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Bai et al. Soft Sci 2023;3:40 https://dx.doi.org/10.20517/ss.2023.38 Page 7 of 34

[115]
LMNPs grafted with different molecules was up to 90% or even more than 100% [Figure 2A ii] .

At the tissue level, Sun et al. administered LMNPs intravenously to mice and performed H&E stained
images of several tissue sites, including heart, liver, spleen, lung, kidney, and brain; after photothermal
[116]
treatment and execution of the mice, no significant tissue damage was detected [Figure 2B] .

At the organ level, Lu et al. explored the effects of LMNPs on major liver function indicators, including
alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin
concentrations, and blood urea nitrogen (BUN), which remained largely unchanged after intravenous
[117]
administration, suggesting no substantial toxicity of LMNPs [Figure 2C] .
At the living organisms level, Chechetka et al. found that all five mice survived normally for 19 days after
[114]
being injected with LMNPs [Figure 2D i] . Lu et al. suggested that the mice may have cleared the injected
[117]
LMNPs through their feces and liver and excreted them [Figure 2D ii] . Meanwhile, Sun et al. conducted
in vivo experiments on different forms of LMNPs, among which gallium nanorods and gallium
nanospheres did not reveal any abnormalities in body weight and blood tests in mice in the experimental
concentration range [Figure 2D iii] ; however, for gallium-indium alloy nanorods (LMNR) containing
[116]
indium, mice showed weight loss on the third day, and abnormally high white blood cell data up to about
300% were found starting on the seventh day . This indicates that excess indium ions are enriched in
[116]
organisms for long periods of time and may pose a potential threat to the health of organisms. Further
illustrating LMNPs of other elements, indium NPs do not release indium ions under static conditions in
water while applying ultrasound stimulation rapidly increases indium ion concentration [106,118] , and excessive
concentrations of indium ions have now been shown to cause physical weakness, weight loss, liver and
spleen lesions, and more in humans .
[119]

In conclusion, gallium-based LMNPs have been widely used in biomedical research, such as drug delivery,
medical imaging, and cancer therapy [114,120,121] due to acceptable low toxicity. However, when LMNPs are
injected into organisms, especially in large quantities or accompanied by subsequent operations such as
ultrasound and laser, the metabolism of metal ions, such as gallium and indium ions, by the organisms
should be monitored in a timely manner and a comprehensive long-term biological health testing to ensure
the stability and safety of biomaterials.

PREPARATION OF NANO-LMS
As is commonly known, the current approaches can be divided into bottom-up and top-down ideas
[122]
according to the idea of preparing NPs . For LMs, bottom-up approaches mainly include physical vapor
[123]
[124]
deposition and thermal decomposition , which allow for the controlled size distribution of NPs.
However, the preparation processes are more complex compared to top-down approaches. Given the
excellent deformability of LMs, top-down preparation of NPs has become a more widely accepted method,
with ultrasonic preparation and mechanical shearing being the two dominant approaches for large-scale
fabrication, which will be introduced in the following.

Ultrasonication
Ultrasonication is widely used to prepare LM nanomaterials as a top-down strategy. The ultrasonic probe
vibrates to arouse microbubbles and cavities within the solvent, generating localized high temperature and
pressure, which strongly shatter the bulk LM into smaller droplets [112,125] [Figure 3A]. The eventual mean size
and morphology of LMNPs are influenced by various factors such as the frequency and duration of the
applied ultrasound [125,126] , the type of solvent used for the sonication , and the temperature during
[125]