Cascaded amplification of intracellular oxidative stress and reversion of multidrug resistance by nitric oxide prodrug based-supramolecular hydrogel for synergistic cancer chemotherapy

Zhang, Jimin; Deng, Meigui; Shi, Xiaoguang; Zhang, Chuangnian; Qu, Xiongwei; Hu, Xiuli; Huang, Pingsheng

doi:10.1016/j.bioactmat.2021.03.005

Cited by 8 publications

(9 citation statements)

References 64 publications

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“…NO release systems formed by NO donors or precursors covalently and non-covalently bound to a hydrogel matrix are summarized in Table 3 and Table 4 . Most NO-releasing hydrogels were designed and tested for wound healing purposes, but due to the many properties of NO, other applications (i.e., antibacterial activity [ 41 , 90 , 91 , 92 ], vasodilation [ 39 , 93 , 94 ], biomedical applications or tissue engineering [ 65 , 92 , 95 ], anticancer activity [ 90 , 96 , 97 ]) were also targeted. NO is used in anticancer therapeutics as a way to make tumorous cells more susceptible to chemotherapeutic drugs.…”

Section: No-releasing Hydrogel-based Systemsmentioning

confidence: 99%

“…A mixed release profile is reported for few systems [ 41 , 77 , 95 , 125 ]. Controlled and paced NO release has been reported for the systems reliant on enzymatic catalysis [ 65 , 96 , 126 , 127 ]. Enzymatic sensitivity allows greater control over NO delivery and release rate, as the latter is dictated by enzyme kinetics.…”

Section: No-releasing Hydrogel-based Systemsmentioning

confidence: 99%

“…NO release occurs after the protecting molecule (e.g., galactose) is modified by the enzyme (i.e., glycosidase enzyme for galactose substrate), deprotecting the NO donor, which then decomposes. Complex and specific molecules can also donate NO upon direct modification by enzymes [ 96 ]. Moreover, enzyme-responsive delivery systems hold their cargo in the absence of enzyme independently of the medium, therefore eliminating spontaneous release.…”

Section: No-releasing Hydrogel-based Systemsmentioning

confidence: 99%

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Recent Advances in Hydrogel-Mediated Nitric Oxide Delivery Systems Targeted for Wound Healing Applications

2022

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Despite the noticeable evolution in wound treatment over the centuries, a functional material that promotes correct and swift wound healing is important, considering the relative weight of chronic wounds in healthcare. Difficult to heal in a fashionable time, chronic wounds are more prone to infections and complications thereof. Nitric oxide (NO) has been explored for wound healing applications due to its appealing properties, which in the wound healing context include vasodilation, angiogenesis promotion, cell proliferation, and antimicrobial activity. NO delivery is facilitated by molecules that release NO when prompted, whose stability is ensured using carriers. Hydrogels, popular materials for wound dressings, have been studied as scaffolds for NO storage and delivery, showing promising results such as enhanced wound healing, controlled and sustained NO release, and bactericidal properties. Systems reported so far regarding NO delivery by hydrogels are reviewed.

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Section: No-releasing Hydrogel-based Systemsmentioning

confidence: 99%

Section: No-releasing Hydrogel-based Systemsmentioning

confidence: 99%

Section: No-releasing Hydrogel-based Systemsmentioning

confidence: 99%

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Recent Advances in Hydrogel-Mediated Nitric Oxide Delivery Systems Targeted for Wound Healing Applications

2022

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“…[34][35][36] Therefore, it is reasonable to suppose that a combination of NO therapy with IDO inhibition may improve the antitumor outcome. So far, although NO therapy has been proven to synergize with other therapeutic approaches, such as chemotherapy and photothermal therapy, [37,38] the potential to synergize with IDO inhibition for effective antitumor immunotherapy has not been explored yet.…”

Section: Introductionmentioning

confidence: 99%

GSH‐Responsive Metal–Organic Framework for Intratumoral Release of NO and IDO Inhibitor to Enhance Antitumor Immunotherapy

