We described a magnetic chitosan microscaffold tailored for applications requiring high biocompatibility, biodegradability, and monitoring by real-time imaging. Such magnetic microscaffolds exhibit adjustable pores and sizes depending on the target application and provide various functions such as magnetic actuation and enhanced cell adhesion using biomaterial-based magnetic particles. Subsequently, we fabricated the magnetic chitosan microscaffolds with optimized shape and pore properties to specific target diseases. As a versatile tool, the capability of the developed microscaffold was demonstrated through in vitro laboratory tasks and in vivo therapeutic applications for liver cancer therapy and knee cartilage regeneration. We anticipate that the optimal design and fabrication of the presented microscaffold will advance the technology of biopolymer-based microscaffolds and micro/nanorobots.

Exosomes are nanosized extracellular vesicles secreted by various cell types, including those of the immune system, such as natural killer (NK) cells. They play a role in intercellular communication by transporting signal molecules between the cells. Recent studies have reported that NK cell-derived exosomes (NK-exo) contain cytotoxic proteins-induced cell death. However, the characteristics and potential functions of NK-exo, especially for the liver cancer are poorly understood. In this study, we investigated the anti-tumor effects of NK-exo in the primary liver cancer, hepatocellular carcinoma (HCC), using the orthotopic and subcutaneous tumor model. We found that NK-exo expressed both typical exosomal markers (e.g. CD63, CD81, and Alix) and cytotoxic proteins (e.g. perforin, granzyme B, FasL, and TRAIL). NK-exo were selectively taken up by HCC cells (e.g. Hep3B, HepG2, and Huh 7). Interestingly, Hep3B cells induced the highest cytotoxicity compared with HepG2 and Huh7 cells, and substantially enhanced the apoptosis by NK-exo. Furthermore, we demonstrated that NK-exo inhibited the phosphorylation of serine/threonine protein kinases (e.g. AKT and ERK1/2), and enhanced the activation of specific apoptosis markers (e.g. caspase-3, -7, -8, -9, and PARP) in Hep3B cells. NK-exo also exhibit the active targeting ability and potent therapeutic effects in both orthotopic and subcutaneous HCC mouse models. Overall, these results suggest that NK-exo indicate strong anti-tumor effects in HCC, which are mediated by novel regulatory mechanisms involved in serine/threonine kinase pathway-associated cell proliferation and caspase activation pathway-associated apoptosis.

This paper describes the design of poly(benzyl ether)-based amphiphiles that are capable of selective and molecular demicellization via headto-tail depolymerization, triggered by a specific stimulus. The amphiphiles were synthesized by living anionic polymerization with sequential additions of two quinone methide monomers, followed by postpolymerization reaction. The amphiphiles also effectively formed polymeric micelles under aqueous conditions. The cooperative depolymerization behavior and assembly propensity of the copolymers enabled depolymerization-induced demicellization, which proceeded completely or partially under the control of an applied molecular signal. As a proof of concept, a hydrophobic model drug, doxorubicin, was loaded inside the micelles, which were then degraded on the molecular level, leading to controlled yet complete release of the cargo molecules. It is envisioned that the design concept for the micelles can be further expanded to targeted delivery systems or removable micellar encapsulants.

In this paper, a hierarchical design of supramolecular hydrogels comprising two individual supramolecular networks that are capable of exhibiting reversible and programmed behaviors is described. Both component networks are established by (i) conformational transformation of natural polysaccharides and (ii) host–guest interaction between separate polymer chains. Sequential formation of each orthogonal network generates an interpenetrated structure, which results in the formation of biobased, completely noncovalent, double-network hydrogels. Owing to the intrinsic advantages of the cross-linking system, the hydrogel materials demonstrated the reversibility of physical properties in response to heat or light and exhibited macroscopic performance such as self-healing or injectable properties without calamitous structural collapse. In particular, it was possible to demonstrate the superstructured hydrogels as a responsive vector. Selected dye or drug molecules were loaded during the formation of the networks, and sustained release behavior was achieved around body temperature, which could be fairly enhanced upon UV-light irradiation. Also, we were able to develop a three-dimensional, bioprinted, large-scale pattern using the hydrogels as a bioink. We envisage that the designed hydrogels can be further advanced by employing other cargo molecules or supramolecular chemistries, which would create emerging, autonomous materials suitable for bioengineered scaffolds or coating layers that are implantable and highly sensitive to physiological signals.

Various cell therapy strategies, including chimeric antigen receptor-expressing T or natural killer (NK) cells and cell-mediated drug delivery, have been developed for tumor eradication. However, the efficiency of these strategies against solid tumors remains unclear. We hypothesized that real-time control and visualization of therapeutic cells, such as NK cells, would improve their therapeutic efficacy against solid tumors. In this study, we engineered Sonazoid microbubble-conjugated NK (NK_Sona) cells and demonstrated that they were detectable by ultrasound imaging in real-time and maintained their functions. The Sonazoid microbubbles on the cell membrane did not affect the cytotoxicity and viability of the NK cells in vitro. Additionally, the NK_Sona cells could be visualized by ultrasound imaging and inhibited tumor growth in vivo. Taken together, our findings demonstrate the feasibility of this new approach in the use of therapeutic cells, such as NK cells, against solid tumors.