Recent advances for liquid metals:Synthesis,modification and bio-applications

Considering the application requirements for modern biomedicine,research into novel biomaterials with unusual functions is highly desired.As an alternative,liquid metals(LMs),a nontraditional family of metal materials,have piqued the interest of biomedical researchers and made significant advances in biomed-ical areas,owing to their shape transformability,self-healing capability,excellent electrical,and thermal conductivities.In particular,many functionalized strategies for the preparation and modification of LMs or LMs-based composites to achieve extended biomedical applications have been investigated in recent years.These findings provided inspiring while constructive reference for the fabrication and engineering of novel LMs-based composites.Herein,in this topic review,we elaborate on the recent advances of LMs-based functional materials,with particular focuses on the synthesis,modification,and bio-applications,especially in antitumor therapy,antibacterial,contrast agent for imaging,bone repair,electronic skin sen-sor,and nerve connection agent.Further on,the current challenges and future prospects of LMs-based composites are carefully discussed.

Effect of nanoheat stimulation mediated by magnetic nanocomposite hydrogel on the osteogenic differentiation of mesenchymal stem cells

Hyperthermia has been considered as a promising healing treatment in bone regeneration. We designed a tissue engineering hydrogel based on magnetic nanoparticles to explore the characteristics of hyperthermia for osteogenic regeneration. This nanocomposite hydrogel was successfully fabricated by incorporating magnetic Fe_3O_4 nanoparticles into chitosan/polyethylene glycol(PEG) hydrogel, which showed excellent biocompatibility and were able to easily achieve increasing temperatures under an alternative magnetic field(AMF). With uniformly dispersed nanoparticles, the composite hydrogel resulted in high viability of mesenchymal stem cells(MSCs), and the elevated temperature contributed to the highest osteogenic differentiation ability compared with direct heat treatment applied under equal temperatures. Therefore, the nanoheat stimulation method using the magnetic nanocomposite hydrogel under an AMF may be considered as an alternative candidate in bone tissue engineering regenerative applications.

Doxorubicin-Ioaded Fe3O4@MoS2-PEG-2DG nanocubes as a theranostic platform for magnetic resonance imaging- guided chemo-photothermal therapy of breast cancer

Molybdenum disulfide （MoS2）, a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging （MRI）-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe3O4@MoS2 nanocubes （IOMS NCs） via the integration of MoS2 （MS） film onto iron oxide （IO） nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose （2-DG）, a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG- modified PEGylated NCs （IOMS-PEG-2DG NCs） acted as drug-carriers for doxorubicin （DOX）, which could be easily loaded within the NCs. The obtained IOMS-PEG（DOX）-2DG NCs exhibited a 3？2 relaxivity coefficient of 48.86 （mM）^-1·s^-1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG（DOX）-2DG NCs, the tumor site was clearly detected by enhanced T2-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 rain at a low power density of 0.5 W·cm^-2 a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.

General synthesis of high-performing magneto-conjugated polymer core-shell nanoparticles for multifunctional theranostics

Recently, increasing attention has been paid to magneto-conjugated polymer core-shell nanoparticles （NPs） as theranostic platforms. However, the utilization of surfactants and extra oxidizing agents with potential toxicity in synthesis, the lack of general methods for the controlled synthesis of various kinds of magnetic NP （MNP）@conjugated polymer NPs, and the difficulty of obtaining balanced magneto-optical properties have greatly limited the applications of magneto-conjugated polymers in theranostics. We developed an in situ surface polymerization method free of extra surfactants and oxidizing agents to synthesize MNP@polypyrrole （PPy） NPs with balanced, prominent magneto-optical properties. MNP@PPy NPs with an adjustable size, different shapes, and a controlled shell thickness were obtained using this method. The method was extended to synthesize other MNP-conjugated polymer core-shell NPs, such as MNP@polyaniline and MNP@poly（3,4-ethylenedioxythiophene）：poly（4- styrenesulfonate） （PEDOT：PSS）. We discuss the formation mechanism of the proposed method according to our experimental results. Finally, using the optical and magnetic properties of the obtained MNP@PEDOT：PSS NPs, in vivo multimodal imaging-guided hyperthermia was induced in mice, achieving an excellent tumor-ablation therapeutic effect. Our work is beneficial for extending the application of MNP-conjugated polymer core-shell NPs in the biomedical field.

