Turning cold tumors into hot tumors by improving T-cell infiltration

Theranostics, Год журнала: 2021, Номер 11(11), С. 5365 - 5386

Опубликована: Янв. 1, 2021

Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has greatly improved the clinical efficacy of malignant tumor therapy. ICI-mediated antitumor responses depend on infiltration T cells capable recognizing and killing cells. ICIs are not effective in "cold tumors", which characterized lack T-cell infiltration. To realize full potential immunotherapy solve this obstacle, it is essential to understand drivers into tumors. We present a critical review our understanding mechanisms underlying including impaired priming deficient homing beds. "Hot tumors" with significant associated better ICI efficacy. In review, we summarize multiple strategies that promote transformation "hot discuss these lead increased Finally, application nanomaterials provide an outlook future emerging field. The combination nanomedicines enhances cross-presentation antigens promotes A deeper opens new possibilities for development cell-based therapies improve effectiveness.

Язык: Английский

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Stimuli-responsive nanocarriers for drug delivery, tumor imaging, therapy and theranostics

Theranostics, Год журнала: 2020, Номер 10(10), С. 4557 - 4588

Опубликована: Янв. 1, 2020

In recent years, much progress has been motivated in stimuli-responsive nanocarriers, which could response to the intrinsic physicochemical and pathological factors diseased regions increase specificity of drug delivery. Currently, numerous nanocarriers have engineered with changes responding external stimuli, such as ultrasound, thermal, light magnetic field, well internal including pH, redox potential, hypoxia enzyme, etc. Nanocarriers respond stimuli tumor microenvironments or inside cancer cells for on-demanded delivery accumulation, controlled release, activation bioactive compounds, probes targeting ligands, size, charge conformation conversion, etc., leading sensing signaling, overcoming multidrug resistance, accurate diagnosis precision therapy. This review summarized general strategies developing advances, presented their applications delivery, imaging, therapy theranostics, illustrated clinical translation made prospects.

Язык: Английский

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Recent Advances in Nanomaterial‐Assisted Combinational Sonodynamic Cancer Therapy

Advanced Materials, Год журнала: 2020, Номер 32(47)

Опубликована: Окт. 16, 2020

Ultrasound (US)-triggered sonodynamic therapy (SDT), as a promising noninvasive therapeutic modality, has received ever-increasing attention in recent years. Its specialized chemical agents, named sonosensitizers, are activated by low-intensity US to produce lethal reactive oxygen species (ROS) for oncotherapy. Compared with phototherapeutic strategies, SDT provides many noteworthy opportunities and benefits, such deeper penetration depth, absence of phototoxicity, fewer side effects. Nevertheless, previous studies have also demonstrated its intrinsic limitations. Thanks the facile engineering nature nanotechnology, numerous novel nanoplatforms being applied this emerging field tackle these barriers achieve continuous innovations. In particular, combination other treatment strategies superior efficacy improving anticancer activity relative that monotherapies alone. Therefore, it is necessary summarize nanomaterial-assisted combinational cancer applications. Herein, design principles achieving synergistic effects based on nanomaterial methods highlighted. The ultimate goals stimulate better-quality combined schemes provide innovative ideas perspectives promoting future transformation clinical application.

Язык: Английский

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Immunogenic Cell Death Activates the Tumor Immune Microenvironment to Boost the Immunotherapy Efficiency

Advanced Science, Год журнала: 2022, Номер 9(22)

Опубликована: Июнь 2, 2022

Abstract Tumor immunotherapy is only effective in a fraction of patients due to low response rate and severe side effects, these challenges clinics can be addressed through induction immunogenic cell death (ICD). ICD elicited from many antitumor therapies release danger associated molecular patterns (DAMPs) tumor‐associated antigens facilitate maturation dendritic cells (DCs) infiltration cytotoxic T lymphocytes (CTLs). The process reverse the tumor immunosuppressive microenvironment improve sensitivity immunotherapy. Nanostructure‐based drug delivery systems (NDDSs) are explored induce by incorporating therapeutic molecules for chemotherapy, photosensitizers (PSs) photodynamic therapy (PDT), photothermal conversion agents (PTT), radiosensitizers radiotherapy (RT). These NDDSs loaded at right dose place time, resulting greater effectiveness lower toxicity. Immunotherapeutic also combined with achieve synergic effect multi‐modality approach. In this review, harnessed load multiple PDT, PTT, RT combination promote reduce effects cancer treatment.

