News & Views |
Featured
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Article |
Cell volume expansion and local contractility drive collective invasion of the basement membrane in breast cancer
Forces resulting from global cell volume expansion and local cell contractions distort the basement membrane of an in vitro three-dimensional model of breast cancer, to promote collective cell invasion that precedes metastasis.
- Julie Chang
- , Aashrith Saraswathibhatla
- & Ovijit Chaudhuri
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News & Views |
Lymphatics drain nanoparticles from tumours
Lymphatic vessels within and near to tumours facilitate nanoparticle transport out of tumours, with ramifications in the design and implementation of next-generation clinical cancer nanomedicines.
- Meghan J. O’Melia
- & Susan N. Thomas
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Article |
The exit of nanoparticles from solid tumours
Nanoparticle retention inside tumours has been associated with lymphatic vessel collapse. It is now shown that nanoparticles exit from solid tumours through lymphatic vessels in or surrounding the tumour by a nanoparticle-size-dependent mechanism.
- Luan N. M. Nguyen
- , Zachary P. Lin
- & Warren C. W. Chan
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News & Views |
Unjamming tumour cell invasion through cGAS–STING
Locally confined epithelial malignancies undergo a phase transition from a solid-like to liquid-like state, a process called unjamming, where associated chronic intracellular strain causes nuclear envelope rupture, leading to the emergence of pro-metastatic traits due to cGAS–STING pathway activation.
- Matthew Deyell
- & Samuel F. Bakhoum
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News & Views |
Exosome-disrupting peptides for cancer immunotherapy
A curvature-sensing peptide is used to disrupt exosomes for enhanced cancer immunotherapy.
- Ningqiang Gong
- , Alex G. Hamilton
- & Michael J. Mitchell
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Article |
Curvature-sensing peptide inhibits tumour-derived exosomes for enhanced cancer immunotherapy
A curvature-sensing antiviral peptide is repurposed to disrupt tumour-derived exosomes and used in combination with immune checkpoint blockade cancer therapy.
- Sol Shin
- , Hyewon Ko
- & Jae Hyung Park
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News & Views |
A synthetic tumour microenvironment
A bioengineered model incorporating a synthetic extracellular matrix recapitulates the lymphoid tumour microenvironment, making it a valuable tool for drug testing and designing personalized therapies.
- Akhilesh K. Gaharwar
- & Irtisha Singh
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Article |
Combinatorial treatment rescues tumour-microenvironment-mediated attenuation of MALT1 inhibitors in B-cell lymphomas
A hydrogel-based modular lymphoma organoid identifies how lymphoid microenvironment cues dampen the effect of MALT1 inhibitors and informs effective combination therapies to rescue the treatment response
- Shivem B. Shah
- , Christopher R. Carlson
- & Ankur Singh
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Article
| Open AccessP-selectin-targeted nanocarriers induce active crossing of the blood–brain barrier via caveolin-1-dependent transcytosis
Targeting of tumour vasculature endothelial P-selectin promotes caveolin-1-mediated transcytosis for enhanced blood–brain barrier crossing of therapeutic nanoparticles against medulloblastoma.
- Daniel E. Tylawsky
- , Hiroto Kiguchi
- & Daniel A. Heller
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Article
| Open AccessTissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer
Tissue fluidification in invasive breast carcinoma is accompanied by mechanical stresses that compromise nuclear integrity and liberate DNA, resulting in the activation of a pro-inflammatory response that shape tumour evolution and progression.
- Emanuela Frittoli
- , Andrea Palamidessi
- & Giorgio Scita
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News & Views |
Synthetic scaffold for pancreatic organoids
A synthetic matrix recapitulates fundamental biological interactions of pancreatic cancer to facilitate the culture of mouse and human pancreatic organoids.
