Reprogramming of the tumor microenvironment using a PCN-224@IrNCs/<scp>d</scp>-Arg nanoplatform for the synergistic PDT, NO, and radiosensitization therapy of breast cancer and improving anti-tumor immunity

Zou, Yi-Ming; Li, Rong-Tian; Yu, Lei; Huang, Ting; Peng, Jian; Meng, Wei; Sun, Bin; Zhang, Wen-Hua; Jiang, Zhi-Hong; Chen, Jun; Chen, Jin-Xiang

doi:10.1039/d3nr01050c

Cited by 7 publications

(4 citation statements)

References 53 publications

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“…Fe-TMPP is supported by a porphyrin-based ligand, which is often used for type II PDT of cancer [ 3 , 7 , 37 ]. We employed diphenylisobenzofuran (DPBF) as a probe to compare the singlet oxygen’s ( 1 O 2 ) generating capacity with that of TMPP-F127 (H 2 TMPP encapsuled by Pluronic F-127, Figure S13 ) [ 38 ], using blank DPBF as a control [ 39 , 40 ].…”

Section: Resultsmentioning

confidence: 99%

“…Molecules 2024, 29, x FOR PEER REVIEW 6 of 14 to a strong four-line signal with a 1:2:2:1 peak-to-peak intensity pattern, characteristic of the generation of •OH from H2O2 [4,5]. Fe-TMPP is supported by a porphyrin-based ligand, which is often used for type II PDT of cancer [3,7,37]. We employed diphenylisobenzofuran (DPBF) as a probe to compare the singlet oxygenʹs ( 1 O2) generating capacity with that of TMPP-F127 (H2TMPP encapsuled by Pluronic F-127, Figure S13) [38], using blank DPBF as a control [39,40].…”

Section: In Vitro Ros Detection and Cytotoxicity Assaymentioning

confidence: 99%

“…Materials designed to target the unique features of the tumor microenvironment (TME), such as the over-expression of H 2 O 2 and glutathione (GSH), weak acidity, hypoxia, and immunosuppression, are attracting intensive interest in the field of nanomedicine [ 1 , 2 , 3 , 4 , 5 , 6 ]. Materials that are responsive exclusively to the TME imply low systemic toxicity and thus fewer side effects.…”

Section: Introductionmentioning

confidence: 99%

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[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis

Wang,

Feng,

Zeng

et al. 2024

Molecules

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Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098−3.97 μM (0.066−2.68 μg mL−1), comparable to the best-reported medicines. Fe-TMPP can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.

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Section: Resultsmentioning

confidence: 99%

Section: In Vitro Ros Detection and Cytotoxicity Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis

Wang,

Feng,

Zeng

et al. 2024

Molecules

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“…33 These DAMPs mediate the activation of dendritic cells (DCs), followed by subsequent DC maturation for antigen presentation and promotion of cytotoxic T lymphocyte (CTL)-mediated cancer cell death. 34…”

Section: Introductionmentioning

confidence: 99%

Biotin-decorated hollow gold nanoshells for dual-modal imaging-guided NIR-II photothermal and radiosensitizing therapy toward breast cancer

Chen,

Meng,

Chen

et al. 2023

J. Mater. Chem. B

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A Self‐Catalytic NO/O₂ Gas‐Releasing Nanozyme for Radiotherapy Sensitization through Vascular Normalization and Hypoxia Relief

Wang,

Cheng,

Wang

et al. 2024

Advanced Materials

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Radiotherapy (RT), essential for treating various cancers, faces challenges from tumor hypoxia, which induces radioresistance. A tumor‐targeted “prosthetic‐Arginine” coassembled nanozyme system, engineered to catalytically generate nitric oxide (NO) and oxygen (O2) in the tumor microenvironment (TME), overcoming hypoxia and enhancing radiosensitivity is presented. This system integrates the prosthetic heme of nitric oxide synthase (NOS) and catalase (CAT) with NO‐donating Fmoc‐protected Arginine and Ru3+ ions, creating HRRu nanozymes that merge NOS and CAT functionalities. Surface modification with human heavy chain ferritin (HFn) improves the targeting ability of nanozymes (HRRu‐HFn) to tumor tissues. In the TME, strategic arginine incorporation within the nanozyme allows autonomous O2 and NO release, triggered by endogenous hydrogen peroxide, elevating NO and O2 levels to normalize vasculature and improve blood perfusion, thus mitigating hypoxia. Employing the intrinsic O2‐transporting ability of heme, HRRu‐HFn nanozymes also deliver O2 directly to the tumor site. Utilizing esophageal squamous cell carcinoma as a tumor model, the studies reveal that the synergistic functions of NO and O2 production, alongside targeted delivery, enable the HRRu‐HFn nanozymes to combat tumor hypoxia and potentiate radiotherapy. This HRRu‐HFn nanozyme based approach holds the potential to reduce the radiation dose required and minimize side effects associated with conventional radiotherapy.

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Reprogramming of the tumor microenvironment using a PCN-224@IrNCs/d-Arg nanoplatform for the synergistic PDT, NO, and radiosensitization therapy of breast cancer and improving anti-tumor immunity

Abstract: The low X-ray attenuation coefficient of tumor soft tissue and the hypoxic tumor microenvironment (TME) during radiation therapy (RT) of breast cancer results in RT resistance and thus reduced therapeutic...

Cited by 7 publications

References 53 publications

[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis

[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis

Biotin-decorated hollow gold nanoshells for dual-modal imaging-guided NIR-II photothermal and radiosensitizing therapy toward breast cancer

A Self‐Catalytic NO/O₂ Gas‐Releasing Nanozyme for Radiotherapy Sensitization through Vascular Normalization and Hypoxia Relief

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Reprogramming of the tumor microenvironment using a PCN-224@IrNCs/d-Arg nanoplatform for the synergistic PDT, NO, and radiosensitization therapy of breast cancer and improving anti-tumor immunity

Abstract: The low X-ray attenuation coefficient of tumor soft tissue and the hypoxic tumor microenvironment (TME) during radiation therapy (RT) of breast cancer results in RT resistance and thus reduced therapeutic...

Cited by 7 publications

References 53 publications

[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis

[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis

Biotin-decorated hollow gold nanoshells for dual-modal imaging-guided NIR-II photothermal and radiosensitizing therapy toward breast cancer

A Self‐Catalytic NO/O2 Gas‐Releasing Nanozyme for Radiotherapy Sensitization through Vascular Normalization and Hypoxia Relief

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A Self‐Catalytic NO/O₂ Gas‐Releasing Nanozyme for Radiotherapy Sensitization through Vascular Normalization and Hypoxia Relief