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Page 10 of 26 Yang et al. Soft Sci 2024;4:9 https://dx.doi.org/10.20517/ss.2023.43

underlying mechanism of the PT effect of LMNPs has not been revealed explicitly. Nonetheless, this effect
has still been widely studied and extended to realize diverse functionalities. Sun et al. prepared variform
[40]
LMNPs and characterized their morphology-dependent PT conversion efficiency . The stability of PT
agents is always of great concern, especially considering the fact that temperature rise causes oxidization and
morphing of LMNPs, as discussed earlier in this paper, which would cause exacerbation of the efficiency.
Wrapped with non-PT coatings, LMNPs were able to resist shape morphing and realize stable repeated self-
heating. Hu et al. manifested that LMNPs coated with mesoporous silica displayed enhanced
[79]
immobilization and sustained PT effect . Besides direct hyperthermic damage to cancer cells, the PT effect
could also cooperate with chemotherapy or embolization to realize synergistic treatment [Figure 3D].
Grafted with functional ligands, LMNPs could carry anti-tumor drugs and release them when triggered by
self-heating under irradiation, which further improves the tumor elimination efficiency [47,79,80] . Wang et al.
integrated PT treatment, chemotherapy, and embolization in one combinational material . They
[57]
successfully encapsulated EGaIn-Fe nanoparticles and doxorubicin hydrochloride into alginate hydrogels.
This hybrid agent could be immobilized at the main artery of the tumor, perform the PT effect under
irradiation, and thus trigger drug release to the targeted tumor tissues.

Inductive heating
In recent years, magnetic inductive heating has been studied in tumor therapy and vitrified
cryopreservation. Compared to PT techniques, the actuation range is restricted by irradiation area, and
magnetic inductive heating holds two major superiorities: (i) a larger actuation scale and (ii) better
flexibility of manipulation. Fe O is the most applied magnetic agent for inductive heating. Manuchehrabadi
3
4
et al. applied Fe O nanoparticles and manifested the capability of magneto-inductive heating to rapidly and
3
4
uniformly thaw vitrified arteries up to 50 mL . Zhan et al. applied this technique with carboxylic acid-
[24]
modified Fe O to resuscitate cryopreserved whole rat kidneys and achieve integral structures . Han et al.
[76]
3
4
applied this strategy to vitrify rat kidneys for 100 days and rewarmed them with a nanowarming strategy.
They transplanted post-thawed kidneys into receptor rats and found that the renal functions recovered back
to normal levels after 2-3 weeks after early dysfunction . As metallic materials, LMs are also appropriate
[81]
for this technique. Under an alternating magnetic field, an eddy current will be produced due to Faraday’s
law of induction, thus generating heat inside the metal. Wang et al. demonstrated a more considerable heat
[82]
generation of LM than Fe O in an alternating magnetic field [Figure 3C]. Then, by modifying LMs with
4
3
polyethylene glycol (PEG) and doxorubicin (DOX), they realized thermo-chemo hybrid therapy. In
another work, Wang et al. prepared oxidized EGaIn to conformally coat the skin of mice and generate
considerable heat under an alternating magnetic field to actualize thermal therapy for subcutaneous
tumors . With such a highly efficient inductive heating effect, LMs hold great potential in vitreous
[72]
cryopreservation.
BIOSAFETY
In biological applications, the safety of materials always stands as the top priority. Unlike mercury, which
easily vaporizes in the atmosphere and causes inhalation risk, Ga-based room-temperature LMs have
extremely low saturated vapor pressure, thereby eliminating the need for special packaging for long-term
storage. Despite the natural stability, the toxicity of LMs in biological environments still attracts great
attention. Both in vitro and in vivo toxicity of LMs, whether in bulk formation or particles, will be discussed
in this section.

Ex vivo cytotoxicity
For Ga-based LMs, the major factor that causes cellular toxicity is ionic release. Kim et al. systematically
evaluated the ionic toxicity of EGaIn in the aqueous environment . For bulk EGaIn, Ga concentration
3+
[83]
increased with soaking time until saturated, while In stayed at a negligible level. The cytotoxicity was
3+