- Sohini Khan
- & Hervé Tiriac
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News & Views |
A ‘Swiss army knife’ probe for metastatic cancers
A nanosensor probe that combines a tumour-targeting peptide, a diagnostic reporter and an imaging contrast agent enables early diagnosis, precision imaging, disease stratification and downstream therapeutic response monitoring of metastatic cancer.
- Matthew Bogyo
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Article |
A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids
A synthetic hydrogel has been developed to mimic the physicochemical properties of pancreatic tissue and is shown to support the culture of pancreatic cancer organoids, revealing the role of laminin–integrin interactions in their growth.
- Christopher R. Below
- , Joanna Kelly
- & Claus Jørgensen
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Review Article |
Next-generation cancer organoids
This Review summarizes limitations in the current techniques used for patient-derived cancer organoid culture and highlights recent advancements and future opportunities for their standardization.
- Bauer L. LeSavage
- , Riley A. Suhar
- & Sarah C. Heilshorn
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Article |
Microenvironment-triggered multimodal precision diagnostics
Multimodal nanosensors have been developed to target and respond to hallmarks in the tumour microenvironment and provide both a non-invasive urinary monitoring tool and an on-demand positron emission tomography imaging agent to localize tumour metastasis and assess response to therapy.
- Liangliang Hao
- , Nazanin Rohani
- & Sangeeta N. Bhatia
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Perspective |
Obstacles and opportunities in a forward vision for cancer nanomedicine
This Perspective discusses biological barriers that have limited clinical translation of cancer nanomedicines and elaborates on new directions for the field that capitalize on a deeper understanding of the nano–bio interface.
- Irene de Lázaro
- & David J. Mooney
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News & Views |
Netrin-4 regulates stiffness and metastasis
The stiffness of the basement membrane is a determinant of the process of metastasis and patient survival. Netrin-4 is now shown to be a key regulator of the basement membrane stiffness.
- Patrick Mehlen
- & Laurent Fattet
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News & Views |
Nanodevices for cancer vaccination
An elaborate DNA origami tubular nanodevice encapsulating antigens and adjuvants protects mice from cancer through tumour-specific immunomodulation.
- Hongjun Li
- & Zhen Gu
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Article |
Basement membrane stiffness determines metastases formation
The basement membrane stiffness is shown to be a more dominant determinant than pore size in regulating cancer cell invasion, metastasis formation and patient survival. This stiffness is now known to be affected by the ratio of netrin-4 to laminin, with more netrin-4 leading to softer basement membranes.
- Raphael Reuten
- , Sina Zendehroud
- & Janine T. Erler
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Article |
Tumour-associated macrophages drive stromal cell-dependent collagen crosslinking and stiffening to promote breast cancer aggression
It is now shown that tumour-associated macrophages recruited early during tumour evolution stimulate stromal fibroblasts to express collagen crosslinking enzymes and that the stromal expression, particularly of lysyl hydroxylase 2, can predict survival in a patient cohort.
- Ori Maller
- , Allison P. Drain
- & Valerie M. Weaver
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News & Views |
Just dose it
A dose threshold of one trillion nanoparticles in mice has been discovered and is shown to be crucial for overwhelming the nanoparticle uptake kinetics of liver Kupffer cells and for ensuring efficient nanoparticle delivery into solid tumours upon intravenous administration.
- Twan Lammers
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News & Views |
Dendritic cell tracking and modulation
In situ metabolic labelling and targeted modulation of dendritic cells has been achieved using a hydrogel system in combination with covalent capture of antigens and adjuvants, facilitating improved tumour-specific immune response.
- Joshua M. Gammon
- & Christopher M. Jewell
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Article |
A DNA nanodevice-based vaccine for cancer immunotherapy
A DNA nanodevice vaccine has been developed and utilized to stimulate a tumour-specific cytotoxic T lymphocyte response in vivo, leading to the inhibition of tumour growth as well as prevention of metastasis.
