A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 25, 2023

Precise and efficient image-guided immunotherapy holds great promise for cancer treatment. Here, we report a self-accelerated nanoplatform combining an aggregation-induced emission luminogen (AIEgen) hypoxia-responsive prodrug multifunctional combination immunotherapy. The near-infrared AIEgen with methoxy substitution simultaneously possesses boosted fluorescence photoacoustic (PA) brightness the strong light absorption ability, as well amplified type I II photodynamic therapy (PDT) properties via enhanced intersystem crossing process. By formulating high-performance paclitaxel (PTX) into nanoparticles, further camouflaging macrophage cell membrane, tumor-targeting theranostic agent is built. integration of PA imaging helps to delineate tumor site sensitively, providing accurate guidance light-induced PDT effect could consume local oxygen lead severer hypoxia, accelerating release PTX drug. As result, chemotherapy induces immunogenic death, which not only elicit antitumor immunity suppress primary tumor, but also inhibit growth distant in 4T1 tumor-bearing female mice. strategy develop agents rational molecular design boosting

Language: Английский

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Correlation between PD-1/PD-L1 expression and polarization in tumor-associated macrophages: A key player in tumor immunotherapy

Cytokine & Growth Factor Reviews, Journal Year: 2022, Volume and Issue: 67, P. 49 - 57

Published: July 18, 2022

Tumor immunotherapy, such as PD-1/PD-L1 blockade, has shown promising clinical efficacy in patients with various types of tumors. However, the response to blockade a majority malignancies is limited, indicating an urgent need for deeper understanding mechanisms axis-mediated tumor tolerance. As most abundant immune cells stroma, macrophages display multiple phenotypes and functions stimuli microenvironment. been demonstrated be highly expressed tumor-associated (TAMs), TAM polarization important during progression. In this review, we outline relationship between expression polarizations, summarize involvement M2 TAMs PD-1/PD-L1-mediated T-cell exhaustion, discuss improved approaches overcoming resistance by inducing M2/M1 switching TAMs.

Language: Английский

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Extracellular‐Vesicle‐Based Drug Delivery Systems for Enhanced Antitumor Therapies through Modulating the Cancer‐Immunity Cycle

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(52)

Published: June 21, 2022

Although immunotherapy harnessing activity of the immune system against tumors has made great progress, treatment efficacy remains limited in most cancers. Current anticancer is primarily based on T-cell-mediated cellular immunity, which highly relies efficiency triggering cancer-immunity cycle, namely, tumor antigen release, presentation by presenting cells, T cell activation, recruitment and infiltration cells into tumors, recognition killing cells. Unfortunately, these immunotherapies are restricted inefficient drug delivery acting only a single step cycle. Due to high biocompatibility, low immunogenicity, intrinsic targeting, easy chemical genetic manipulation, extracellular vesicle (EV)-based systems widely used amplify responses serving as an integrated platform for multiple drugs or therapeutic strategies synergistically activate several steps This review summarizes various mechanisms related affecting cycle disorders. Meanwhile, preparation application EV-based modulating introduced, especially improvement tumors. Finally, opportunities challenges translational clinical applications briefly discussed.

Language: Английский

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Extracellular Vesicles‐Derived Hybrid Nanoplatforms for Amplified CD47 Blockade‐Based Cancer Immunotherapy

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

Published: June 29, 2023

Immunomodulation of tumor-associated macrophages (TAMs) into tumor-inhibiting M1-like phenotype is a promising but challenging strategy. Cleverly, tumor cells overexpress CD47, "don't eat me" signal that ligates with the regulatory protein alpha (SIRPα) on to escape phagocytosis. Thus, effective re-education TAMs "eat type and blocking CD47-SIRPα signaling play pivotal roles in immunotherapy. Herein, it reported hybrid nanovesicles (hEL-RS17) derived from extracellular vesicles M1 decorated RS17 peptide, an antitumor peptide specifically binds CD47 blocks signaling, can actively target remodel TAM phenotypes. Consequently, more infiltrate tissue phagocytize due blockade. By further co-encapsulating chemotherapeutic agent shikonin, photosensitizer IR820, immunomodulator polymetformin hEL-RS17, enhanced effect obtained combinational treatment modality close synergy among each component. Upon laser irradiation, designed SPI@hEL-RS17 nanoparticles exert potent efficacy against both 4T1 breast B16F10 melanoma models, which not only suppresses primary growth also inhibits lung metastasis prevents recurrence, exhibiting great potential boosting blockade-based