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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Difunctionalization of Alkenes Involving Metal Migration

Angewandte Chemie International Edition, Год журнала: 2019, Номер 59(21), С. 7990 - 8003

Опубликована: Дек. 4, 2019

The direct difunctionalization of alkenes, a cheap and abundant feedstock, represents one the most attractive strategies for increasing molecular complexity in synthetic organic chemistry. In contrast with 1,2-difunctionalization recent advances showcase alkene 1,n-difunctionalizations (n≠2) involving metal migration is an emerging rapidly growing area research. This promising strategy not only opens novel avenue future development transformations, but also significantly expands upon bond disconnections available modern synthesis. Minireview summarizes progress migratory emphasis on driving force migration.

Язык: Английский

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Tumor‐Microenvironment‐Responsive Nanomedicine for Enhanced Cancer Immunotherapy

Advanced Science, Год журнала: 2021, Номер 9(1)

Опубликована: Ноя. 19, 2021

Abstract The past decades have witnessed great progress in cancer immunotherapy, which has profoundly revolutionized oncology, whereas low patient response rates and potential immune‐related adverse events remain major clinical challenges. With the advantages of controlled delivery modular flexibility, nanomedicine offered opportunities to strengthen antitumor immune responses sensitize tumor immunotherapy. Furthermore, tumor‐microenvironment (TME)‐responsive been demonstrated achieve specific localized amplification tissue a safe effective manner, increasing immunotherapy reducing side effects simultaneously. Here, recent TME‐responsive for is summarized, responds signals TME, such as weak acidity, reductive environment, high‐level reactive oxygen species, hypoxia, overexpressed enzymes, adenosine triphosphate. Moreover, combine nanomedicine‐based therapy immunotherapeutic strategies overcome each step cancer‐immunity cycle enhance discussed. Finally, existing challenges further perspectives this rising field with hope improved development applications are

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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Artificial Enzyme Catalyzed Cascade Reactions: Antitumor Immunotherapy Reinforced by NIR‐II Light

Angewandte Chemie International Edition, Год журнала: 2019, Номер 58(48), С. 17425 - 17432

Опубликована: Сен. 25, 2019

Abstract Current cancer therapy is seriously challenged by tumor metastasis and recurrence. One promising solution to these problems build antitumor immunity. However, immunotherapeutic efficacy highly impeded the immunosuppressive state of tumors. Here a new strategy presented, catalytic immunotherapy based on artificial enzymes. Cu 2− x Te nanoparticles exhibit tunable enzyme‐mimicking activity (including glutathione oxidase peroxidase) under near‐infrared‐II (NIR‐II) light. The cascade reactions catalyzed enzyme gradually elevates intratumor oxidative stress induce immunogenic cell death. Meanwhile, continuously generated reverses microenvironment, boosts immune responses eradicate both primary distant metastatic Moreover, immunological memory effect successfully acquired after treatment with suppress relapse.

Язык: Английский

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Fighting Immune Cold and Reprogramming Immunosuppressive Tumor Microenvironment with Red Blood Cell Membrane-Camouflaged Nanobullets

ACS Nano, Год журнала: 2020, Номер 14(12), С. 17442 - 17457

Опубликована: Ноя. 9, 2020

Nanomedicine, acting as the magic bullet, is capable of combining immunotherapy with other treatments to reverse a cold tumor (immune depletion) into hot tumor. However, how comprehensively inhibit immunosuppressive microenvironment (TME) remains major challenge for achieve maximum benefits. Thus, strategy that can simultaneously increase recruitment infiltrating lymphocytes (TILs) and reprogram TME still urgently needed. Herein, thermal-sensitive nitric oxide (NO) donor S-nitrosothiols (SNO)-pendant copolymer (poly(acrylamide-co-acrylonitrile-co-vinylimidazole)-SNO copolymer, PAAV-SNO) upper critical solution temperature (UCST) was synthesized employed fabricate an erythrocyte membrane-camouflaged nanobullet codelivery NIR II photothermal agent IR1061 indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor 1-methyl-tryptophan (1-MT). This multifunctional possessed long circulation in vivo, enhanced accumulation at site, therapeutics-controlled release by laser, thereby it could avoid unspecific drug leakage while enhancing biosecurity. More importantly, immunogenic cell death (ICD) induced local hyperthermia from therapy (PTT) be conducive increased CD8+ cytotoxic T (CTLs) site. Furthermore, through interfering IDO-1 activity 1-MT normalizing vessels situ generated NO, reprogrammed toward immunostimulatory phenotype, achieving excellent therapeutic efficacy against both primary breast cancer metastases. Collectively, this described study developed effective promising suppressive treat "immune cold" tumors.

Язык: Английский

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