Promoting Reactive Oxygen Species Generation: A Key Strategy in Nanosensitizer-Mediated Radiotherapy

Jia, Shichong; Ge, Shengfang; Fan, Xianqun; Leong, Kam W.; Ruan, Jing

doi:10.2217/nnm-2020-0448

Cited by 38 publications

(25 citation statements)

References 122 publications

(126 reference statements)

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“…The literature identifies many cell death or anti-survival modalities, and these include accidental cell death, anoikis, autophagy-dependent cell death, autosis, efferocytosis, entotic cell death, ferroptosis, immunogenic cell death, lysosome-dependent cell death, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, NETotic cell death, parthanatos, pyroptosis, mitotic catastrophe and mitotic death, extrinsic apoptosis, intrinsic apoptosis, and methuosis [ 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 ]. With the availability of a vast array of clinical and experimental synthetic and natural compounds and drug delivery modes, their rational combination has the potential to target a multitude of cell death mechanisms [ 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 , 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 ] to bring about the death of all cancer cells including cancer stem cells, dormant cells, circulating cancer cells, micro-metastases, and DTP and muti-drug resistant malignant cells ( Figure 6 ).…”

Section: Future Landscapementioning

confidence: 99%

A Tale of Two Cancers: A Current Concise Overview of Breast and Prostate Cancer

Silva

Alcorn

2022

Cancers

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Cancer is a global issue, and it is expected to have a major impact on our continuing global health crisis. As populations age, we see an increased incidence in cancer rates, but considerable variation is observed in survival rates across different geographical regions and cancer types. Both breast and prostate cancer are leading causes of morbidity and mortality worldwide. Although cancer statistics indicate improvements in some areas of breast and prostate cancer prevention, diagnosis, and treatment, such statistics clearly convey the need for improvements in our understanding of the disease, risk factors, and interventions to improve life span and quality of life for all patients, and hopefully to effect a cure for people living in developed and developing countries. This concise review compiles the current information on statistics, pathophysiology, risk factors, and treatments associated with breast and prostate cancer.

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Section: Future Landscapementioning

confidence: 99%

A Tale of Two Cancers: A Current Concise Overview of Breast and Prostate Cancer

Silva

Alcorn

2022

Cancers

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“…These activated immune cells generate pro-inflammatory cytokines (e.g. TNF-α, IL-1β, IL-6, IL-12) ( 14 , 23 , 24 ), chemokines and growth factors leading to a sustained inflammatory response ( 22 , 25 ).…”

Section: Radiotherapy and The Anti-tumour Immune Responsementioning

confidence: 99%

Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy

et al. 2022

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Radiotherapy is one of the most effective and frequently used treatments for a wide range of cancers. In addition to its direct anti-cancer cytotoxic effects, ionising radiation can augment the anti-tumour immune response by triggering pro-inflammatory signals, DNA damage-induced immunogenic cell death and innate immune activation. Anti-tumour innate immunity can result from recruitment and stimulation of dendritic cells (DCs) which leads to tumour-specific adaptive T-cell priming and immunostimulatory cell infiltration. Conversely, radiotherapy can also induce immunosuppressive and anti-inflammatory mediators that can confer radioresistance. Targeting the DNA damage response (DDR) concomitantly with radiotherapy is an attractive strategy for overcoming radioresistance, both by enhancing the radiosensitivity of tumour relative to normal tissues, and tipping the scales in favour of an immunostimulatory tumour microenvironment. This two-pronged approach exploits genomic instability to circumvent immune evasion, targeting both hallmarks of cancer. In this review, we describe targetable DDR proteins (PARP (poly[ADP-ribose] polymerase); ATM/ATR (ataxia–telangiectasia mutated and Rad3-related), DNA-PKcs (DNA-dependent protein kinase, catalytic subunit) and Wee1 (Wee1-like protein kinase) and their potential intersections with druggable immunomodulatory signalling pathways, including nucleic acid-sensing mechanisms (Toll-like receptors (TLR); cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) and retinoic acid-inducible gene-I (RIG-I)-like receptors), and how these might be exploited to enhance radiation therapy. We summarise current preclinical advances, recent and ongoing clinical trials and the challenges of therapeutic combinations with existing treatments such as immune checkpoint inhibitors.

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“…Tumor re‐oxygenation was usually achieved by constructing oxygen carriers or oxygen generators to alleviate tumor hypoxia [ 12b,13 ] and improve reactive oxygen species (ROS) production in tumor cells. [ 12b,14 ] Taking advantage of the hypoxic microenvironment was mainly achieved through the introduction of oxygen‐independent radio‐sensitizing molecules, such as electron‐affinic nitroaromatic or nitroheterocyclic derivatives, to enhance the therapeutic sensitivity of tumor cells. [ 15 ] In the latter scenario, some bio‐reductive anticancer drugs with hypoxia‐activated cytotoxicity, such as tirapazamine (TPZ), benoxanthrene dihydrochloride, and mitomycin C have been proved to efficiently utilize the hypoxic environment to sensitize RT.…”

Section: Introductionmentioning

confidence: 99%

A Multimodal Therapeutic Nanoplatform Overcoming Tumor Hypoxia Heterogeneity for Improved Tumor Chemoradiotherapy

Zhang

et al. 2022

Adv Funct Materials

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The hypoxic nature of solid tumors limits the efficacy of radiotherapy (RT) and leads to radiation resistance. Hypoxic radiosensitizers can enhance tumor radiosensitivity by mimicking the effects of oxygen, but their efficacy has been limited by the heterogeneous oxygen distribution in tumor tissue. Herein, a multimodal therapeutic nanoplatform fabricated by co-encapsulation of chlorin e6 and tirapazamine (TPZ) with an amphiphilic polymeric conjugate of cisplatin (CDDP) and metronidazole is reported. This platform could kill the tumor periphery cells by the deeply penetrated oxygen-consuming sonodynamic therapy and unify the heterogeneously hypoxic context simultaneously, which then actuate the release and activation of the loaded TPZ. TPZ could further sensitize RT along with CDDP and metronidazole residues under the resultant hypoxic condition, which significantly decreases the radiation dosage required to cause massive cell damage. Except for the significantly suppressed tumor growth and metastasis caused by the multimodal therapeutic nanoplatform, its hypoxia-directed feature also endows it with excellent safety.

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Promoting Reactive Oxygen Species Generation: A Key Strategy in Nanosensitizer-Mediated Radiotherapy

Cited by 38 publications

References 122 publications

A Tale of Two Cancers: A Current Concise Overview of Breast and Prostate Cancer

A Tale of Two Cancers: A Current Concise Overview of Breast and Prostate Cancer

Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy

A Multimodal Therapeutic Nanoplatform Overcoming Tumor Hypoxia Heterogeneity for Improved Tumor Chemoradiotherapy

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