Nature Biomedical Engineering最新文献_第10页

Author Correction: Thermally sentient bionic limbs 作者更正：热敏仿生肢体。

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-03-11 DOI: 10.1038/s41551-024-01196-5

Max Ortiz-Catalan

引用次数: 0

Severely polarized extracellular acidity around tumour cells 肿瘤细胞周围细胞外酸性严重分化

IF 26.8 1区医学

Nature Biomedical Engineering Pub Date : 2024-03-04 DOI: 10.1038/s41551-024-01178-7

Qiang Feng, Zachary Bennett, Anthony Grichuk, Raymundo Pantoja, Tongyi Huang, Brandon Faubert, Gang Huang, Mingyi Chen, Ralph J. DeBerardinis, Baran D. Sumer, Jinming Gao

{"title":"Severely polarized extracellular acidity around tumour cells","authors":"Qiang Feng, Zachary Bennett, Anthony Grichuk, Raymundo Pantoja, Tongyi Huang, Brandon Faubert, Gang Huang, Mingyi Chen, Ralph J. DeBerardinis, Baran D. Sumer, Jinming Gao","doi":"10.1038/s41551-024-01178-7","DOIUrl":"10.1038/s41551-024-01178-7","url":null,"abstract":"Extracellular pH impacts many molecular, cellular and physiological processes, and hence is tightly regulated. Yet, in tumours, dysregulated cancer cell metabolism and poor vascular perfusion cause the tumour microenvironment to become acidic. Here by leveraging fluorescent pH nanoprobes with a transistor-like activation profile at a pH of 5.3, we show that, in cancer cells, hydronium ions are excreted into a small extracellular region. Such severely polarized acidity (pH <5.3) is primarily caused by the directional co-export of protons and lactate, as we show for a diverse panel of cancer cell types via the genetic knockout or inhibition of monocarboxylate transporters, and also via nanoprobe activation in multiple tumour models in mice. We also observed that such spot acidification in ex vivo stained snap-frozen human squamous cell carcinoma tissue correlated with the expression of monocarboxylate transporters and with the exclusion of cytotoxic T cells. Severely spatially polarized tumour acidity could be leveraged for cancer diagnosis and therapy. Hydronium ions bordering cancer cells are highly concentrated into a small extracellular region, and in tumour tissue such severely polarized acidity correlates with the expression of monocarboxylate transporters and with the exclusion of cytotoxic T cells.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":26.8,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140026590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neutrophils bearing adhesive polymer micropatches as a drug-free cancer immunotherapy 中性粒细胞粘附聚合物微补片作为一种无药癌症免疫疗法。

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-02-29 DOI: 10.1038/s41551-024-01180-z

Ninad Kumbhojkar, Supriya Prakash, Tatsuya Fukuta, Kwasi Adu-Berchie, Neha Kapate, Rocky An, Solomina Darko, Vineeth Chandran Suja, Kyung Soo Park, Alexander P. Gottlieb, Michael Griffith Bibbey, Malini Mukherji, Lily Li-Wen Wang, David J. Mooney, Samir Mitragotri

{"title":"Neutrophils bearing adhesive polymer micropatches as a drug-free cancer immunotherapy","authors":"Ninad Kumbhojkar, Supriya Prakash, Tatsuya Fukuta, Kwasi Adu-Berchie, Neha Kapate, Rocky An, Solomina Darko, Vineeth Chandran Suja, Kyung Soo Park, Alexander P. Gottlieb, Michael Griffith Bibbey, Malini Mukherji, Lily Li-Wen Wang, David J. Mooney, Samir Mitragotri","doi":"10.1038/s41551-024-01180-z","DOIUrl":"10.1038/s41551-024-01180-z","url":null,"abstract":"Tumour-associated neutrophils can exert antitumour effects but can also assume a pro-tumoural phenotype in the immunosuppressive tumour microenvironment. Here we show that neutrophils can be polarized towards the antitumour phenotype by discoidal polymer micrometric ‘patches’ that adhere to the neutrophils’ surfaces without being internalized. Intravenously administered micropatch-loaded neutrophils accumulated in the spleen and in tumour-draining lymph nodes, and activated splenic natural killer cells and T cells, increasing the accumulation of dendritic cells and natural killer cells. In mice bearing subcutaneous B16F10 tumours or orthotopic 4T1 tumours, intravenous injection of the micropatch-loaded neutrophils led to robust systemic immune responses, a reduction in tumour burden and improvements in survival rates. Micropatch-activated neutrophils combined with the checkpoint inhibitor anti-cytotoxic T-lymphocyte-associated protein 4 resulted in strong inhibition of the growth of B16F10 tumours, and in complete tumour regression in one-third of the treated mice. Micropatch-loaded neutrophils could provide a potent, scalable and drug-free approach for neutrophil-based cancer immunotherapy. The intravenous injection of neutrophils bearing discoidal polymer microscale ‘patches’ on their surfaces reduces tumour burden in mice owing to the patch-induced polarization of the neutrophils towards an antitumour phenotype.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How to appeal well 如何做好上诉工作

