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"Ebara, Mitsuhiro"
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Shape-memory surfaces for cell mechanobiology
Shape-memory polymers (SMPs) are a new class of smart materials, which have the capability to change from a temporary shape 'A' to a memorized permanent shape 'B' upon application of an external stimulus. In recent years, SMPs have attracted much attention from basic and fundamental research to industrial and practical applications due to the cheap and efficient alternative to well-known metallic shape-memory alloys. Since the shape-memory effect in SMPs is not related to a specific material property of single polymers, the control of nanoarchitecture of polymer networks is particularly important for the smart functions of SMPs. Such nanoarchitectonic approaches have enabled us to further create shape-memory surfaces (SMSs) with tunable surface topography at nano scale. The present review aims to bring together the exciting design of SMSs and the ever-expanding range of their uses as tools to control cell functions. The goal for these endeavors is to mimic the surrounding mechanical cues of extracellular environments which have been considered as critical parameters in cell fate determination. The untapped potential of SMSs makes them one of the most exciting interfaces of materials science and cell mechanobiology.
Journal Article
What are the emerging concepts and challenges in NANO? Nanoarchitectonics, hand-operating nanotechnology and mechanobiology
Most of us may mistakenly believe that sciences within the nano regime are a simple extension of what is observed in micrometer regions. We may be misled to think that nanotechnology is merely a far advanced version of microtechnology. These thoughts are basically wrong. For true developments in nanosciences and related engineering outputs, a simple transformation of technology concepts from micro to nano may not be perfect. A novel concept, nanoarchitectonics, has emerged in conjunction with well-known nanotechnology. In the first part of this review, the concept and examples of nanoarchitectonics will be introduced. In the concept of nanoarchitectonics, materials are architected through controlled harmonized interactions to create unexpected functions. The second emerging concept is to control nano-functions by easy macroscopic mechanical actions. To utilize sophisticated forefront science in daily life, high-tech-driven strategies must be replaced by low-tech-driven strategies. As a required novel concept, hand-operation nanotechnology can control nano and molecular systems through incredibly easy action. Hand-motion-like macroscopic mechanical motions will be described in this review as the second emerging concept. These concepts are related bio-processes that create the third emerging concept, mechanobiology and related mechano-control of bio-functions. According to this story flow, we provide some incredible recent examples such as atom-level switches, operation of molecular machines by hand-like easy motions, and mechanical control of cell fate. To promote and activate science and technology based on these emerging concepts in nanotechnology, the contribution and participation of polymer scientists are crucial. We hope that some readers would have interests within what we describe.
This review tests you for survival in modern science and technology.Q1: Can we operate molecular machines by our hands?Ans: YES (Hand-Operating Nanotechnology)!Q2: Can we mechanically control life and bio-events?Ans: YES (Mechanobiology)!Q3: What comes after nanotechnology?Ans: It is definitely Nanoarchitectonics.
Journal Article
Correction: Mano et al. Fluidity of Poly (ε-Caprolactone)-Based Material Induces Epithelial-to-Mesenchymal Transition. Int. J. Mol. Sci. 2020, 21, 1757
In the original publication [...]
Journal Article
Influences of Crystallinity and Crosslinking Density on the Shape Recovery Force in Poly(ε-Caprolactone)-Based Shape-Memory Polymer Blends
Shape-memory polymers (SMPs) show great potential in various emerging applications, such as artificial muscles, soft actuators, and biomedical devices, owing to their unique shape recovery-induced contraction force. However, the factors influencing this force remain unclear. Herein, we designed a simple polymer blending system using a series of tetra-branched poly(ε-caprolactone)-based SMPs with long and short branch-chain lengths that demonstrate decreased crystallinity and increased crosslinking density gradients. The resultant polymer blends possessed mechanical properties manipulable across a wide range in accordance with the crystallinity gradient, such as stretchability (50.5–1419.5%) and toughness (0.62–130.4 MJ m−3), while maintaining excellent shape-memory properties. The experimental results show that crosslinking density affected the shape recovery force, which correlates to the SMPs’ energy storage capacity. Such a polymer blending system could provide new insights on how crystallinity and crosslinking density affect macroscopic thermal and mechanical properties as well as the shape recovery force of SMP networks, improving design capability for future applications.