Language: Английский

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Boosting Checkpoint Immunotherapy with Biomaterials

ACS Nano, Journal Year: 2023, Volume and Issue: 17(4), P. 3225 - 3258

Published: Feb. 6, 2023

The immune checkpoint blockade (ICB) therapy has revolutionized the field of cancer treatment, while low response rates and systemic toxicity limit its clinical outcomes. With rapid advances in nanotechnology materials science, various types biomaterials have been developed to maximize therapeutic efficacy minimizing side effects by increasing tumor antigenicity, reversing immunosuppressive microenvironment, amplifying antitumor response, reducing extratumoral distribution inhibitors as well enhancing their retention within target sites. In this review, we reviewed current design strategies for different augment ICB effectively then discussed present representative biomaterial-assisted modulation targeted delivery boost therapy. Current challenges future development prospects expanding with were also summarized. We anticipate review will be helpful developing emerging promoting application

Language: Английский

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Cell microparticles loaded with tumor antigen and resiquimod reprogram tumor-associated macrophages and promote stem-like CD8+ T cells to boost anti-PD-1 therapy

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 13, 2023

Abstract The durable response rate to immune checkpoint blockade such as anti-programmed cell death-1 (PD-1) antibody remains relatively low in hepatocellular carcinoma (HCC), mainly depending on an immunosuppressive microenvironment with limited number of CD8 + T cells, especially stem-like tumor tissues. Here we develop engineered microparticles (MPs) derived from alpha-fetoprotein (AFP)-overexpressing macrophages load resiquimod (R848@M2pep-MPs AFP ) for enhanced anti-PD-1 therapy HCC. R848@M2pep-MPs target and reprogram M2-like tumor-associated (TAMs) into M1-like phenotype. Meanwhile, -reprogrammed TAMs act antigen-presenting not only presenting antigen activate cell-mediated antitumor immunity, but also providing intra-tumoral niche maintain differentiate cells. Combination immunotherapy generates strong memory induces abundant proliferation differentiation terminally exhausted cells long-term surveillance orthotopic autochthonous HCC preclinical models male mice. We show that the R848-loaded MPs overexpressing a model ovalbumin (OVA) can improve melanoma B16-OVA tumor-bearing Our work presents facile generic strategy personalized cancer boost therapy.

Language: Английский

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Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

Advanced Science, Journal Year: 2023, Volume and Issue: 10(22)

Published: May 28, 2023

Abstract Lung cancer is a commonly diagnosed disease worldwide, with non‐small cell lung cancers (NSCLCs) accounting for ≈ 85% of cases. Cigarette smoke an environmental exposure promoting progression NSCLC, but its role poorly understood. This study reports that smoking‐induced accumulation M2‐type tumor‐associated macrophages (M2‐TAMs) surrounding NSCLC tissues promotes malignancy. Specifically, extracellular vesicles (EVs) from cigarette extract (CSE)‐induced M2 promoted malignancy cells in vitro and vivo. circEML4 EVs CSE‐induced transported to cells, where it reduced the distribution ALKBH5 nucleus by interacting Human AlkB homolog H5 (ALKBH5), resulting elevated N6‐methyladenosine (m6A) modifications. m6A‐seq RNA‐seq revealed suppressor cytokine signaling 2 (SOCS2)‐mediated activation Janus kinase‐signal transducer activator transcription (JAK‐STAT) pathway regulating m6A modification SOCS2 via ALKBH5. Down‐regulation reversed EVs‐enhanced tumorigenicity metastasis cells. Furthermore, this found smoking patients showed increase circEML4‐positive M2‐TAMs. These results indicate M2‐TAMs promote through ALKBH5‐regulated SOCS2. also reveals TAMs acts as diagnostic biomarker especially history.

