Broaden sources and reduce expenditure: Tumor-specific transformable oxidative stress nanoamplifier enabling economized photodynamic therapy for reinforced oxidation therapy

Xu, Xiaoyu; Huang, Binyao; Zeng, Zishan; Chen, Jie; Huang, Zeqian; Guan, Zilin; Chen, Meixu; Huang, Yanjuan; Zhao, Chunshun

doi:10.7150/thno.49731

Cited by 25 publications

(15 citation statements)

References 56 publications

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“…Generally, light source, PSs and O 2 are the three necessary components of PDT. With the continuous development of PSs and optical fiber-guided laser transmission systems, PDT has evolved from theoretical research to clinical research and expanded to imaging and treatment of various cancer and non-cancer diseases 11 - 15 . However, like other therapies, the breadth and depth of PDT's efficacy have not been fully realized due to the limitations such as light penetration depth, inefficient PSs, targeted distribution, and tumor hypoxia 16 - 20 .…”

Section: Introductionmentioning

confidence: 99%

Recent advances in innovative strategies for enhanced cancer photodynamic therapy

et al. 2021

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Photodynamic therapy (PDT), a non-invasive therapeutic modality, has received increasing attention owing to its high selectivity and limited side effects. Although significant clinical research progress has been made in PDT, the breadth and depth of its clinical application have not been fully realized due to the limitations such as inadequate light penetration depth, non-targeting photosensitizers (PSs), and tumor hypoxia. Consequently, numerous investigations put their emphasis on innovative strategies to overcome the aforementioned limitations and enhance the therapeutic effect of PDT. Herein, up-to-date advances in these innovative methods for PDT are summarized by introducing the design of PS systems, their working mechanisms and application examples. In addition, current challenges of these innovative strategies for clinical application, and future perspectives on further improvement of PDT are also discussed.

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Section: Introductionmentioning

confidence: 99%

Recent advances in innovative strategies for enhanced cancer photodynamic therapy

et al. 2021

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“…And studies have shown that ALA is an extremely powerful drug for PDT [ 24 – 26 ]. In the heme biosynthesis pathway, ALA is a natural precursor of protoporphyrin IX (PpIX), a commonly used photosensitizer in clinical PDT [ 27 ]. Abundant mitochondria are necessary for the conversion of ALA to PpIX.…”

Section: Introductionmentioning

confidence: 99%

Minimizing adverse effects of Cerenkov radiation induced photodynamic therapy with transformable photosensitizer-loaded nanovesicles

et al. 2022

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Background Photodynamic therapy (PDT) is a promising antitumor strategy with fewer adverse effects and higher selectivity than conventional therapies. Recently, a series of reports have suggested that PDT induced by Cerenkov radiation (CR) (CR-PDT) has deeper tissue penetration than traditional PDT; however, the strategy of coupling radionuclides with photosensitizers may cause severe side effects. Methods We designed tumor-targeting nanoparticles (131I-EM@ALA) by loading 5-aminolevulinic acid (ALA) into an 131I-labeled exosome mimetic (EM) to achieve combined antitumor therapy. In addition to playing a radiotherapeutic role, 131I served as an internal light source for the Cerenkov radiation (CR). Results The drug-loaded nanoparticles effectively targeted tumors as confirmed by confocal imaging, flow cytometry, and small animal fluorescence imaging. In vitro and in vivo experiments demonstrated that 131I-EM@ALA produced a promising antitumor effect through the synergy of radiotherapy and CR-PDT. The nanoparticles killed tumor cells by inducing DNA damage and activating the lysosome-mitochondrial pathways. No obvious abnormalities in the hematology analyses, blood biochemistry, or histological examinations were observed during the treatment. Conclusions We successfully engineered a nanocarrier coloaded with the radionuclide 131I and a photosensitizer precursor for combined radiotherapy and PDT for the treatment of breast cancer. Graphical Abstract

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“…Tumor cells modify their iron metabolism to maximize absorption and minimize outflow, increasing labile iron ( Duan et al, 2019 ). The abnormal metabolism and proliferation of cancer cells require a high level of iron and, consequently, tumor tissues contain a higher amount of iron than normal tissues ( Xu et al, 2020 ). There is also evidence that an abnormal iron metabolism may lead to tumor initiation, proliferation, and metastasis ( Raggi et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

ATP6AP1 is a potential prognostic biomarker and is associated with iron metabolism in breast cancer

et al. 2022

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Cancer occurrence and progression may be facilitated by aberrant expression of ATPase H+ transporting accessory protein 1 (ATP6AP1). However, the clinical relevance of ATP6AP1 in breast cancer remains unclear. In this study, we investigated the association between ATP6AP1 and breast cancer. Data collected from patients with breast cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were used in this study. To determine the relationship between ATP6AP1 and breast cancer survival rates, Kaplan-Meier analysis was used. To determine the prognostic value of ATP6AP1, a receiver operating characteristic (ROC) curve was constructed. To identify the major pathways involving ATP6AP1, we performed functional enrichment analysis using gene set enrichment analysis (GSEA). We analyzed the association between ATP6AP1 expression and tumor immunity using the ESTIMATE algorithm and single-sample GSEA (ssGSEA). A nomogram based on a Cox regression analysis was constructed to predict the impact of ATP6AP1 on prognosis. ATP6AP1 expression was significantly upregulated in breast cancer tissues. Moreover, patients with elevated ATP6AP1 expression had shorter total survival rates than those with lower expression levels (p = 0.032). The area under the receiver operating characteristic curve for ATP6AP1 was 0.939. Gene set enrichment analysis revealed that reaction iron uptake and transport, proteasome degradation, glutathione metabolism, and pyruvate metabolism were enriched in the ATP6AP1 high expression phenotype. The relationship between immune infiltration cells and ATP6AP1 expression, including macrophages, B cells, dendritic cells, cytotoxic cells, NK cells, and T cells, was found to be negative, suggesting that ATP6AP1 overexpression results in immunosuppression. Based on the Cox regression analyses, the calibration plot of the nomogram demonstrated effective performance in predicting breast cancer patients. ATP6AP1 may facilitate breast cancer progression by inhibiting antitumor immunity and promoting iron metabolism and may be a biomarker for breast cancer prognosis.

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Broaden sources and reduce expenditure: Tumor-specific transformable oxidative stress nanoamplifier enabling economized photodynamic therapy for reinforced oxidation therapy

Cited by 25 publications

References 56 publications

Recent advances in innovative strategies for enhanced cancer photodynamic therapy

Recent advances in innovative strategies for enhanced cancer photodynamic therapy

Minimizing adverse effects of Cerenkov radiation induced photodynamic therapy with transformable photosensitizer-loaded nanovesicles

ATP6AP1 is a potential prognostic biomarker and is associated with iron metabolism in breast cancer

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