZhangMWuY. In situ synthesis of fluorescent polydopamine on biogenic MnO2 nanoparticles as stimuli responsive multifunctional theranostics. Biomater Sci2021; 9(17): 5897–5906.
89.
SunDSunXZhangX, et al.Emerging chemodynamic nanotherapeutics for cancer treatment. Adv Healthcare Mater2024; 13(22): 2400809.
90.
ManivasaganPJoeAHanHW, et al.Recent advances in multifunctional nanomaterials for photothermal-enhanced Fenton-based chemodynamic tumor therapy. Mater Today Bio2022; 13: 100197.
91.
LiuPPengYDingJ, et al.Fenton metal nanomedicines for imaging-guided combinatorial chemodynamic therapy against cancer. Asian J Pharm Sci2022; 17(2): 177–192.
92.
WangZLiZShiY, et al.Mesoporous polydopamine delivery system for intelligent drug release and photothermal-enhanced chemodynamic therapy using MnO2 as gatekeeper. Regen Biomater2023; 10: rbad087.
93.
ZhangLYangZHeW, et al.One-pot synthesis of a self-reinforcing cascade bioreactor for combined photodynamic/chemodynamic/starvation therapy. J Colloid Interface Sci2021; 599: 543–555.
94.
ZhangHLWangYTangQ, et al.A mesoporous MnO2-based nanoplatform with near infrared light-controlled nitric oxide delivery and tumor microenvironment modulation for enhanced antitumor therapy. J Inorg Biochem2023; 241: 112133.
95.
ChengSShiYSuC, et al.MnO2 nanosheet-mediated generalist probe: cancer-targeted dual-microRNAs detection and enhanced CDT/PDT synergistic therapy. Biosens Bioelectron2022; 214: 114550.
96.
XuYTanWChenM, et al.MnO2 coated multi-layer nanoplatform for enhanced sonodynamic therapy and MR imaging of breast cancer. Front Bioeng Biotechnol2022; 10: 955127.
97.
NingYZhangZYasenA, et al.Hyaluronic acid-modified hollow MnO2-Loaded IR780 smart Theranostic platform for dual imaging guided sonodynamic therapy. Colloids Surf A Physicochem Eng Asp2025; 727: 138224.
98.
ShiYShiYWangZ, et al.Glucose-responsive mesoporous prussian blue nanoprobes coated with ultrasmall gold and manganese dioxide for magnetic resonance imaging and enhanced antitumor therapy. Chem Eng J2023; 453: 139885.
99.
FuLZhangWZhouX, et al.Tumor cell membrane-camouflaged responsive nanoparticles enable MRI-guided immuno-chemodynamic therapy of orthotopic osteosarcoma. Bioact Mater2022; 17: 221–233.
100.
DuBBaiYJiaoQ, et al.Simultaneous innate immunity activation and immunosuppression improvement by biodegradable nanoplatform for boosting antitumor chemo-immunotherapy. Chem Eng J2022; 441: 136093.
101.
DuSChenCQuS, et al.DNAzyme‐assisted nano‐herb delivery system for multiple tumor immune activation. Small2022; 18(45): 2203942.
102.
LiXLuoSChenY, et al.Facile one-pot synthesis of meteor hammer-like Au-MnOx nanozymes with spiky surface for NIR-II light-enhanced bacterial elimination. Chem Mater2022; 34(22): 9876–9891.
103.
LiXPanYZhouJ, et al.Hyaluronic acid-modified manganese dioxide-enveloped hollow copper sulfide nanoparticles as a multifunctional system for the co-delivery of chemotherapeutic drugs and photosensitizers for efficient synergistic antitumor treatments. J Colloid Interface Sci2022; 605: 296–310.
104.
WuMChenTWangL, et al.The strategy of precise targeting and in situ oxygenating for enhanced triple-negative breast cancer chemophototherapy. Nanoscale2022; 14(23): 8349–8361.
105.
