ROS-Responsive and pH-Sensitive Aminothiols Dual-Prodrug for Radiation Enteritis

Chen, Yuanfang; Yang, Y.B.; Tang, Haikang; Zhang, Ziqi; Zhou, Xiaoliang; Xu, Wenqing

doi:10.3390/antiox11112145

Cited by 4 publications

(3 citation statements)

References 39 publications

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“…Notably, Inu alone displayed no ABTS and DPPH radical-scavenging activity (Figure 3A,B). Since TK has been extensively reported on for its role in scavenging free radicals [40], we speculated the observed improvement results from the synergistic effect between TK and Cur. Hydroxyl (OH•) radicals are the most representative ROS produced by ionizing radiation.…”

Section: In Vitro Antioxidant Ability Of Ctimentioning

confidence: 93%

Oral Curcumin–Thioketal–Inulin Conjugate Micelles against Radiation–Induced Enteritis

Shen,

Jiao,

Yuan

et al. 2024

Antioxidants

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Radiation–induced enteritis is an unavoidable complication associated with pelvic tumor radiotherapy, significantly influencing the prognosis of cancer patients. The limited availability of commercial gastrointestinal radioprotectors in clinical settings poses a substantial challenge in preventing radiation enteritis. Despite the inherent radioprotective characteristics of Cur in vitro, its poor solubility in water, instability, and low bioavailability lead to inferior therapeutic effects in vivo. Herein, we developed novel ROS-responsive micelles (CTI) from inulin and curcumin, aimed at mitigating radiation enteritis. CTI micelles had excellent solubility and stability. Importantly, CTI improved the cytotoxicity and bioavailability of curcumin, thereby showing enhanced effectiveness in neutralizing ROS induced by radiation, safeguarding against DNA damage, and reducing radiation-induced cellular mortality. Moreover, in a radiation enteritis mice model, CTI not only alleviated severe radiation-induced intestinal injury but also improved redox-related indicators and reduced inflammatory cytokine expression. Furthermore, CTI effectively increased gut microbiota abundance and maintained gut homeostasis. In conclusion, CTI could be a promising candidate for the clinical management of radiation enteritis. Our study provides a new perspective for radioprotection using natural antioxidants.

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Section: In Vitro Antioxidant Ability Of Ctimentioning

confidence: 93%

Oral Curcumin–Thioketal–Inulin Conjugate Micelles against Radiation–Induced Enteritis

Shen,

Jiao,

Yuan

et al. 2024

Antioxidants

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“…Vectors based on pH/hypoxia dual response are rarely used in the delivery of RNA. However, they are more studied in the drug release of some tumors and various inflammations such as arthritis and colitis. , Although dual-response delivery vectors have been constructed to deliver interfering RNAs and drugs, RNA delivery vectors based on three or more stimuli still need to be discovered. Nevertheless, the field still shows broad promise based on the available research data and technological developments.…”

Section: Tme-based Stimuli-responsive Rna Delivery Systemsmentioning

confidence: 99%

Tumor Microenvironment Responsive RNA Drug Delivery Systems: Intelligent Platforms for Sophisticated Release

Wang,

Zhang,

Lai

et al. 2024

Mol. Pharmaceutics

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Cancer is a significant health concern, increasingly showing insensitivity to traditional treatments, highlighting the urgent need for safer and more practical treatment options. Ribonucleic acid (RNA) gene therapy drugs have demonstrated promising potential in preclinical and clinical trials for antitumor therapy by regulating tumor-related gene expression. However, RNA's poor membrane permeability and stability restrict its effectiveness in entering and being utilized in cells. An appropriate delivery system is crucial for achieving targeted tumor effects. The tumor microenvironment (TME), characterized by acidity, hypoxia, enzyme overexpression, elevated glutathione (GSH) concentration, and excessive reactive oxygen species (ROS), is essential for tumor survival. Furthermore, these distinctive features can also be harnessed to develop intelligent drug delivery systems. Various nanocarriers that respond to the TME have been designed for RNA drug delivery, showing the advantages of tumor targeting and low toxicity. This Review discusses the abnormal changes of components in TME, therapeutic RNAs' roles, underlying mechanisms, and the latest developments in utilizing vectors that respond to microenvironments for treating tumors. We hope it provides insight into creating and optimizing RNA delivery vectors to improve their effectiveness.

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“…Various prodrug types and their corresponding activation mechanisms have been reported, e.g., overexpressed enzymes, pH changes, UV/NIR irradiation, activation by electromagnetic fields, photo-induced activation, and elevated reactive oxygen and nitrogen species (RONS) levels [ 1 , 2 ]. RONS-responsive prodrugs are currently receiving attention as efficient drug delivery tools [ 3 , 4 ]. These prodrugs often possess active functional groups, such as –OH, −NH 2 [ 5 ], or –CONHOH [ 6 ], masked by a protective group that is eventually cleaved off at the target site [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Cold Physical Plasma-Mediated Fenretinide Prodrug Activation Confers Additive Cytotoxicity in Epithelial Cells

et al. 2023

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Cold physical plasma is a partially ionized gas operated at body temperature and utilized for heat-sensitive technical and medical purposes. Physical plasma is a multi-component system consisting of, e.g., reactive species, ions and electrons, electric fields, and UV light. Therefore, cold plasma technology is an interesting tool for introducing biomolecule oxidative modifications. This concept can be extended to anticancer drugs, including prodrugs, which could be activated in situ to enhance local anticancer effects. To this end, we performed a proof-of-concept study on the oxidative prodrug activation of a tailor-made boronic pinacol ester fenretinide treated with the atmospheric pressure argon plasma jet kINPen operated with either argon, argon–hydrogen, or argon–oxygen feed gas. Fenretinide release from the prodrug was triggered via Baeyer–Villiger-type oxidation of the boron–carbon bond based on hydrogen peroxide and peroxynitrite, which were generated by plasma processes and chemical addition using mass spectrometry. Fenretinide activation led to additive cytotoxic effects in three epithelial cell lines in vitro compared to the effects of cold plasma treatment alone regarding metabolic activity reduction and an increase in terminal cell death, suggesting that cold physical plasma-mediated prodrug activation is a new direction for combination cancer treatment studies.

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ROS-Responsive and pH-Sensitive Aminothiols Dual-Prodrug for Radiation Enteritis

Cited by 4 publications

References 39 publications

Oral Curcumin–Thioketal–Inulin Conjugate Micelles against Radiation–Induced Enteritis

Oral Curcumin–Thioketal–Inulin Conjugate Micelles against Radiation–Induced Enteritis

Tumor Microenvironment Responsive RNA Drug Delivery Systems: Intelligent Platforms for Sophisticated Release

Cold Physical Plasma-Mediated Fenretinide Prodrug Activation Confers Additive Cytotoxicity in Epithelial Cells

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