Cancer

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The sustained release of both hydrophilic and hydrophobic immunomodulators for metastatic melanoma by nanoscale liposomal polymeric gels administered intratumorally or systemically is demonstrated. It is also shown that such a co-delivery approach delays tumour growth and increases the survival of tumour-bearing mice, and that its efficacy results from the activation of both innate and adaptative immune responses.

Conventional methods for the selection of tumorigenic cells from cancer cell lines rely on stem-cell markers. It is now shown that soft fibrin gels promote the growth of colonies of tumorigenic cells from single cancer cells from mouse or human cancer cell lines, and that as few as ten fibrin-cultured cells can lead to the formation of tumours in mice more efficiently than marker-selected cells.

A nanocarrier—synthesized by the fusion of liposomes to spherical, nanoporous silica particles and subsequent modification of the lipid bilayer with targeting peptides and fusogenic peptides—shows the targeted delivery and controlled release of chemically diverse multicomponent cargos within the cytosol of certain cancer cells.