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-02-21 DOI: 10.1038/s41551-024-01182-x

引用次数: 0

Small-molecule-mediated control of the anti-tumour activity and off-tumour toxicity of a supramolecular bispecific T cell engager 小分子介导控制超分子双特异性 T 细胞吸引剂的抗肿瘤活性和瘤外毒性。

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-02-20 DOI: 10.1038/s41551-023-01147-6

Ningqiang Gong, Xuexiang Han, Lulu Xue, Margaret M. Billingsley, Xisha Huang, Rakan El-Mayta, Jingya Qin, Neil C. Sheppard, Carl H. June, Michael J. Mitchell

{"title":"Small-molecule-mediated control of the anti-tumour activity and off-tumour toxicity of a supramolecular bispecific T cell engager","authors":"Ningqiang Gong, Xuexiang Han, Lulu Xue, Margaret M. Billingsley, Xisha Huang, Rakan El-Mayta, Jingya Qin, Neil C. Sheppard, Carl H. June, Michael J. Mitchell","doi":"10.1038/s41551-023-01147-6","DOIUrl":"10.1038/s41551-023-01147-6","url":null,"abstract":"The broader clinical use of bispecific T cell engagers for inducing anti-tumour toxicity is hindered by their on-target off-tumour toxicity and the associated neurotoxicity and cytokine-release syndrome. Here we show that the off-tumour toxicity of a supramolecular bispecific T cell engager binding to the T cell co-receptor CD3 and to the human epidermal growth factor receptor 2 on breast tumour cells can be halted by disengaging the T cells from the tumour cells via the infusion of the small-molecule drug amantadine, which disassembles the supramolecular aggregate. In mice bearing human epidermal growth factor receptor 2-expressing tumours and with a human immune system, high intravenous doses of such a ‘switchable T cell nanoengager’ elicited strong tumour-specific adaptive immune responses that prevented tumour relapse, while the infusion of amantadine restricted off-tumour toxicity, cytokine-release syndrome and neurotoxicity. Supramolecular chemistry may be further leveraged to control the anti-tumour activity and off-tumour toxicity of bispecific antibodies. The off-tumour toxicity of a supramolecular bispecific T cell engager can be halted by disengaging T cells from the tumour cells via the disassembly of the supramolecular aggregate through the infusion of the small-molecule drug amantadine.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Screening oral drugs for their interactions with the intestinal transportome via porcine tissue explants and machine learning 通过猪组织外植体和机器学习筛选口服药物与肠道转运体的相互作用。

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-02-20 DOI: 10.1038/s41551-023-01128-9

Yunhua Shi, Daniel Reker, James D. Byrne, Ameya R. Kirtane, Kaitlyn Hess, Zhuyi Wang, Natsuda Navamajiti, Cameron C. Young, Zachary Fralish, Zilu Zhang, Aaron Lopes, Vance Soares, Jacob Wainer, Thomas von Erlach, Lei Miao, Robert Langer, Giovanni Traverso

{"title":"Screening oral drugs for their interactions with the intestinal transportome via porcine tissue explants and machine learning","authors":"Yunhua Shi, Daniel Reker, James D. Byrne, Ameya R. Kirtane, Kaitlyn Hess, Zhuyi Wang, Natsuda Navamajiti, Cameron C. Young, Zachary Fralish, Zilu Zhang, Aaron Lopes, Vance Soares, Jacob Wainer, Thomas von Erlach, Lei Miao, Robert Langer, Giovanni Traverso","doi":"10.1038/s41551-023-01128-9","DOIUrl":"10.1038/s41551-023-01128-9","url":null,"abstract":"In vitro systems that accurately model in vivo conditions in the gastrointestinal tract may aid the development of oral drugs with greater bioavailability. Here we show that the interaction profiles between drugs and intestinal drug transporters can be obtained by modulating transporter expression in intact porcine tissue explants via the ultrasound-mediated delivery of small interfering RNAs and that the interaction profiles can be classified via a random forest model trained on the drug–transporter relationships. For 24 drugs with well-characterized drug–transporter interactions, the model achieved 100% concordance. For 28 clinical drugs and 22 investigational drugs, the model identified 58 unknown drug–transporter interactions, 7 of which (out of 8 tested) corresponded to drug-pharmacokinetic measurements in mice. We also validated the model’s predictions for interactions between doxycycline and four drugs (warfarin, tacrolimus, digoxin and levetiracetam) through an ex vivo perfusion assay and the analysis of pharmacologic data from patients. Screening drugs for their interactions with the intestinal transportome via tissue explants and machine learning may help to expedite drug development and the evaluation of drug safety. A machine-learning model trained on interactions between oral drugs and intestinal drug transporters obtained by modulating their expression in intact porcine tissue can be used to predict drug–transporter and drug–drug interactions.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular vesicles incorporating retrovirus-like capsids for the enhanced packaging and systemic delivery of mRNA into neurons 细胞外囊泡含有类似逆转录病毒的囊壳，可增强 mRNA 的包装和向神经元的系统输送。

