Peptide‐Appended Nanosonosensitizers Targeting Tumor Glycolysis for Synergistic Sonodynamic–Immunometabolic Therapy of Spinal‐Metastasized Tumors DOI
Ziyang Chen, Liang Chen, Yiqun Ma

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(42)

Published: July 18, 2023

Despite recent advancements in cancer immunotherapy, challenges have yet to be surmounted achieve two major goals of magnifying antitumor immunity and remodeling the immunosuppressive tumor microenvironment. Here, a nanosystem (ODM-R) that integrates oxygen-deficient molybdenum oxide (ODM) nanosonosensitizers R7 peptides with metabolism regulation effects is designed fabricated for synergistic sonodynamic-immunometabolic therapy spinal-metastasized tumors. The ODM generates reactive oxygen species upon ultrasound irradiation implement sonodynamic (SDT), inducing cell apoptosis immunogenic death. attached on markedly inhibits uptake glucose excretion lactic acid cells by perturbing glycolysis process. combination SDT obstruction ODM-R guarantees satisfactory efficacy synergizing PD-L1 antibody eradicate tumors, achieving concurrent sonodynamic-triggered immune activation microenvironment remodeling. This work provides proof-of-concept boosting immunotherapy metabolic regulation.

Language: Английский

Targeting p53 pathways: mechanisms, structures and advances in therapy DOI Creative Commons

Haolan Wang,

Ming Guo,

Hudie Wei

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 1, 2023

The TP53 tumor suppressor is the most frequently altered gene in human cancers, and has been a major focus of oncology research. p53 protein transcription factor that can activate expression multiple target genes plays critical roles regulating cell cycle, apoptosis, genomic stability, widely regarded as "guardian genome". Accumulating evidence shown also regulates metabolism, ferroptosis, microenvironment, autophagy so on, all which contribute to suppression. Mutations not only impair its function, but confer oncogenic properties mutants. Since mutated inactivated malignant tumors, it very attractive for developing new anti-cancer drugs. However, until recently, was considered an "undruggable" little progress made with p53-targeted therapies. Here, we provide systematic review diverse molecular mechanisms signaling pathway how mutations impact progression. We discuss key structural features inactivation by mutations. In addition, efforts have therapies, challenges encountered clinical development.

Language: Английский

Citations

420
Harnessing Nanomaterials for Cancer Sonodynamic Immunotherapy DOI
Shuang Liang, Jianjun Yao, Dan Liu

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(33)

Published: March 7, 2023

Abstract Immunotherapy has made remarkable strides in cancer therapy over the past decade. However, such emerging still suffers from low response rates and immune‐related adverse events. Various strategies have been developed to overcome these serious challenges. Therein, sonodynamic (SDT), as a non‐invasive treatment, received ever‐increasing attention especially treatment of deep‐seated tumors. Significantly, SDT can effectively induce immunogenic cell death trigger systemic anti‐tumor immune response, termed immunotherapy. The rapid development nanotechnology revolutionized effects with robust induction. As result, more innovative nanosonosensitizers synergistic modalities are established superior efficacy safe profile. In this review, recent advances immunotherapy summarized particular emphasis on how be explored harness for amplifying response. Moreover, current challenges field prospects its clinical translation also presented. It is anticipated that review provide rational guidance facilitate nanomaterials‐assisted immunotherapy, helping pave way next‐generation eventually achieve durable patients.

Language: Английский

Citations

142
Organic Sonodynamic Materials for Combination Cancer Immunotherapy DOI
Chi Zhang, Kanyi Pu

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(51)

Published: June 1, 2023

Sonodynamic therapy (SDT) is a promising non-invasive therapeutic modality to treat deep-seated tumors owing the good tissue penetration ability and spatiotemporal controllability of ultrasound (US); however, low sonodynamic activity potential side effects greatly limit its clinical translation. Cancer immunotherapy that leverages immune system fight against cancer has great synergize with SDT for treatment high efficiency safety. In this review, convergence exert their merits break through limitations combination sono-immunotherapy are discussed. The focus on development construction organic materials immunotherapeutic efficiency. These not only induce immunogenic cell death improve tumor immunogenicity via but also activate antitumor immunity immuno-oncology drug-mediated pathway modulation. various drugs sonosensitizers categorized discussed along prospects challenges

Language: Английский

Citations

83
State of the art advancements in sonodynamic therapy (SDT): Metal-Organic frameworks for SDT DOI

Zuoxiu Xiao,

Qiaohui Chen, Yuqi Yang

et al.

