Engineering Macrophages for Cancer Immunotherapy and Drug Delivery

Advanced Materials, Journal Year: 2020, Volume and Issue: 32(40)

Published: Aug. 28, 2020

Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while anti-inflammatory M2 such as tumor-associated (TAMs) promote growth invasion. Modulating the immune microenvironment through engineering is efficacious therapy. target cancerous cells and, therefore, be used drug carriers for Herein, strategies to engineer immunotherapy, inhibition of macrophage recruitment, depletion TAMs, reprograming blocking CD47-SIRPα pathway, are discussed. Further, recent advances delivery using macrophages, macrophage-derived exosomes, macrophage-membrane-coated nanoparticles elaborated. Overall, there still significant room macrophage-mediated modulation delivery, which will further enhance current therapies against various malignant solid tumors, including drug-resistant tumors metastatic tumors.

Language: Английский

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Cellular backpacks for macrophage immunotherapy

Science Advances, Journal Year: 2020, Volume and Issue: 6(18)

Published: April 29, 2020

Adoptive cell transfers have emerged as a disruptive approach to treat disease in manner that is more specific than using small-molecule drugs; however, unlike traditional drugs, cells are living entities can alter their function response environmental cues. In the present study, we report an engineered particle referred "backpack" robustly adhere macrophage surfaces and regulate cellular phenotypes vivo. Backpacks evade phagocytosis for several days release cytokines continuously guide polarization of macrophages toward antitumor phenotypes. We demonstrate these durable, even strongly immunosuppressive environment murine breast cancer model. Conserved led reduced metastatic burdens slowed tumor growths compared with those mice treated equal dose free cytokine. Overall, studies highlight new pathway control maintain adoptive immunotherapies.

Language: Английский

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Responsive Exosome Nano‐bioconjugates for Synergistic Cancer Therapy

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 59(5), P. 2018 - 2022

Published: Nov. 20, 2019

Abstract Exosomes hold great potential in therapeutic development. However, native exosomes usually induce insufficient effects vivo and simply act as drug delivery vehicles. Herein, we synthesize responsive exosome nano‐bioconjugates for cancer therapy. Azide‐modified derived from M1 macrophages are conjugated with dibenzocyclooctyne‐modified antibodies of CD47 SIRPα (aCD47 aSIRPα) through pH‐sensitive linkers. After systemic administration, the can actively target tumors specific recognition between aCD47 on tumor cell surface. In acidic microenvironment, benzoic‐imine bonds cleaved to release aSIRPα that can, respectively, block CD47, leading abolished “don't eat me” signaling improved phagocytosis macrophages. Meanwhile, effectively reprogram pro‐tumoral M2 anti‐tumoral M1.

Language: Английский

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Tailoring Materials for Modulation of Macrophage Fate

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(12)

Published: Feb. 9, 2021

Human immune system acts as a pivotal role in the tissue homeostasis and disease progression. Immunomodulatory biomaterials that can manipulate innate immunity adaptive hold great promise for broad range of prophylactic therapeutic purposes. This review is focused on design strategies principles immunomodulatory from standpoint materials science to regulate macrophage fate, such activation, polarization, adhesion, migration, proliferation, secretion. It offers comprehensive survey discussion tunability material designs regarding physical, chemical, biological, dynamic cues modulating response. The tailorable encompasses surface properties, topography, mechanics, composition, dynamics. representative immunoengineering applications selected herein demonstrate how macrophage-immunomodulating are being exploited cancer immunotherapy, infection regeneration, inflammation resolution, vaccination. A perspective future research directions immunoregulatory also provided.

Language: Английский

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Recent Advances in Glucose‐Oxidase‐Based Nanocomposites for Tumor Therapy

Small, Journal Year: 2019, Volume and Issue: 15(51)

Published: Nov. 20, 2019

Abstract Glucose oxidase (GOx) can react with intracellular glucose and oxygen (O 2 ) to produce hydrogen peroxide (H O gluconic acid, which cut off the nutrition source of cancer cells consequently inhibit their proliferation. Therefore, GOx is recognised as an ideal endogenous oxido‐reductase for starvation therapy. This process further regulate tumor microenvironment by increasing hypoxia acidity. Thus, offers new possibilities elaborate design multifunctional nanocomposites However, natural expensive prepare purify exhibits immunogenicity, short in vivo half‐life, systemic toxicity. Furthermore, highly prone degrade after exposure biological conditions. These intrinsic shortcomings will undoubtedly limit its biomedical applications. Accordingly, some nanocarriers be used protect from surrounding environment, thus controlling or preserving activity. A variety including hollow mesoporous silica nanoparticles, metal–organic frameworks, organic polymers, magnetic nanoparticles are summarized construction GOx‐based multimodal synergistic In addition, current challenges promising developments this area highlighted.

