Tumor‐penetrating peptide internalizing RGD enhances radiotherapy efficacy through reducing tumor hypoxia

Meng, Fanyan; Li, Jun; Wei, Jia; Yang, Ju; Zhou, Chong; Yan, Jing; Liu, Baorui

doi:10.1111/cas.15295

Cited by 6 publications

(6 citation statements)

References 45 publications

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“…The following biological processes can affect radiation resistance in both the tumor and the microenvironment around it: changed DNA damage response (DDR) and increased DNA repair; hypoxia; cancer stem cell repopulation; altered cell cycle; inflammation; altered management of oxidative stress; altered mitochondrial function and cellular energetics (3,(16)(17)(18)(19)(20)(21). We previously described the remodeling tumor tissue penetration via tumor-penetrating peptide iRGD enhanced radiation efficacy and summarized the molecular mechanism for this type of peptide: peptide iRGD can reduced hypoxia and enhanced the efficacy of radiation through MRP-1 (7). Notably, LyP-1 also can reduce hypoxia (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In previous work, we described a remodeling tumor tissue penetration via tumor-penetrating peptide internalizing arginine-glycine-aspartic acid RGD (iRGD) enhanced radiation efficacy, and applied the peptide to treat mice with 4T1 tumor ( 7 ). The iRGD contain three independent modules: vascular homing sequence, R/KXXR/K tissue penetration sequence, and protease recognition site ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

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Tumor-penetrating Peptide LyP-1 Enhance Efficacy of Radiotherapy by Reversing Suppressive Immune Microenvironment

Shi,

Chen,

Liu

et al. 2023

Radiation Research

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Radiotherapy has shown remarkable clinical success using high doses of radiation to kill cancer cells and shrink tumors; however, tumor resistance to radiation is still an intractable challenge to enhance radiation damage to tumor tissue. Here, we show a capacity of tumor-penetrating peptide LyP-1 that enhanced the effect of radiation on 4T1 tumor. We injected LyP-1 peptide into the tumor model through the tail vein and irradiated mice subsequently. The radiation treatment combined with LyP-1 exhibited significant regression of the tumor compared to radiation alone or LyP-1 alone. We analyzed the tumor immune microenvironment after treatment, the expression of myeloid-derived suppressor cells (MDSCs) both in the spleen and the tumor were effectively suppressed. Besides, LyP-1 could drive macrophage polarization to the M1 phenotype and regulate its immune function. We also evaluated the safety of this strategy, the results demonstrated that radiation combined with LyP-1 exhibited excellent in vivo safety and tumor suppression. Therefore, LyP-1 can be a promising radiosensitizer candidate to enhance radiation efficacy as well as induce reactivation of the immune system.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tumor-penetrating Peptide LyP-1 Enhance Efficacy of Radiotherapy by Reversing Suppressive Immune Microenvironment

Shi,

Chen,

Liu

et al. 2023

Radiation Research

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“…iRGD was initially used for tumor-specific delivery of small-molecule compounds ( 11 ). Previously, we found in vivo and in vitro experiments that free iRGD can increase the radiosensitivity of breast cancer cells 4T1 via remodeling tumor tissue penetration ( 17 ). However, free iRGD is quickly metabolized by the body’s liver and spleen.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study reported for the first time that the modification of iRGD could improve the cancer-specific lymphocyte infiltration in both mouse models and 3D cancer spheroids ( 16 ). Recently, we demonstrated that iRGD could enhance irradiation efficacy via remodeling tumor tissue penetration ( 17 ). However, the feasibility of employment of iRGD for RBC modification has not been reported yet.…”

Section: Introductionmentioning

confidence: 99%

Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma

Zhou¹,

Liu²,

Meng³

et al. 2022

J Gastrointest Oncol

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Background: Radiation resistance remains the leading cause of radiotherapy (RT) failure. The development of tumor-specific targeted sensitizers is key to overcoming radiation resistance. Our early data showed that cancer cell penetration was simulated by internalizing arginine-glycine-aspartic acid (iRGD), and the irradiation efficacy was improved. The present study aims to design and fabricate iRGD-modified red blood cell (RBCs) for tumor targeting and RT enhancement, and to evaluate its safety and efficacy in vivo.Methods: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-poly ethylene glycol-iRGD (DSPE-PEG-iRGD) was used to modify RBCs by a lipid-insertion method without direct chemical bioconjugation.Fluorescent dyes were used to trace the functional RBCs through confocal microscopy examination. In vitro stability evaluation was performed using cell culture medium incubation for 48 h followed by fluorescence decay assay. Furthermore, a subcutaneous cancer cell mouse model was constructed with MKN-45 cells for target efficacy and RT enhancement evaluation with DSPE-PEG-iRGD-modified RBCs (RBC-iRGD).Results: Successful construction of RBC-iRGD was verified by the presence of the yellow fluorescence, and an approximately 10 8 iRGD molecules were labeled on a single RBC. The final RBC-iRGD showed good stability without any hemolytic effects in the cell culture medium. Moreover, higher fluorescence intensity and decreased liver and spleen accumulation could be observed in RBC-iRGD compared to RBC + iRGD in vivo. The RBC-iRGD exerted enhanced radiosensitivity in subcutaneous gastric tumor mice. Conclusions:The RBC-iRGD exerted good tumor-targeting efficacy and favorable effects for RT enhancement in vivo.

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“…Hypoxia plays a key role in mediating irradiation resistance and iRGD allows the diffusion of oxygen molecules into tumor tissues alleviating hypoxia. 77 The ProteoChip system was used to develop twelve α v β 3 -antagonistic peptides from the hexapeptide library. Interestingly, the two hexapeptides with the highest antiangiogenic and antimetastatic activities contained the Ser–Asp–Val (SDV) and Gly–Asp–Val (GDV) sequences.…”

Section: Types Of Acps and Their Mode Of Actionmentioning

confidence: 99%

Peptide therapeutics in the management of metastatic cancers

2022

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Tumor‐penetrating peptide internalizing RGD enhances radiotherapy efficacy through reducing tumor hypoxia

Cited by 6 publications

References 45 publications

Tumor-penetrating Peptide LyP-1 Enhance Efficacy of Radiotherapy by Reversing Suppressive Immune Microenvironment

Tumor-penetrating Peptide LyP-1 Enhance Efficacy of Radiotherapy by Reversing Suppressive Immune Microenvironment

Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma

Peptide therapeutics in the management of metastatic cancers

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