Chemical Engineering Journal, Journal Year: 2022, Volume and Issue: 449, P. 137889 - 137889

Published: July 4, 2022

Language: Английский

Citations

76
Checkpoint Nano‐PROTACs for Activatable Cancer Photo‐Immunotherapy DOI
Chi Zhang,

Mengke Xu,

Shasha He

et al.

Advanced Materials, Journal Year: 2022, Volume and Issue: 35(6)

Published: Nov. 25, 2022

Abstract Checkpoint immunotherapy holds great potential to treat malignancies via blocking the immunosuppressive signaling pathways, which however suffers from inefficiency and off‐target adverse effects. Herein, checkpoint nano‐proteolysis targeting chimeras (nano‐PROTACs) in combination with photodynamic tumor regression protein degradation block pathways for activatable cancer photo‐immunotherapy are reported. These nano‐PROTACs composed of a photosensitizer (protoporphyrin IX, PpIX) an Src homology 2 domain‐containing phosphatase (SHP2)‐targeting PROTAC peptide (aPRO) caspase 3‐cleavable segment. aPRO is activated by increased expression 3 cells after phototherapeutic treatment induces targeted SHP2 ubiquitin‐proteasome system. The persistent depletion blocks (CD47/SIRPα PD‐1/PD‐L1), thus reinvigorating antitumor macrophages T cells. Such strategy synergizes immunogenic phototherapy boost immune response. Thus, this study represents generalized platform modulate immune‐related improved anticancer therapy.

Language: Английский

Citations

76
Oxygen‐Deficient Molybdenum Oxide Nanosensitizers for Ultrasound‐Enhanced Cancer Metalloimmunotherapy DOI

Yuanjie Wang,

Fei Gong, Zhihui Han

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(9)

Published: Jan. 2, 2023

Oxygen-deficient molybdenum oxide (MoOX ) nanomaterials are prepared as novel nanosensitizers and TME-stimulants for ultrasound (US)-enhanced cancer metalloimmunotherapy. After PEGylation, MoOX -PEG exhibits efficient capability US-triggered reactive oxygen species (ROS) generation glutathione (GSH) depletion. Under US irradiation, generates a massive amount of ROS to induce cell damage immunogenic death (ICD), which can effectively suppress tumor growth. More importantly, itself further stimulates the maturation dendritic cells (DCs) triggeres activation cGAS-STING pathway enhance immunological effect. Due robust ICD induced by SDT DC stimulated -PEG, combination treatment -triggered aCTLA-4 amplifies antitumor therapy, inhibits metastases, elicits immune responses defeat abscopal tumors.

Language: Английский

Citations

72
Genetically Engineering Cell Membrane‐Coated BTO Nanoparticles for MMP2‐Activated Piezocatalysis‐Immunotherapy DOI

Qingshuang Tang,

Suhui Sun,

Ping Wang

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(18)

Published: Feb. 21, 2023

Tumor immunotherapy based on immune checkpoint blockade (ICB) still suffers from low host response rate and non-specific distribution of inhibitors, greatly compromising the therapeutic efficiency. Herein, cellular membrane stably expressing matrix metallopeptidase 2 (MMP2)-activated PD-L1 blockades is engineered to coat ultrasmall barium titanate (BTO) nanoparticle for overcoming immunosuppressive microenvironment tumors. The resulting M@BTO NPs can significantly promote BTO's tumor accumulation, while masking domains antibodies are cleaved when exposure MMP2 highly expressed in tumor. With ultrasound (US) irradiation, simultaneously generate reactive oxygen species (ROS) O2 BTO mediated piezocatalysis water splitting, promoting intratumoral infiltration cytotoxic T lymphocytes (CTLs) improving therapy tumor, effective growth inhibition lung metastasis suppression a melanoma mouse model. This nanoplatform combines MMP2-activated genetic editing cell with US responsive both stimulation specific inhibition, providing safe robust strategy enhancing against