DaiYLiXXueY, et al.Self-delivery of metal-coordinated NIR-II nanoadjuvants for multimodal imaging-guided photothermal-chemodynamic amplified immunotherapy. Acta Biomater2023; 166: 496–511.
106.
YuSChenZZengX, et al.Advances in nanomedicine for cancer starvation therapy. Theranostics2019; 9(26): 8026–8047.
107.
LiZLiXAiS, et al.Glucose metabolism intervention-facilitated nanomedicine therapy. Int J Nanomed2022; 17: 2707–2731.
108.
BianWWangYPanZ, et al.Review of functionalized nanomaterials for photothermal therapy of cancers. ACS Appl Nano Mater2021; 4(11): 11353–11385.
109.
HuZZhouXZhangW, et al.Photothermal amplified multizyme activity for synergistic photothermal-catalytic tumor therapy. J Colloid Interface Sci2025; 679: 375–383.
110.
NaikGARRGuptaADattaD, et al.Synergistic combinational photothermal therapy-based approaches for cancer treatment. FlatChem2025; 50: 100834.
111.
JiangJHuJLiM, et al.NIR-II fluorescent thermophoretic nanomotors for superficial tumor photothermal therapy. Adv Mater2025; 37(10): e2417440.
112.
ShiMLiuXPanW, et al.Anti-inflammatory strategies for photothermal therapy of cancer. J Mater Chem B2023; 11(28): 6478–6490.
113.
ChenYZhouFWangC, et al.Nanostructures as photothermal agents in tumor treatment. Molecules2022; 28(1): 277.
YunWSParkJHLimDK, et al.How did conventional nanoparticle-mediated photothermal therapy become “hot” in combination with cancer immunotherapy?Cancers2022; 14(8): 2044.
116.
CorreiaJHRodriguesJAPimentaS, et al.Photodynamic therapy review: principles, photosensitizers, applications, and future directions. Pharmaceutics2021; 13(9): 1332.
117.
ChongLMTngDJHTanLLY, et al.Recent advances in radiation therapy and photodynamic therapy. Appl Phys Rev2021; 8(4): 041322.
118.
LiuXPanXWangC, et al.Modulation of reactive oxygen species to enhance sonodynamic therapy. Particuology2023; 75: 199–216.
119.
GongZDaiZ. Design and challenges of sonodynamic therapy system for cancer theranostics: from equipment to sensitizers. Adv Sci2021; 8(10): 2002178.
120.
ZhaoPDengYXiangG, et al.Nanoparticle-assisted sonosensitizers and their biomedical applications. Int J Nanomed2021; 16: 4615–4630.
121.
MaXChenBWuH, et al.A tumour microenvironment-mediated Bi2-xMnxO3 hollow nanospheres via glutathione depletion for photothermal enhanced chemodynamic collaborative therapy. J Mater Chem B2022; 10(18): 3452–3461.
122.
CaoCWangXYangN, et al.Recent advances of cancer chemodynamic therapy based on Fenton/fenton-like chemistry. Chem Sci2022; 13(4): 863–889.
123.
JanaDZhaoY. Strategies for enhancing cancer chemodynamic therapy performance. Explorations2022; 2(2): 20210238.
124.
MaripuriSJohansenKL. Risk of gadolinium-based contrast agents in chronic kidney disease—Is zero good enough?JAMA Intern Med2020; 180(2): 230–232.
125.
RibasAWolchokJD. Cancer immunotherapy using checkpoint blockade. Science2018; 359(6382): 1350–1355.
126.
JenkinsSWesolowskiRGatti-MaysME. Improving breast cancer responses to immunotherapy-a search for the achilles heel of the tumor microenvironment. Curr Oncol Rep2021; 23(5): 55.
127.
MantoothSMAbdouYSaez-IbañezAR, et al.Intratumoral delivery of immunotherapy to treat breast cancer: current development in clinical and preclinical studies. Front Immunol2024; 15: 1385484.
128.
OzpiskinOMZhangLLiJJ. Immune targets in the tumor microenvironment treated by radiotherapy. Theranostics2019; 9(5): 1215–1231.