Necroptosis-elicited host immunity:GOx-loaded MoS_(2) nanocatalysts for self-amplified chemodynamic immunotherapy

Nanoparticles induced potent antitumor immunotherapy plays a significant role for enhancing conventional therapeutic effectiveness.However,revealing the pathway of how nanoagents themselves trigger the host immunity or how to maximize the immunotherapy efficacy still needs further exploration.Herein,rose-like MoS2 nanoflowers modified with 2-deoxy-D-glucose(2-DG)and glucose oxidase(GOx)(MPGGFs)have been successfully fabricated via a one-pot hydrothermal reaction and following one-by-one surface modification as a multifunctional nanocatalyst for photothermal therapy enhanced self-amplified chemodynamic immunotherapy(PTT-co-CDT).By introducing GOx,the obtained MPGGFs exhibited self-amplified chemodynamic therapeutic efficacy under hypoxia tumor microenvironment(TME)because of the raised intracellular H2O2 level via enzyme-catalysis of oxygen.Furthermore,combined with the intrinsic excellent photothermal conversion efficiency of MoS2 nanoflowers,PTT-co-CDT performances by MPGGFs could effectively induce the necroptosis of tumor cells both in vitro and in vivo.Then the induced necroptosis via PTT-co-CDT by MPGGFs could directly trigger host immunity by activating the antigen-specific T-cells(CD4^(+) and CD8^(+)).Finally,the excellent in vivo safety of MPGGFs makes us believe that the successful construction of rose-like multifunctional nanocatalyst not only has great potentials for self-amplified chemodynamic immunotherapy,but also provides a paradigm for exploring necroptosis triggered host immunity for cancer treatment.

Synthesis of hierarchical sieve-like mesoporous silica nanoparticle aggregates via centrifugal method for drug delivery system

A facile approach towards the synthesis of a novel hierarchical sieve-like structure of mesoporous silica nanoparticle aggregates(hsMSNA) is reported using a centrifugal method at room temperature, based on the Kelvin-Helmholtz instability and soft-template method. The developed approach is simple and can potentially be applied for scaled-up preparation. Importantly, scanning electron microscopy,transmission electron microscopy, small-angle X-ray diffraction, and nitrogen adsorption-desorption experiments characterize the mesoporous silica as hsMSNA consisting of 40-100 nm mesoporous silica nanoparticles piled at 1-2 μm cylindrical pores in sieve-like tissues. Further, various pore sizes and sievemesh-, and vesicular-like structures can be obtained by adjusting the reaction conditions. The BrunauerEmmett-Teller specific surface area is as large as 500 m~2/g with a 47 cm~3/g pore volume, facilitating easy drug loading and delivery. Cytotoxicity assays show that the samples are not cytotoxic under a high concentration of 200μg/mL. Finally, the high drug encapsulation efficiency and sustained release behaviors indicats the considerable potential of the hsMSNA as a drug delivery system in the field of nanomedicine.

Galvanic replacement reaction for in situ fabrication of litchi-shaped heterogeneous liquid metal-Au nano-composite for radio-photothermal cancer therapy

With tremendous research advances in biomedical application,liquid metals(LM)also offer fantastic chemistry for synthesis of novel nano-composites.Herein,as a pioneering trial,litchi-shaped heterogeneous eutectic gallium indium-Au nanoparticles(EGaIn-Au NPs),served as effective radiosensitizer and photothermal agent for radio-photothermal cancer therapy,have been successfully prepared using in situ interfacial galvanic replacement reaction.The enhanced photothermal conversion efficiency and boosted radio-sensitization effect could be achieved with the reduction of Au nanodots onto the eutectic gallium indium(EGaIn)NPs surface.Most importantly,the growth of tumor could be effectively inhibited under the combined radio-photothermal therapy mediated by EGaIn-Au NPs.Inspired by this approach,in situ interfacial galvanic replacement reaction may open a novel strategy to fabricate LM-based nano-composite with advanced multi-functionalities.