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-02-19 DOI: 10.1038/s41551-023-01150-x

Wenchao Gu, Sijin Luozhong, Simian Cai, Ketaki Londhe, Nadine Elkasri, Robert Hawkins, Zhefan Yuan, Kai Su-Greene, Yujie Yin, Margaret Cruz, Yu-Wei Chang, Patrick McMullen, Chunyan Wu, Changwoo Seo, Akash Guru, Wenting Gao, Tara Sarmiento, Chris Schaffer, Nozomi Nishimura, Richard Cerione, Qiuming Yu, Melissa Warden, Robert Langer, Shaoyi Jiang

{"title":"Extracellular vesicles incorporating retrovirus-like capsids for the enhanced packaging and systemic delivery of mRNA into neurons","authors":"Wenchao Gu, Sijin Luozhong, Simian Cai, Ketaki Londhe, Nadine Elkasri, Robert Hawkins, Zhefan Yuan, Kai Su-Greene, Yujie Yin, Margaret Cruz, Yu-Wei Chang, Patrick McMullen, Chunyan Wu, Changwoo Seo, Akash Guru, Wenting Gao, Tara Sarmiento, Chris Schaffer, Nozomi Nishimura, Richard Cerione, Qiuming Yu, Melissa Warden, Robert Langer, Shaoyi Jiang","doi":"10.1038/s41551-023-01150-x","DOIUrl":"10.1038/s41551-023-01150-x","url":null,"abstract":"The blood–brain barrier (BBB) restricts the systemic delivery of messenger RNAs (mRNAs) into diseased neurons. Although leucocyte-derived extracellular vesicles (EVs) can cross the BBB at inflammatory sites, it is difficult to efficiently load long mRNAs into the EVs and to enhance their neuronal uptake. Here we show that the packaging of mRNA into leucocyte-derived EVs and the endocytosis of the EVs by neurons can be enhanced by engineering leucocytes to produce EVs that incorporate retrovirus-like mRNA-packaging capsids. We transfected immortalized and primary bone-marrow-derived leucocytes with DNA or RNA encoding the capsid-forming activity-regulated cytoskeleton-associated (Arc) protein as well as capsid-stabilizing Arc 5’-untranslated-region RNA elements. These engineered EVs inherit endothelial adhesion molecules from donor leukocytes, recruit endogenous enveloping proteins to their surface, cross the BBB, and enter the neurons in neuro-inflammatory sites. Produced from self-derived donor leukocytes, the EVs are immunologically inert, and enhanced the neuronal uptake of the packaged mRNA in a mouse model of low-grade chronic neuro-inflammation. The delivery of mRNAs into neurons at inflammatory sites in vivo can be enhanced by engineering leucocytes to produce extracellular vesicles incorporating mRNA-packaging retrovirus-like capsids.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":28.1,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: Generation of T-cell-receptor-negative CD8αβ-positive CAR T cells from T-cell-derived induced pluripotent stem cells. 作者更正：从 T 细胞衍生的诱导多能干细胞中生成 T 细胞受体阴性的 CD8αβ 阳性 CAR T 细胞。

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-02-12 DOI: 10.1038/s41551-024-01181-y

Sjoukje J C van der Stegen, Pieter L Lindenbergh, Roseanna M Petrovic, Hongyao Xie, Mame P Diop, Vera Alexeeva, Yuzhe Shi, Jorge Mansilla-Soto, Mohamad Hamieh, Justin Eyquem, Annalisa Cabriolu, Xiuyan Wang, Ramzey Abujarour, Tom Lee, Raedun Clarke, Bahram Valamehr, Maria Themeli, Isabelle Riviere, Michel Sadelain

引用次数: 0

Author Correction: High-throughput screening of genetic and cellular drivers of syncytium formation induced by the spike protein of SARS-CoV-2 作者更正：高通量筛选SARS-CoV-2尖峰蛋白诱导合胞体形成的基因和细胞驱动因素。

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-01-24 DOI: 10.1038/s41551-024-01177-8

Charles W. F. Chan, Bei Wang, Lang Nan, Xiner Huang, Tianjiao Mao, Hoi Yee Chu, Cuiting Luo, Hin Chu, Gigi C. G. Choi, Ho Cheung Shum, Alan S. L. Wong

引用次数: 0

Hail the AI journal editor 人工智能期刊编辑万岁

IF 28.1 1区医学

Nature Biomedical Engineering Pub Date : 2024-01-22 DOI: 10.1038/s41551-024-01176-9

引用次数: 0