129.
GarrisCSLukeJJ. Dendritic cells, the T-cell-inflamed tumor microenvironment, and immunotherapy treatment response. Clin Cancer Res2020; 26(15): 3901–3907.
130.
YeFDewanjeeSLiY, et al.Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer. Mol Cancer2023; 22(1): 105.
131.
HenzeATMazzoneM. The impact of hypoxia on tumor-associated macrophages. J Clin Investig2016; 126(10): 3672–3679.
132.
MikhailASMorhardRMauda-HavakukM, et al.Hydrogel drug delivery systems for minimally invasive local immunotherapy of cancer. Adv Drug Deliv Rev2023; 202: 115083.
133.
WangJJiangWFangM, et al.Monocarboxylate transporter blockage-enabled lactate redistribution reshapes immunosuppressive tumor microenvironment and enhances chemodynamic immunotherapy. Chem Eng J2023; 477: 147163.
134.
ZhaoZDongSLiuY, et al.Tumor microenvironment-activable manganese-boosted catalytic immunotherapy combined with PD-1 checkpoint blockade. ACS Nano2022; 16(12): 20400–20418.
135.
ZhangTHuCZhangW, et al.Advances of MnO2 nanomaterials as novel agonists for the development of cGAS-STING-mediated therapeutics. Front Immunol2023; 14: 1156239.
136.
ZhangMZouYZhouX, et al.Inhibitory targeting cGAS-STING-TBK1 axis: emerging strategies for autoimmune diseases therapy. Front Immunol2022; 13: 954129.
ChangCCDinhTKLeeYA, et al.Nanoparticle delivery of MnO2 and antiangiogenic therapy to overcome hypoxia-driven tumor escape and suppress hepatocellular carcinoma. ACS Appl Mater Interfaces2020; 12(40): 44407–44419.
139.
DengCChenDYangL, et al.The role of cGAS-STING pathway ubiquitination in innate immunity and multiple diseases. Front Immunol2025; 16: 1522200.
140.
FengDKangXWangH, et al.Photochemical bomb: precision nuclear targeting to activate cGAS-STING pathway for enhanced bladder cancer immunotherapy. Biomaterials2025; 318: 123126.
141.
ZhangZYangJZhouQ, et al.The cGAS−STING-mediated ROS and ferroptosis are involved in manganese neurotoxicity. J Environ Sci2025; 152: 71–86.
142.
ZhangXLiuJWangH. The cGAS-STING-autophagy pathway: novel perspectives in neurotoxicity induced by manganese exposure. Environ Pollut2022; 315: 120412.
143.
WangQGaoYLiQ, et al.Enhancing dendritic cell activation through manganese-coated nanovaccine targeting the cGAS-STING pathway. Int J Nanomed2024; 19: 263–280.
144.
ZhangXTangDXiaoH, et al.Activating the cGAS-STING pathway by manganese-based nanoparticles combined with platinum-based nanoparticles for enhanced ovarian cancer immunotherapy. ACS Nano2025; 19(4): 4346–4365.
145.
CaiLWangYChenY, et al.Manganese (II) complexes stimulate antitumor immunity via aggravating DNA damage and activating the cGAS-STING pathway. Chem Sci2023; 14(16): 4375–4389.
146.
WangPWangYLiH, et al.A homologous-targeting cGAS-STING agonist multimodally activates dendritic cells for enhanced cancer immunotherapy. Acta Biomater2024; 177: 400–413.
147.
Mallick GangulyOMoulikS. Interactions of Mn complexes with DNA: the relevance of therapeutic applications towards cancer treatment. Dalton Trans2023; 52(31): 10639–10656.
148.
RittiéLAthanasopoulosTCalero-GarciaM, et al.The landscape of early clinical gene therapies outside of oncology. Mol Ther2019; 27(10): 1706–1717.
149.
ShepelevMVKalinichenkoSVVikhrevaPN, et al.Selection of microRNA for providing tumor specificity of transgene expression in cancer gene therapy. Mol Biol2016; 50(2): 327–335.