Language: Английский

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A Vanadium-Based Nanoplatform Synergizing Ferroptotic-like Therapy with Glucose Metabolism Intervention for Enhanced Cancer Cell Death and Antitumor Immunity

ACS Nano, Journal Year: 2023, Volume and Issue: 17(12), P. 11537 - 11556

Published: June 5, 2023

Ferroptosis activation has been considered a mighty weapon for cancer treatment, and growing attention is being paid to reinforcing tumor cells' sensitivity ferroptosis. However, the existence of certain ferroptosis resistance mechanisms, especially abnormal metabolism cells, long underestimated. We propose an enhanced ferroptosis-activating pattern via regulating glycometabolism construct nanoplatform named PMVL, which composed lonidamine (LND)-loaded tannic acid coordinated vanadium oxides with camouflage PD-L1 inhibiting peptide-modified cell membrane. This work reveals that mixed valence (VIV VV) in PMVL triggers due self-cyclic alteration V, process generates •OH lipid peroxide accumulation → depletes glutathione (GSH) peroxidase (GPX4) deactivation (VV VIV). Notably, LND strengthens by dual suppression glycolysis (decreasing ATP supply) pentose phosphate pathway NADPH production), causing anabatic GSH consumption. Besides, inhibited less intracellular lactic alleviates acidity microenvironment, preventing immunosuppressive M2 macrophage polarization. In vitro vivo data demonstrate glycometabolism-intervention-enhanced boosted immunity activation, potentially providing opportunities possibilities synergetic therapy.

Language: Английский

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Enhancing drug penetration in solid tumors via nanomedicine: Evaluation models, strategies and perspectives

Bioactive Materials, Journal Year: 2023, Volume and Issue: 32, P. 445 - 472

Published: Oct. 26, 2023

Effective tumor treatment depends on optimizing drug penetration and accumulation in tissue while minimizing systemic toxicity. Nanomedicine has emerged as a key solution that addresses the rapid clearance of free drugs, but achieving deep into solid tumors remains elusive. This review discusses various strategies to enhance penetration, including manipulation microenvironment, exploitation both external internal stimuli, pioneering nanocarrier surface engineering, development innovative tactics for active penetration. One outstanding strategy is organelle-affinitive transfer, which exploits unique properties specific cell organelles heralds potentially transformative approach transcellular transfer Rigorous models are essential evaluate efficacy these strategies. The patient-derived xenograft (PDX) model gaining traction bridge between laboratory discovery clinical application. However, journey from bench bedside nanomedicines fraught with challenges. Future efforts should prioritize deepening our understanding nanoparticle-tumor interactions, re-evaluating EPR effect, exploring novel nanoparticle transport mechanisms.

Language: Английский

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Metformin-based nanomedicines for reprogramming tumor immune microenvironment

Theranostics, Journal Year: 2024, Volume and Issue: 15(3), P. 993 - 1016

Published: Dec. 2, 2024

Immunotherapy has transformed current cancer management, and it achieved significant progress over last decades. However, an immunosuppressive tumor microenvironment (TME) diminishes the effectiveness of immunotherapy by suppressing activity immune cells facilitating immune-evasion. Adenosine monophosphate-activated protein kinase (AMPK), a key modulator cellular energy metabolism homeostasis, gained growing attention in anti-tumor immunity. Metformin is usually considered as cornerstone diabetes its role activating AMPK pathway also been extensively explored therapy although findings on remain inconsistent. nanomedicine formulation found to hold potential reprogramming TME through immunometabolic modulation both cells. This review elaborates foundation via metformin-based nanomedicines, offering valuable insights for next generation therapy.

Language: Английский

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