Tissue Niche Miniature of Glioblastoma Patient Treated with Nano‐Awakeners to Induce Suicide of Cancer Stem Cells

Abstract

Patient-specific cancer therapies can evolve by vitalizing the mother tissue-like cancer niche, cellular profile, genetic signature, and drug responsiveness. This evolution has enabled the elucidation of a key mechanism along with development of the mechanism-driven therapy. After surgical treatment, glioblastoma (GBM) patients require prompt therapy within 14 days in a patient-specific manner. Hence, this study approaches direct culture of GBM patient tissue (1 mm diameter) in a microchannel network chip. Cancer vasculature-mimetic perfusion can support the preservation of the mother tissue-like characteristic signatures and microenvironment. When temozolomide and radiation are administered within 1 day, the responsiveness of the tissue in the chip reflected the clinical outcomes, thereby overcoming the time-consuming process of cell and organoid culture. When the tissue chip culture is continued, the intact GBM signature gets lost, and the outward migration of stem cells from the tissue origin increases, indicating a leaving-home effect on the family dismantle. Nanovesicle production using GBM stem cells enables self-chasing of the cells that escape the temozolomide effect owing to quiescence. The anti-PTPRZ1 peptide display and temozolomide loading to nanovesicles awakes cancer stem cells from the quiescent stage to death. This study suggests a GBM clinic-driven avatar platform and mechanism-learned nanotherapy for translation.

Protein Tyrosine Phosphatase Receptor Zeta 1 as a Potential Target in Cancer Therapy and Diagnosis

“…Besides developing drugs that target PTPRZ1 to inhibit its signaling, PTPRZ1 has also been considered as a cell membrane molecule exploited to target GBM stem cells with cytotoxic chemotherapeutics. In a study using patient-derived GBM tissues cultured in a microchannel network chip, resistance to temozolomide and radiation is observed, similar to what is observed in GBM patients, and can be overcome by nanovesicles displaying an anti-PTPRZ1 peptide and loaded with temozolomide [127]. In a similar approach, a selfassembled hybrid micelle that can cross the blood-brain barrier, and simultaneously target M2-like tumor-associated macrophages by a specific peptide and GBM stem cells by an anti-PTPRZ1 antibody, was developed as a nanocarrier to deliver the chemotherapeutic agent doxorubicin to the GBM tissue.…”

Intercellular aspirin hand-over with dual therapies by liposome-loaded monocytes

“…So far, the technical development has been rst focused on the advanced design of delivery vehicles by adding pH 27 , reactive oxygen species (ROS) 28 , or enzyme-responsive properties 29 . Second, pin-point targeting has been approached by relying on unique molecule-molecule interactions 30,31 . Third, a speci c condition-mediated exertion of effect has been strategized in response to activation of in ammatory 32,33 , immune 13 , or cancer cells 34 .…”

Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue

“…For the microchannel networks, microfibers were produced by spinning a PCL-PVAc-PEG copolymer (Soluplus®, 30446233; BASF, Ludwigshafen, Germany) dissolved in a 66% w v −1 MeOH solution using a custom device. The diameter of the fibers was adjusted by varying the rotational speed (140-176 g) of the spinning device 42,[44][45][46] . Subsequently, the fibers were placed in a polydimethylsiloxane (PDMS, 31-000810-02; Dow corning, Midland, MI, USA) mold measuring 2 × 2 × 0.5 cm at a density ranging from 0 to 3 mg mL −1 .…”