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Yang et al. Soft Sci 2024;4:9 https://dx.doi.org/10.20517/ss.2023.43 Page 21 of 26

resistance is observed after gallium treatment. The antibacterial effect of gallium relies on the disturbance to
the normal physiological activity of bacteria, producing a great amount of ROS and further affecting
microbial DNA and protein synthesis [123,124] . Truong et al. systemically summarized the fundamental
3+
mechanisms of the antimicrobial capability of gallium nanoparticles and gallium Ga , which are as follows:
(1) membrane disruption caused by Ga -induced oxidative stress; (2) Iron deprivation caused by Ga -Fe
3+
3+
3+
3+
competitive binding; (3) Ga binds with bacterial DNA and further causes DNA fragmentation; (4) Ga
3+
binds with bacterial proteins and disrupts the bacterial metabolism . Compared with solid metal
[125]
antimicrobial agents, Ga-based LMs are easy to synthesize from bulk to multi-dimension particles, showing
remarkable convenience in matching bacteria. It is self-evident that gallium has already become one of the
most promising antibacterial agents, with the potential for more prosperous future applications.
The emerging LM-mediated cryo-biomedicine is an interdisciplinary field with the efforts and cooperation
of material science, cryogenic engineering, and biomedicine. It is necessary to realize that LM-mediated
cryo-biomedicine is still in its initial stage, presenting a landscape where challenges and opportunities
coexist. Further development still requires efforts in underlying mechanisms, material design and synthesis,
and multi-scale regulation. A few issues still ask for further explorations: (1) LM-mediated synergistic effect
is worth pursuing. The combination of LMs and cryo-biomedicine provides a new approach in the face of
challenges. Researchers should explore more potential applications of LMs and their composites; (2)
Explore the application of LMs at nanoscales. Recently, the LM nanoparticles have been attracting
increasing attention compared to their bulk counterpart due to their unique properties in heat and mass
transfer. Thus, a more comprehensive understanding of LM nanoparticles in cryo-biomedical systems
should be considered; (3) Achieving more precise regulation is desirable by improving LM preparation
programs and advanced modulating techniques; (4) The interface characteristics are of great significance for
LMs. Thus, tuning the proper interface between LMs and biological systems is essential for their
performance. Overall, the new rising direction holds broad prospects but also requires a joint effort from
interdisciplinary contribution. We do believe that LMs will accelerate the development of cryo-biomedicine,
and many breakthroughs will emerge with their promotion.

DECLARATIONS
Authors’ contributions
Proposed original conceptualization: Lu C, Yang F, Rao W
Outlined the manuscript structure: Lu C
Investigated literature and wrote the original manuscript: Lu C, Yang F
Designed original figures: Yang F
Reviewed and revised the manuscript: Lu C, Rao W
Supervised the manuscript: Rao W

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work is financially supported by the National Natural Science Foundation of China (No. 51890893).

Conflicts of interest
All authors declared that there are no conflicts of interest.