Journal Article
Poly(ARTEMA), a novel artesunate-based polymer induces ferroptosis in breast cancer cells
Ferroptosis, a form of non-apoptotic cell death, is emerging as a promising strategy for cancer therapy. Artesunate (ART), an extract obtained from the traditional Chinese medicine Qinghaosu, has been shown to exhibit anti-cancer activity by inducing ferroptosis in cancer cells. While previous research has focused on incorporating ART monomer into drug delivery systems for enhanced cancer targeting, this study presents 2-methacryloyloxyethyl ART polymer (poly(ARTEMA)), a novel polymer synthesized from ART for the first time. Our goal was evaluation of poly(ARTEMA) anticancer potential on breast cancer cells. First, we synthesized ARTEMA using esterification followed by its polymerization using the reversible addition-fragmentation chain transfer (RAFT) polymerization method. We evaluated its mechanism of action, focusing on two key pathways: temperature-triggered singlet oxygen generation and ferrous ions (Fe
) release, both of which contribute to ferroptosis. Our results demonstrate that poly(ARTEMA) selectively generates singlet oxygen and Fe
due to the endoperoxide crosslinks, leading to cell death in breast cancer cells. We also investigated the anti-cancer potential of poly(ARTEMA) on breast cancer cells with and without a ferroptosis inhibitor. The IC
values were 125 µM for the MCF-7 cancer cell line and 300 µM for the normal MCF-10 cell line, indicating enhanced toxicity toward cancer cell lines. These findings suggested that poly(ARTEMA) induces ferroptosis in cancer cells and may serve as a promising candidate for cancer therapy with minimal cytotoxicity. To the best of our knowledge, this report may be the first that successfully synthesized poly(ARTEMA) using ART, with its anticancer potential evaluation.
Journal Article
A Smart Hyperthermia Nanofiber-Platform-Enabled Sustained Release of Doxorubicin and 17AAG for Synergistic Cancer Therapy
This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery.
Journal Article
A facile approach to preparing personalized cancer vaccines using iron-based metal organic framework
Considering the diversity of tumors, it is of great significance to develop a simple, effective, and low-cost method to prepare personalized cancer vaccines.
In this study, a facile one-pot synthetic route was developed to prepare cancer vaccines using model antigen or autologous tumor antigens based on the coordination interaction between Fe
ions and endogenous fumarate ligands.
Herein, Fe-based metal organic framework can effectively encapsulate tumor antigens with high loading efficiency more than 80%, and act as both delivery system and adjuvants for tumor antigens. By adjusting the synthesis parameters, the obtained cancer vaccines are easily tailored from microscale rod-like morphology with lengths of about 0.8 μm (OVA-ML) to nanoscale morphology with sizes of about 50~80 nm (OVA-MS). When cocultured with antigen-presenting cells, nanoscale cancer vaccines more effectively enhance antigen uptake and Th1 cytokine secretion than microscale ones. Nanoscale cancer vaccines (OVA-MS, dLLC-MS) more effectively enhance lymph node targeting and cross-presentation of tumor antigens, mount antitumor immunity, and inhibit the growth of established tumor in tumor-bearing mice, compared with microscale cancer vaccines (OVA-ML, dLLC-ML) and free tumor antigens.
Our work paves the ways for a facile, rapid, and low-cost preparation approach for personalized cancer vaccines.
Journal Article
Fluidic substrate as a tool to probe breast cancer cell adaptive behavior in response to fluidity level
Although the roles of elastic components in breast cancer progression have been widely studied, the importance of matrix dissipative elements in regulating breast cancer behavior is still poorly understood. In this study, we designed viscosity-tunable fluidic substrates to investigate the effects of matrix viscosity on the alteration of breast cancer cellular fate using a hydrophobic molten polymer of poly(ε-caprolactone-co-D,L-lactide) [P(CL-co-DLLA)] with different levels of fluidity. The high- and low-fluidity substrates used in this study were shown to behave as viscoelastic liquids at physiological temperature. A nonmetastatic breast cancer cell line (MCF-7) was cultured at the interface of the fibronectin-coated substrate, and its behavior towards the substrate fluidity level was thoroughly characterized. Despite fibronectin-mediated cell-substrate interactions, MCF-7 cells show sensitivity to substrate fluidity levels by forming types aggregates of different sizes and structures over time. Accordingly, MCF-7 cells were undergoing senescence on fluidic substrates, as shown by high metabolic activity over time, suppressed proliferation ability, and positive expression of senescence markers. Moreover, senescence implies more resistance towards anticancer drug treatment. This indicates that a fluidic substrate, as a two-dimensional synthetic matrix system, could demonstrate the importance of mechanical cues in redefining cellular function and cellular fate by changing the viscosity of the pure substrate.A fluidic substrate behaving as a hydrophobic viscoelastic liquid was designed as a tool to investigate the role of matrix viscosity on the alteration of breast cancer cellular fate. The fluidity level of fluidic substrate was tuned by modulating the molecular weight of poly(ε-caprolactone-co-D,L-lactide). MCF-7 cells responded to the change in fluidity level of fluidic substrates by forming weak attachment. On high-fluidity substrate, MCF-7 cells formed 3D aggregates, while coalesced on low-fluidity substrate. More importantly, the fluidic substrate mechanically promoted senescence of MCF-7 cells regardless the fluidity level of substrate.
Journal Article