Language: Английский

Citations

69
Dual‐Cascade Activatable Nanopotentiators Reshaping Adenosine Metabolism for Sono‐Chemodynamic‐Immunotherapy of Deep Tumors DOI Creative Commons
Meixiao Zhan,

Fengshuo Wang,

Yao Liu

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(10)

Published: Feb. 2, 2023

Immunotherapy is an attractive treatment strategy for cancer, while its efficiency and safety need to be improved. A dual-cascade activatable nanopotentiator sonodynamic therapy (SDT) chemodynamic (CDT)-cooperated immunotherapy of deep tumors via reshaping adenosine metabolism herein reported. This (NPMCA) constructed through crosslinking deaminase (ADA) with chlorin e6 (Ce6)-conjugated manganese dioxide (MnO2) nanoparticles a reactive oxygen species (ROS)-cleavable linker. In the tumor microenvironment ultrasound (US) irradiation, NPMCA mediates CDT SDT concurrently in covered 2-cm tissues produce abundant ROS, which results scissoring ROS-cleavable linkers activate ADA within NCMCA block metabolism. Moreover, immunogenic cell death (ICD) dying cells upregulation stimulator interferon genes (STING) triggered by generated ROS Mn2+ from NPMCA, respectively, leading activation antitumor immune response. The potency response further reinforced reducing accumulation activated ADA. As result, enables SDT-cooperated immunotherapy, showing obviously improved therapeutic efficacy inhibit growths bilateral tumors, primary are tissues.

Language: Английский

Citations

66
An Activatable Phototheranostic Probe for Anti‐hypoxic Type I Photodynamic‐ and Immuno‐Therapy of Cancer DOI Open Access
Min Zhao, Yuyang Zhang,

Jia Miao

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(4)

Published: Aug. 29, 2023

Photodynamic therapy (PDT), which utilizes type I photoreactions, has great potential as an effective cancer treatment because of its hypoxia-tolerant superiority over the commonly used II pathway. A few photosensitizers are exploited; however, they majorly induce cytotoxicity and possess poor tumor specificity low-efficient theranostics. To resolve this issue, herein aminopeptidase N (APN)-activated phototheranostic probe (CyA) is reported for anti-hypoxic PDT in conjunction with immunotherapy treatment. CyA can specifically activate near-infrared fluorescence, photoacoustic signals, phototoxicity following APN-induced substrate cleavage subsequent generation active molecules (such CyBr). endows specific imaging capabilities toward cells overexpressing APN under both normoxia hypoxia. In addition, locally activatable induces systemic antitumor immune responses. More importantly, integration localized activated evokes enhanced therapeutic effects improved inhibition efficiency live mice compared individual treatments. This study aims to present combination therapy.

Language: Английский

Citations

65
Augmenting Immunogenic Cell Death and Alleviating Myeloid‐Derived Suppressor Cells by Sono‐Activatable Semiconducting Polymer Nanopartners for Immunotherapy DOI

Mengbin Ding,

Yijing Zhang,

Ningyue Yu

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(33)

Published: May 11, 2023

Inducing immunogenic cell death (ICD) by sonodynamic therapy (SDT) is promising for cancer immunotherapy, which however inefficient due to oxygen depletion that compromises SDT effect and mediates recruitment of immunosuppressive myeloid-derived suppressor cells (MDSCs). The fabrication sono-activatable semiconducting polymer nanopartners (SPNTi ) simultaneously augment ICD alleviate MDSCs immunotherapy reported. A polymer, hydrophobic hypoxia-responsive tirapazamine (TPZ)-conjugate, MDSC-targeting drug (ibrutinib) are encapsulated inside such SPNTi with surface shell a singlet (1 O2 )-cleavable amphiphilic polymer. TPZ ibrutinib serve as partners enlarge immunotherapeutic effect. Upon sono-activation, generate 1 break -cleavable polymers in situ liberations TPZ-conjugate tumor sites, consumed create severe hypoxic microenvironment, which, activated augmenting action, while alleviates promoting antitumor immunological In bilateral mouse model, -mediated results growth restraints primary distant tumors noteworthy precaution metastases. This study thus provides strategy high precision safety via overcoming post-treatment hypoxia targeting MDSCs.

Language: Английский

Citations

59