Language: Английский

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Cytomembrane nanovaccines show therapeutic effects by mimicking tumor cells and antigen presenting cells

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: July 19, 2019

Most cancer vaccines are unsuccessful in eliciting clinically relevant effects. Without using exogenous antigens and adoptive cells, we show a concept of utilizing biologically reprogrammed cytomembranes the fused cells (FCs) derived from dendritic (DCs) as tumor vaccines. The fusion immunologically interrelated two types results strong expression whole antigen complexes immunological co-stimulatory molecules on (FMs), allowing nanoparticle-supported FM (NP@FM) to function like presenting (APCs) for T cell immunoactivation. Moreover, tumor-antigen bearing NP@FM can be bio-recognized by DCs induce DC-mediated combination these immunoactivation pathways offers powerful antitumor immunoresponse. Through mimicking both APCs this cytomembrane vaccine strategy develop various toward multiple provide chances accommodating diverse functions originating supporters.

Language: Английский

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Epigenetics-Based Tumor Cells Pyroptosis for Enhancing the Immunological Effect of Chemotherapeutic Nanocarriers

Nano Letters, Journal Year: 2019, Volume and Issue: 19(11), P. 8049 - 8058

Published: Sept. 27, 2019

Pyroptosis is a lytic and inflammatory form of programmed cell death could be induced by chemotherapy drugs via caspase-3 mediation. However, the key protein gasdermin E (GSDME, translated DFNA5 gene) during caspase-3-mediated pyroptosis process absent in most tumor cells because hypermethylation (deafness autosomal dominant 5) gene. Here, we develop strategy combining decitabine (DAC) with nanodrugs to trigger epigenetics, further enhancing immunological effect chemotherapy. DAC pre-performed specific tumor-bearing mice for demethylation gene cells. Subsequently, commonly used tumor-targeting nanoliposome loaded cisplatin (LipoDDP) administrate activating pathway pyroptosis. Experiments demonstrate that reversal GSDME silencing achieved facilitates occurrence According anti-tumor activities, anti-metastasis results, inhibition recurrence, this pyroptosis-based enhances effects also provides an important insight into immunotherapy.

Language: Английский

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Tumor-associated macrophages in cancer: recent advancements in cancer nanoimmunotherapies

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Feb. 19, 2022

Abstract Cancer immunotherapy has emerged as a novel cancer treatment, although recent trials have produced suboptimal outcomes, with durable responses seen only in small number of patients. The tumor microenvironment (TME) been shown to be responsible for immune escape and therapy failure. vital component the TME is tumor-associated macrophages (TAMs), which are usually associated poor prognosis drug resistance, including immunotherapies, promising targets immunotherapy. Recently, nanoparticles, because their unique physicochemical characteristics, crucial translational moieties tackling tumor-promoting TAMs that amplify sensitize tumors immunotherapies safe effective manner. In this review, we mainly described current potential nanomaterial-based therapeutic strategies target TAMs, restricting survival, inhibiting recruitment functionally repolarizing tumor-supportive antitumor type. understanding origin polarization role progression prognostic significance was also discussed review. We highlighted evolution chimeric antigen receptor (CAR)-macrophage cell therapy.

Language: Английский

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Recent applications of immunomodulatory biomaterials for disease immunotherapy

Exploration, Journal Year: 2022, Volume and Issue: 2(6)

Published: May 23, 2022

Immunotherapy is used to regulate systemic hyperactivation or hypoactivation treat various diseases. Biomaterial-based immunotherapy systems can improve therapeutic effects through targeted drug delivery, immunoengineering, etc. However, the immunomodulatory of biomaterials themselves cannot be neglected. In this review, we outline with functions discovered in recent years and their applications disease treatment. These inflammation, tumors, autoimmune diseases by regulating immune cell function, exerting enzyme-like activity, neutralizing cytokines, The prospects challenges biomaterial-based modulation are also discussed.

Language: Английский

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Recent Advances in Engineered Materials for Immunotherapy‐Involved Combination Cancer Therapy

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(31)

Published: May 28, 2021

Abstract Immunotherapy that can activate immunity or enhance the immunogenicity of tumors has emerged as one most effective methods for cancer therapy. Nevertheless, single‐mode immunotherapy is still confronted with several critical challenges, such low immune response, tumor infiltration, and complex immunosuppression microenvironment. Recently, combination other therapeutic modalities a powerful strategy to augment outcome in fighting against cancer. In this review, recent research advances chemotherapy, phototherapy, radiotherapy, sonodynamic therapy, metabolic microwave thermotherapy are summarized. Critical challenges future direction immunotherapy‐based also discussed.

Language: Английский

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