- Shaoli Liu
- , Qiao Jiang
- & Baoquan Ding
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Review Article |
Somatic cell-derived organoids as prototypes of human epithelial tissues and diseases
This Review highlights approaches used to generate somatic cell-derived organoids for modelling epithelial tissue to understand disease progression and how they are employed in preclinical drug screening.
- Masayuki Fujii
- & Toshiro Sato
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Article |
The dose threshold for nanoparticle tumour delivery
Efficient nanoparticle delivery into tumours has been a challenge in the field. It is now shown that the efficiency can be improved substantially when the dose breaches a specific threshold.
- Ben Ouyang
- , Wilson Poon
- & Warren C. W. Chan
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News & Views |
Oncogenetic engagement with mechanosensing
Reprogramming normal cells into tumour precursors involves complex reconditioning of the tissue microenvironment. Cumulative integration of genetic drivers with extrinsic mechanical inputs is now shown to engage YAP/TAZ to rewire cell mechanics and initiate tumorigenic reprogramming.
- Sayan Chakraborty
- & Wanjin Hong
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Article |
Metabolic labeling and targeted modulation of dendritic cells
Dendritic cells concentrated in vivo within a hydrogel have been metabolically tagged with azido groups to enable tracking as well as delivery of antigens, adjuvants and cytokines, thereby facilitating targeted immunomodulation.
- Hua Wang
- , Miguel C. Sobral
- & David J. Mooney
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Article |
Reprogramming normal cells into tumour precursors requires ECM stiffness and oncogene-mediated changes of cell mechanical properties
Receptor tyrosine kinase (RTK)–Ras oncogenes have now been shown to reprogram normal primary human and mouse cells into tumour precursors by empowering cellular mechanotransduction, in a process requiring permissive extracellular-matrix rigidity and intracellular YAP/TAZ/Rac mechanical signalling sustained by activated oncogenes.
- Tito Panciera
- , Anna Citron
- & Stefano Piccolo
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News & Views |
Life and death agendas of actin filaments
Cancer cells have now been shown to lack rigidity-sensing due to alteration in cytoskeletal sensor proteins, but can be reversed from a transformed to a rigidity-dependent growth state by the sensor proteins, resulting in restoration of contractility and adhesion.
- Edna C. Hardeman
- & Peter W. Gunning
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News & Views |
Bringing order to the matrix
Aligned anisotropic organization of the extracellular matrix by fibroblasts has now been shown to depend on cell reorientation following collision, with the cell collision guidance dependent on the transcription factor, TFAP2C.
- Paolo P. Provenzano
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Article |
The entry of nanoparticles into solid tumours
The dominant mechanism of nanoparticle entry into solid tumours has now been shown to be an active trans-endothelial pathway rather than the currently established passive transport via inter-endothelial gaps.
- Shrey Sindhwani
- , Abdullah Muhammad Syed
- & Warren C. W. Chan
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Article |
Taxanes convert regions of perturbed microtubule growth into rescue sites
Anticancer drugs such as Taxol can affect microtubule dynamics and organization in cells. Direct visualization of the action of such drugs has shown that they can trigger local and cooperative changes in microtubule lattice and induce formation of stable microtubule regions that promote rescues.
- Ankit Rai
- , Tianyang Liu
- & Anna Akhmanova
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Article |
Stopping transformed cancer cell growth by rigidity sensing
A range of cancer cell types are shown to lack rigidity-sensing due to alteration in specific cytoskeletal sensor proteins and this sensing ability can be reversed from a transformed to a rigidity-dependent growth state by the sensor proteins, resulting in restoration of contractility and adhesion.
- Bo Yang
- , Haguy Wolfenson
- & Michael P. Sheetz
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News & Views |
Molecular basis for fluidization of cancer cells
A molecular pathway has been identified in the regulation of unjamming to overcome cancer cell migration and proliferation arrest leading to collective cell invasion.
