Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Фев. 17, 2023

Abstract Having a hypoxic microenvironment is common and salient feature of most solid tumors. Hypoxia has profound effect on the biological behavior malignant phenotype cancer cells, mediates effects chemotherapy, radiotherapy, immunotherapy through complex mechanisms, closely associated with poor prognosis in various patients. Accumulating studies have demonstrated that normalization tumor vasculature, nanoparticle carriers biocarriers can effectively increase oxygen concentration microenvironment, improve drug delivery efficacy radiotherapy. They also infiltration innate adaptive anti-tumor immune cells to enhance immunotherapy. Furthermore, drugs targeting key genes hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, hypoxia-inducible factors downstream targets, be used for visualization quantitative analysis antitumor activity. However, relationship between an area research requires further exploration. Here, we investigated potential development cancer, changes signaling pathways occur adapt environments, mechanisms hypoxia-induced tolerance, chemotherapeutic enhanced radiation as well insights applications therapy.

Язык: Английский

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Engineering nanomedicine for glutathione depletion-augmented cancer therapy

Chemical Society Reviews, Год журнала: 2021, Номер 50(10), С. 6013 - 6041

Опубликована: Янв. 1, 2021

In this review, we systematically survey the most recent progress in engineering nanomedicine for intracellular glutathione consumption-augmented cancer therapy.

Язык: Английский

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Overcoming barriers in photodynamic therapy harnessing nano-formulation strategies

Chemical Society Reviews, Год журнала: 2021, Номер 50(16), С. 9152 - 9201

Опубликована: Янв. 1, 2021

Photodynamic therapy (PDT) has been extensively investigated for decades tumor treatment because of its non-invasiveness, spatiotemporal selectivity, lower side-effects, and immune activation ability.

Язык: Английский

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Recent Advances in Hyperthermia Therapy‐Based Synergistic Immunotherapy

Advanced Materials, Год журнала: 2020, Номер 33(4)

Опубликована: Дек. 2, 2020

Abstract The past decades have witnessed hyperthermia therapy (HTT) as an emerging strategy against malignant tumors. Nanomaterial‐based photothermal (PTT) and magnetic (MHT), highly effective noninvasive treatment models, offer advantages over other strategies in the of different types However, both PTT MHT cannot completely cure cancer due to recurrence distal metastasis. In recent years, immunotherapy has attracted widespread attention owing its capability activate body's own natural defense identify, attack, eradicate cells. Significant efforts been devoted studying activated immune responses caused by hyperthermia‐ablated this article, synergistic mechanism HTT immunotherapy, including immunogenic cell death reversal immunosuppressive tumor microenvironment is discussed. reports combination or HTT‐based multimodal with immunoadjuvant exploitation, checkpoint blockade therapy, adoptive cellular are summarized. As highlighted, these could achieve synergistically enhanced therapeutic outcomes primary tumors metastatic lesions, prevent recurrence, prolong survival period. Finally, current challenges prospective developments HTT‐synergized also reviewed.

Язык: Английский

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Semiconducting polymer nano-PROTACs for activatable photo-immunometabolic cancer therapy

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Май 18, 2021

Abstract Immunometabolic intervention has been applied to treat cancer via inhibition of certain enzymes associated with intratumoral metabolism. However, small-molecule inhibitors and genetic modification often suffer from insufficiency off-target side effects. Proteolysis targeting chimeras (PROTACs) provide an alternative way modulate protein homeostasis for therapy; however, the always-on bioactivity existing PROTACs potentially leads uncontrollable degradation at non-target sites, limiting their in vivo therapeutic efficacy. We herein report a semiconducting polymer nano-PROTAC (SPN pro ) phototherapeutic activatable abilities photo-immunometabolic therapy. SPN can remotely generate singlet oxygen ( 1 O 2 under NIR photoirradiation eradicate tumor cells induce immunogenic cell death (ICD) enhance immunogenicity. Moreover, PROTAC function is specifically activated by biomarker (cathepsin B) trigger targeted proteolysis immunosuppressive indoleamine 2,3-dioxygenase (IDO) living mice. The persistent IDO blocks tryptophan (Trp)-catabolism program promotes activation effector T cells. Such SPNpro-mediated in-situ immunometabolic synergizes phototherapy boost antitumor T-cell immunity, effectively inhibiting growth metastasis. Thus, this study provides platform advance

Язык: Английский

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Second Near‐Infrared Photothermal Semiconducting Polymer Nanoadjuvant for Enhanced Cancer Immunotherapy

Advanced Materials, Год журнала: 2020, Номер 33(4)

