To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core–shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity.
This work discusses the attributes, fabrication methods, and applications of gallium‐based liquid metal particles. Gallium‐based liquid metals combine metallic and fluidic properties at room temperature. Unlike mercury, which is toxic and has a finite vapor pressure, gallium possesses low toxicity and effectively zero vapor pressure at room temperature, which makes it amenable to many applications. A variety of fabrication methods produce liquid metal particles with variable sizes, ranging from nm to mm (which is the upper limit set by the capillary length). The liquid nature of gallium enables fabrication methods—such as microfluidics and sonication—that are not possible with solid materials. Gallium‐based liquid metal particles possess several notable attributes, including a metal–metal oxide (liquid–solid) core–shell structure as well as the ability to self‐heal, merge, and change shape. They also have unusual phase behavior that depends on the size of the particles. The particles have no known commercial applications, but they show promise for drug delivery, soft electronics, microfluidics, catalysis, batteries, energy harvesting, and composites. Existing challenges and future opportunities are discussed herein.
Soft conductors are created by embedding liquid metal nanoparticles between two elastomeric sheets. Initially, the particles form an electrically insulating composite. Soft circuit boards can be handwritten by a stylus, which sinters the particles into conductive traces by applying localized mechanical pressure to the elastomeric sheets. Antennas with tunable frequencies are formed by sintering nanoparticles in microchannels.
This paper reports the formation of shape-changing and phase-transforming liquid metal particles that have potential applications in drug delivery, catalysis, colloidal jamming, and optics.
Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of the endosomal escape strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by the systemic toxicity and lack of specificity. We describe here a light-fueled liquid-metal transformer for effective endosomal escape-facilitated cargo delivery via a chemical-mechanical process. The nanoscale transformer can be prepared by a simple approach of sonicating a low-toxicity liquid-metal. When coated with graphene quantum dots (GQDs), the resulting nanospheres demonstrate the ability to absorb and convert photoenergy to drive the simultaneous phase separation and morphological transformation of the inner liquid-metal core. The morphological transformation from nanospheres to hollow nanorods with a remarkable change of aspect ratio can physically disrupt the endosomal membrane to promote endosomal escape of payloads. This metal-based nanotransformer equipped with GQDs provides a new strategy for facilitating effective endosomal escape to achieve spatiotemporally controlled drug delivery with enhanced efficacy.
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