- René Marc Mège
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Article |
Furin-mediated intracellular self-assembly of olsalazine nanoparticles for enhanced magnetic resonance imaging and tumour therapy
An anticancer agent, olsalazine, conjugated to a cell-penetrating peptide has been synthesized and shows the ability to self-assemble intracellularly by the tumour-associated enzyme furin, with the potential for tumour therapy and chemical exchange saturation transfer magnetic resonance imaging in vivo.
- Yue Yuan
- , Jia Zhang
- & Jeff W. M. Bulte
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Editorial |
Awards for manipulating technologies
The 2018 Nobel prizes in chemistry and medicine celebrate tools for engineering biological materials.
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Review Article |
Biomaterial-assisted targeted modulation of immune cells in cancer treatment
Immunotherapies have shown significant promise in cancer treatment. This Review discusses how a range of materials have been employed to enhance the effectiveness of these therapies by mediating their delivery and immunomodulatory activity.
- Hua Wang
- & David J. Mooney
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Feature |
Dendritic cells in cancer immunotherapy
Camille M. Le Gall, Jorieke Weiden, Loek J. Eggermont and Carl G. Figdor provide an overview of immunotherapeutics for cancer treatment that harness dendritic cells, their challenges in clinical use, and approaches employed to enhance their recruitment and activation to promote effective anti-tumour immunity.
- Camille M. Le Gall
- , Jorieke Weiden
- & Carl G. Figdor
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Feature |
Material aid for vaccines
Darrell Irvine provides an overview of the recent advances in materials science that have enabled the use of innovative natural and synthetic compounds in vaccine development capable of regulating the potency and safety of new vaccines progressing towards the clinic.
- Darrell Irvine
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Editorial |
Cells and materials in immunotherapy
As the interaction of the immune system with the tumour microenvironment becomes increasingly understood, more evidence indicates how immunotherapy can be employed to better eliminate cancers.
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Feature |
Adoptive T cell cancer therapy
Tumour heterogeneity and off-target toxicity are current challenges of cancer immunotherapy. Karine Dzhandzhugazyan, Per Guldberg and Alexei Kirkin discuss how epigenetic induction of tumour antigens in antigen-presenting cells may form the basis for multi-target therapies.
- Karine N. Dzhandzhugazyan
- , Per Guldberg
- & Alexei F. Kirkin
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News & Views |
Smart delivery of vaccines
A strategy to enhance antigen immunogenicity was developed by adsorption of polyethyleneimine on a mesoporous silica microrod vaccine for the presentation of tumour viruses and neoantigens, demonstrating their ability to drive anti-tumour immunity.
- Cornelis J. M. Melief
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News & Views |
Treasure trove for cancer medicine
Fragments of DNA that are derived from dead tumour cells and shed into a patient's blood have been utilized as biomarkers for the diagnosis and prognosis of liver cancer.
- Miljana Tanić
- & Stephan Beck
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Article |
Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma
Circulating tumour DNA is used as a biomarker for cancer diagnosis. Here, the authors identified a DNA methylation biomarker for hepatocellular carcinoma and developed diagnostic and prognostic models to predict specificity and survival of patients.
- Rui-hua Xu
- , Wei Wei
- & Kang Zhang
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News & Views |
Stemness shaped by curvature
Substrates with curved edges induce the reprogramming of cancer cells into a stem-cell-like phenotype.
- Bettina Weigelin
- & Peter Friedl
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Letter |
Interfacial geometry dictates cancer cell tumorigenicity
Experiments with engineered hydrogels show that the geometry of the interface at the perimeter of tumour tissue can guide cancer cells towards a stem-cell-like state.
- Junmin Lee
- , Amr A. Abdeen
- & Kristopher A. Kilian
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News & Views |
Roll-on scaffolds
A spool-and-ribbon cell-culture approach provides quick and easy access to the interior of engineered tumours for the analysis of cell responses to molecular gradients.
- Peter DelNero
- & Claudia Fischbach
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