Опубликована: Дек. 16, 2020

Abstract Immunotherapy has offered new treatment options for cancer; however, the therapeutic benefits are often modest and desired to be improved. A semiconducting polymer nanoadjuvant (SPN II R) with a photothermally triggered cargo release second near‐infrared (NIR‐II) photothermal immunotherapy is reported here. SPN R consists of nanoparticle core as an NIR‐II converter, which doped toll‐like receptor (TLR) agonist adjuvant coated thermally responsive lipid shell. Upon photoirradiation, effectively generates heat not only ablate tumors induce immunogenic cell death (ICD), but also melt layers on‐demand TLR agonist. The combination ICD activation TLR7/TLR8 enhances maturation dendritic cells, amplifies anti‐tumor immune responses. Thus, single R‐mediated inhibits growth both primary distant eliminates lung metastasis in murine mouse model. This study thus provides remote‐controlled smart delivery system synergize photomedicine enhanced cancer treatment.

Язык: Английский

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Near-infrared photoactivated nanomedicines for photothermal synergistic cancer therapy

Nano Today, Год журнала: 2021, Номер 37, С. 101073 - 101073

Опубликована: Янв. 10, 2021

Язык: Английский

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<p>Pathological Mechanism of Photodynamic Therapy and Photothermal Therapy Based on Nanoparticles</p>

International Journal of Nanomedicine, Год журнала: 2020, Номер Volume 15, С. 6827 - 6838

Опубликована: Сен. 1, 2020

Abstract: The ultimate goal of phototherapy based on nanoparticles, such as photothermal therapy (PTT) which generates heat and photodynamic (PDT) not only reactive oxygen species (ROS) but also induces a variety anti-tumor immunity, is to kill tumors. In addition, due strong efficacy in clinical treatment with minimal invasion negligible side effects, it has received extensive attention research recent years. this paper, the generations nanomaterials PTT PDT are described separately. application, according different combination pathway can be used treat diseases tumors, melanoma, rheumatoid so on. mechanism pathological detail terms inducing apoptosis cancer cells by ROS produced PDT, immunogenic cell death provoke maturation dendritic cells, turn activate production CD4+ T CD8+T memory well inhibiting shock protein (HSPs), STAT3 signal Keywords: mechanism, therapy, PTT,

Язык: Английский

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Activatable Polymer Nanoenzymes for Photodynamic Immunometabolic Cancer Therapy

Advanced Materials, Год журнала: 2020, Номер 33(4)

Опубликована: Дек. 11, 2020

Abstract Tumor immunometabolism contributes substantially to tumor proliferation and immune cell activity, thus plays a crucial role in the efficacy of cancer immunotherapy. Modulation boost immunotherapy is mostly based on small‐molecule inhibitors, which often encounter issues off‐target adverse effects, drug resistance, unsustainable response. In contrast, enzymatic therapeutics can potentially bypass these limitations but has been less exploited. Herein, an organic polymer nanoenzyme (SPNK) with near‐infrared (NIR) photoactivatable immunotherapeutic effects reported for photodynamic immunometabolic therapy. SPNK composed semiconducting core conjugated kynureninase (KYNase) via PEGylated singlet oxygen ( 1 O 2 ) cleavable linker. Upon NIR photoirradiation, generates not only exert effect induce immunogenic death cancer, also unleash KYNase trigger its activity degrade immunosuppressive kynurenine (Kyn). Such combinational mediated by promotes infiltration effector T cells, enhances systemic antitumor immunity, ultimately permits inhibition both primary distant tumors living mice. Therefore, this study provides promising approach toward remotely controlled immunomodulation improved anticancer

Язык: Английский

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Transformable Nanosensitizer with Tumor Microenvironment‐Activated Sonodynamic Process and Calcium Release for Enhanced Cancer Immunotherapy

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(25), С. 14051 - 14059

Опубликована: Апрель 2, 2021

Abstract Despite the promise of sonodynamic processes in cancer therapy, existing sonosensitizers often fail to regulate generation reactive oxygen species (ROS) against tumors, potentially leading off‐target toxicity normal tissues. We report a transformable core‐shell nanosonosensitizer (TiO 2 @CaP) that reinvigorates ROS and dissolves its CaP shell release Ca 2+ an acidic tumor microenvironment (TME) under ultrasound activation. Thus, TiO @CaP acts as smart specifically induces mitochondrial dysfunction via overloading intracellular ions synergize with process TME. substantially enhances immunogenic cell death, resulting enhanced T‐cell recruitment infiltration into cold (4T1). In conjunction checkpoint blockade therapy (anti‐PD 1), @CaP‐mediated elicits systemic antitumor immunity, regression non‐treated distant tumors inhibition lung metastasis. This work paves way development “smart” TME‐activatable temporospatial control over responses.

Язык: Английский

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