Mechanical cancer therapy utilizing ultrasound and magnetic fields is regarded as an emerging effective therapeutic strategy. This review highlights the latest advances in applications of mechanical cancer therapy to present novel perspectives.

Natural extracellular matrix (ECM) can regulate the interactions between cells and ligands by exhibiting heterogeneous nano-sequences periodically displaying adhesive ligands, such as RGD ligand in vivo. [1,2] Cell-adhesive ECM proteins, such as fibronectin, vitronectin, and collagen, were shown to form periodically sequenced RGD ligand-bearing nanostructures (67-100 nm). [1] Periodic structure in reflectance was also observed from native tissues. [2] The ligation of integrin with adhesive ligand mediates the assembly of cytoskeletal actin filaments and focal adhesion (FA) complexes to activate mechanosensing signaling pathways that can regulate cellular differentiation. [3,4] Strategically developing materials with heterogeneously sequenced ligand nanostructures can emulate ECM [5] microenvironment to help elucidate the interactions between cells and nano-ligands with tunable frequency and sequences. This can effectively regulate diverse cellular adhesion and functionality in vivo, such as FA, mechanosensing, and differentiation of stem cells. [6] The native extracellular matrix (ECM) can exhibit heterogeneous nanosequences periodically displaying ligands to regulate complex cell-material interactions in vivo. Herein, an ECM-emulating heterogeneous barcoding system, including ligand-bearing Au and ligand-free Fe nano-segments, is developed to independently present tunable frequency and sequences in nano-segments of cell-adhesive RGD ligand. Specifically, similar exposed surface areas of total Fe and Au nano-segments are designed. Fe segments are used for substrate coupling of nanobarcodes and as ligand-free nanosegments and Au segments for ligand coating while maintaining both nanoscale (local) and macroscale (total) ligand density constant in all groups. Low nano-ligand frequency in the same sequences and terminally sequenced nano-ligands at the same frequency independently facilitate focal adhesion and mechanosensing of stem cells, which are collectively effective both in vitro and in vivo, thereby inducing stem cell differentiation. The Fe/RGD-Au nanobarcode implants exhibit high stability and no local and systemic toxicity in various tissues and organs in vivo. This work sheds novel insight into designing biomaterials with heterogeneous nano-ligand sequences at terminal sides and/or low frequency to facilitate cellular adhesion. Tuning the electrodeposition conditions can allow synthesis of unlimited combinations of ligand nano-sequences and frequencies, magnetic elements, and bioactive ligands to remotely regulate numerous host cells in vivo.

This review highlights recent advances in the utilization of various endogenous and exogenous stimuli to activate nanocarrier-based ferroptosis cancer therapy that can be effective in treating conventional drug-resistant tumors.

This review summarizes a novel perspective on emerging 1-D nanomaterials for cancer therapy and diagnosis, highlighting the unique shape-dependent properties, recent advancements, and unexplored nanomaterial types and therapeutic applications.

In native microenvironment, diverse physical barriers exist to dynamically modulate stem cell recruitment and differentiation for tissue repair. In this study, nanoassembly‐based magnetic screens of various sizes are utilized, and they are elastically tethered over an RGD ligand (cell‐adhesive motif)‐presenting material surface to generate various nanogaps between the screens and the RGDs without modulating the RGD density. Large screens exhibiting low RGD distribution stimulate integrin clustering to facilitate focal adhesion, mechanotransduction, and differentiation of stem cells, which are not observed with small screens. Magnetic downward pulling of the large screens decreases the nanogaps, which dynamically suppress the focal adhesion, mechanotransduction, and differentiation of stem cells. Conversely, magnetic upward pulling of the small screens increases the nanogaps, which dynamically activates focal adhesion, mechanotransduction, and differentiation of stem cells. This regulation mechanism is also shown to be effective in the microenvironment in vivo. Further diversifying the geometries of the physical screens can further enable diverse modalities of multifaceted and safe unscreening of the distributed RGDs to unravel and modulate stem cell differentiation for tissue repair.