No abstract

Cancer stem cells (CSCs) have been identified in almost all cancers and give rise to metastases and can also act as a reservoir of cancer cells that may cause a relapse after surgery, radiation, or chemotherapy. Thus they are obvious targets in therapeutic approaches and also a great challenge in cancer treatment. The threat presented by CSCs lies in their unlimited proliferative ability and multidrug resistance. These findings have necessitated an effective novel strategy to target CSCs for cancer treatment. Nanomaterials are on the route to providing novel methods in cancer therapies. Although, there have been a large number of excellent work in the field of targeted cancer therapy, it remains an open question how nanomaterials can meet future demands for targeting and eradicating of CSCs. In this review, we summarized recent and highlighted future prospects for targeting CSCs for cancer therapies by using a variety of nanomaterials.

Microfluidics have become an enabling technology for point-of-care and personalized diagnostics. Desirable capabilities of microfluidics-based diagnostic devices include simplicity, portability, low cost and the performance of multiplexed and quantitative measurements, ideally in a high-throughput format. Here we present the multiplexed volumetric bar-chart chip (V-Chip), which integrates all these capabilities in one device. A key feature of the V-Chip is that quantitative results are displayed as bar charts directly on the device—without the need for optical instruments or any data processing or plotting steps. This is achieved by directly linking oxygen production by catalase, which is proportional to the concentration of the analyte, with the displacement of ink along channels on the device. We demonstrate the rapid quantification of protein biomarkers in diverse clinical samples with the V-Chip. The development of the V-Chip thus opens up the possibility of greatly simplified point-of-care and personalized diagnostics.

Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma. Solid tumors including melanoma, breast cancer and sarcoma offer great promise in CAR-T cell research and development. CD19 CAR-T cell is most commonly used, and other targets, including CD20, CD30, CD38 and CD138 are being studied. Although this novel therapy is promising, there are several disadvantages. In this review we discuss the applications of CAR-T cells in different hematological malignancies, and pave a way for future improvement on the effectiveness and persistence of these adoptive cell therapies.

Extracellular vesicles (EVs) hold great promise for transporting CRISPR–Cas9 RNA-guided endonucleases (RNP) throughout the body. However, the cell-selective delivery of EVs is still a challenge. Here, we designed valency-controlled tetrahedral DNA nanostructures (TDNs) conjugated with DNA aptamer, and loaded the valency-controlled TDNs on EV surface via cholesterol anchoring for specific cell targeting. The targeting efficacy of different ratios of aptamer/cholesterol from 1:3 to 3:1 in TDNs on decorating EVs was investigated. TDNs with one aptamer and three cholesterol anchors (TDN1) efficiently facilitated the tumor-specific accumulation of the EVs in cultured HepG2 cells and human primary liver cancer-derived organoids, as well as xenograft tumor models. The intracellular delivery of RNP by TDN1-EVs successfully realized its subsequent genome editing, leading to the downregulation of GFP or WNT10B in specific cells. This system was ultimately applied to reduce the protein expression of WNT10B, which presented remarkable tumor growth inhibition in vitro, ex vivo and in vivo, and could be extended to other therapeutic targets. The present study provides a platform for the directional display of aptamer on surface labeling and the EVs-based Cas9 delivery, which provides a meaningful idea for future cell-selective gene editing.