150.
TeoPYChengWHedrickJL, et al.Co-delivery of drugs and plasmid DNA for cancer therapy. Adv Drug Deliv Rev2016; 98: 41–63.
151.
HaoKGuoZLinL, et al.Covalent organic framework nanoparticles for anti-tumor gene therapy. Sci China Chem2021; 64(7): 1235–1241.
152.
LinGReviaRAZhangM. Inorganic nanomaterial‐mediated gene therapy in combination with other antitumor treatment modalities. Adv Funct Mater2021; 31(5): 2007096.
153.
KumarPTomarSKumarK, et al.Transition metal complexes as self-activating chemical nucleases: proficient DNA cleavage without any exogenous redox agents. Dalton Trans2023; 52(21): 6961–6977.
154.
LiSZhangCXuX, et al.Metal-based biomaterials for cancer gene therapy. Coord Chem Rev2025; 538: 216720.
155.
JiangYFanMYangZ, et al.Recent advances in nanotechnology approaches for non-viral gene therapy. Biomater Sci2022; 10(24): 6862–6892.
156.
JiangRLiLLiM. Biomimetic construction of degradable DNAzyme-loaded nanocapsules for self-sufficient gene therapy of pulmonary metastatic breast cancer. ACS Nano2023; 17(21): 22129–22144.
157.
WuJChenJFengY, et al.Tumor microenvironment as the “regulator” and “target” for gene therapy. J Gene Med2019; 21(7): e3088.
158.
AlAliAAlkanadMAlkanadK, et al.A comprehensive review on anti-inflammatory, antibacterial, anticancer and antifungal properties of several bivalent transition metal complexes. Bioorg Chem2025; 160: 108422.
159.
WangZLiuXDuanY, et al.Infection microenvironment-related antibacterial nanotherapeutic strategies. Biomaterials2022; 280: 121249.
160.
MahmoodAMunirTRasulA, et al.Polyethylene glycol and chitosan functionalized manganese oxide nanoparticles for antimicrobial and anticancer activities. J Colloid Interface Sci2023; 648: 907–915.
161.
RameshPRajendranA. Green synthesis of manganese dioxide nanoparticles: photocatalytic and antimicrobial investigations. Int J Environ Anal Chem2023; 104(19): 8464–8476.
162.
QiuLDiaoZCaiX, et al.Manganese-based nanoenzymes: from catalytic chemistry to design principle and antitumor/antibacterial therapy. Nanoscale2025; 17(14): 8301–8315.
163.
ChuZZhengWFuW, et al.Implanted microneedles loaded with sparfloxacin and zinc‐manganese sulfide nanoparticles activates immunity for postoperative triple‐negative breast cancer to prevent recurrence and metastasis. Adv Sci2025; 12(16): 2416270.
164.
LiuWSunYZhouB, et al.Near-infrared light triggered upconversion nanocomposites with multifunction of enhanced antimicrobial photodynamic therapy and gas therapy for inflammation regulation. J Colloid Interface Sci2024; 663: 834–846.
165.
WangCXiaoYZhuW, et al.Photosensitizer-modified MnO2 nanoparticles to enhance photodynamic treatment of abscesses and boost immune protection for treated mice. Small2020; 16(28): e2000589.
166.
XuWQingXLiuS, et al.Manganese oxide nanomaterials for bacterial infection detection and therapy. J Mater Chem B2022; 10(9): 1343–1358.
167.
KumariSAdvaniDSharmaS, et al.Combinatorial therapy in tumor microenvironment: where do we stand?Biochim Biophys Acta Rev Cancer2021; 1876(2): 188585.
168.
Bayat MokhtariRHomayouniTSBaluchN, et al.Combination therapy in combating cancer. Oncotarget2017; 8(23): 38022–38043.
169.
NguyenATShiaoSLMcArthurHL. Advances in combining radiation and immunotherapy in breast cancer. Clin Breast Cancer2021; 21(2): 143–152.