Xiao

et al. 2022

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renal cell carcinoma (RCC), [2] and nonsmall cell lung carcinoma (NSCLC). [3] Through active or passive means, tumor immunotherapy induces the body to produce a tumor-specific immune response which suppresses the tumor progression and prevents the tumor recurrence or metastasis. [4][5][6] Strategies reported for tumor immunotherapy so far mainly involved immune checkpoint blockade (ICB), [7] adoptive cell transfer therapy (ACT), [8] tumor-specific vaccines, [9] and application of small molecular immunemodulating drugs. [10] However, most immunotherapy methods often encounter the great challenge of not being effective enough for many tumors of which a large amount do not respond in the clinic, [11,12] requiring advanced tumor immunotherapy methods to be developed.Among various tumor immunotherapy strategies, inhibition of the indoleamine-2,3-dioxygenase (IDO) is drawing great attention at present because of its critical role in mediating tumor immune evasion, and some inspiring studies were reported. [13][14][15] Admittedly, IDO catalyzes the degradation of amino acid l-tryptophan (Trp) into the metabolite l-kynurenine (Kyn), which suppresses cytotoxic T lymphocytes (CTL) and activates regulatory T (Treg) cells. [16,17] The strong immunomodulatory functions of IDO can be attributed Immunotherapy brings great benefits for tumor therapy in clinical treatments but encounters the severe challenge of low response rate mainly because of the immunosuppressive tumor microenvironment. Multifunctional nanoplatforms integrating effective drug delivery and medical imaging offer tremendous potential for cancer treatment, which may play a critical role in combinational immunotherapy to overcome the immunosuppressive microenvironment for efficient tumor therapy. Here, a nanodrug (BMS-SNAP-MOF) is prepared using glutathione (GSH)-sensitive metal-organic framework (MOF) to encapsulate an immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) inhibitor BMS-986205, and the nitric oxide (NO) donor s-nitrosothiol groups. The high T1 relaxivity allows magnetic resonance imaging to monitor nanodrug distribution in vivo. After the nanodrug accumulation in tumor tissue via the EPR effect and subsequent internalization into tumor cells, the enriched GSH therein triggers cascade reactions with MOF, which disassembles the nanodrug to rapidly release the IDO-inhibitory BMS-986205 and produces abundant NO. Consequently, the IDO inhibitor and NO synergistically modulate the immunosuppressive tumor microenvironment with increase CD8 + T cells and reduce Treg cells to result in highly effective immunotherapy.In an animal study, treatment using this theranostic nanodrug achieves obvious regressions of both primary and distant 4T1 tumors, highlighting its application potential in advanced tumor immunotherapy.

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“…For example, NO has been demonstrated to strengthen the enhanced permeability and retention (EPR) effect by vasodilation, which could enhance the accumulation efficiency of nanomedicines [21]. Moreover, NO, CO and sulfur dioxide (SO 2 ) could enhance the effect of chemotherapy by overcoming the multidrug resistance (MDR) of tumor cells [22][23][24]. Furthermore, hydrogen (H 2 ) has been found to kill tumor cells and protect normal cells at the same time at proper concentrations [25].…”

Section: Introductionmentioning

confidence: 99%

Stimuli Responsive Nitric Oxide-Based Nanomedicine for Synergistic Therapy

et al. 2021

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Gas therapy has received widespread attention from the medical community as an emerging and promising therapeutic approach to cancer treatment. Among all gas molecules, nitric oxide (NO) was the first one to be applied in the biomedical field for its intriguing properties and unique anti-tumor mechanisms which have become a research hotspot in recent years. Despite the great progress of NO in cancer therapy, the non-specific distribution of NO in vivo and its side effects on normal tissue at high concentrations have impaired its clinical application. Therefore, it is important to develop facile NO-based nanomedicines to achieve the on-demand release of NO in tumor tissue while avoiding the leakage of NO in normal tissue, which could enhance therapeutic efficacy and reduce side effects at the same time. In recent years, numerous studies have reported the design and development of NO-based nanomedicines which were triggered by exogenous stimulus (light, ultrasound, X-ray) or tumor endogenous signals (glutathione, weak acid, glucose). In this review, we summarized the design principles and release behaviors of NO-based nanomedicines upon various stimuli and their applications in synergistic cancer therapy. We also discuss the anti-tumor mechanisms of NO-based nanomedicines in vivo for enhanced cancer therapy. Moreover, we discuss the existing challenges and further perspectives in this field in the aim of furthering its development.

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Cascaded amplification of intracellular oxidative stress and reversion of multidrug resistance by nitric oxide prodrug based-supramolecular hydrogel for synergistic cancer chemotherapy

Abstract: Graphical abstract

Cited by 8 publications

References 64 publications

Recent Advances in Hydrogel-Mediated Nitric Oxide Delivery Systems Targeted for Wound Healing Applications

Recent Advances in Hydrogel-Mediated Nitric Oxide Delivery Systems Targeted for Wound Healing Applications

GSH‐Responsive Metal–Organic Framework for Intratumoral Release of NO and IDO Inhibitor to Enhance Antitumor Immunotherapy

Stimuli Responsive Nitric Oxide-Based Nanomedicine for Synergistic Therapy

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