Aug 7 2023Reviewed by Skyla Baily
Liquid metals (LM) like pure gallium (Ga) and Ga-based alloys are considered to be a new class of materials exhibiting special physicochemical properties.
A versatile liquid metal (LM) gallium-indium alloy has been used to develop a novel LM nanoparticle that harbors an immunomodulant and an immune checkpoint inhibitor, Anti-PD-L1. Upon irradiation by near infra-red light, Anti-PD-L1 specifically binds to the cancer cell, while immunostimulants activate T and dendritic cells. This synergistic activation coupled with the photothermal effect effectively eliminates the cancer cell almost immediately. Image Credit: Eijiro Miyako from Japan Advanced Institute of Science and Technology
One of the most notable applications of LMs is photothermal therapy against cancer, in which functional LM nanoparticles transform light energy to heat energy, thus killing cancerous cells. LM-based phototherapy is better than traditional cancer therapy due to its high repeatability, specificity, and few side effects.
In a new cutting-edge study, Associate Professor Eijiro Miyako and his collaborators from Japan Advanced Institute of Science and Technology (JAIST) synthesized multifunctional Ga-based nanoparticles that integrate cancer phototherapy with immunotherapy.
The synthesized novel LM nanoparticle (PEG-IMIQ-LM) consists of an immunological modulator imiquimod (IMIQ), and eutectic gallium-indium (EGaIn) LM alloy, and both fitted within a biocompatible surfactant DSPE-PEG2000-NH2. The study findings were reported in the journal Advanced Functional Materials.
We believe that the convergence of nano-immuno engineering and LM technology could provide a promising modality to trigger ideal immune responses for advancing cancer immunotherapy. In this study, we report light-activatable multifunctional LM nanoparticles with immunostimulants to combine photothermal therapy with immunotherapy.
Dr. Miyako, Associate Professor, Japan Advanced Institute of Science and Technology
Advanced Materials eBook Compilation of the top interviews, articles, and news in the last year. Download a free copy Initially, the research group made water-dispersible LM nanoparticles via a simple one-step sonication process with the help of DSPE-PEG2000-NH2 to initiate IMIQ. This is known to be a huge discovery, as EGaIn LM is naturally a water-immiscible material.
Additional investigations verified that LM disintegrates to guarantee IMIQ delivery to the target. Furthermore, the prepared nanoparticle exhibited a linear increase in absorbance in the near-infrared (NIR) region at 808 nm, thereby verifying its optically activatable nature.
When the aqueous solution of the LM nanoparticle was irradiated by the NIR laser (808 nm), the team noted a remarkable increase in the temperature of the solution, which was proportional to the rise in the nanoparticle concentration.
These study outcomes verified that PEG-IMIQ-LM nanoparticle was a strong and stable photothermal drug carrier, which is ideal for immunotherapy.
Additional experiments disclosed that LM nanoparticles were extremely safe and did not lead to cytotoxicity in mouse colon cancer (Colon26) and human fibroblast (MRC5) cells.
To evaluate the degree of internalization and distribution of the particles, a fluorescent dye called indocyanine green (ICG) was initiated into the particle via sonication leading to PEG–ICG–IMIQ–LM particle.
Fluorescent (FL) microscopy fitted with a laser beam illustrated that the LM particle exhibited strong fluorescence at several NIR wavelengths and instantly ruined the Colon26 cells.
Hence, LM particles could not just efficiently provide the immunomodulant, but could also allow their real-time tracking and removal of particular cancer cells.
Eventually, the team came up with a multifaceted LM immune nano stimulator for cancer theranostics. For this to be done, they added anti-programmed death ligand-1 antibody (Anti-PD-L1), one of the most hopeful immune checkpoint inhibitors, to the present fluorescent LM nanoparticle.
The modified particle, Anti-PD-L1‒PEG–ICG–IMIQ–LM, was dispersed efficiently with considerable fluorescence. With rising time post-irradiation, the tumor surface temperature went up linearly, indicative of the antitumor effect of the nanoparticle.
The addition of Anti-PD-L1 onto the nanoparticle allowed the binding of the LM particle to PD-L1 on the cancer cells, thereby marking them for phagocytosis by dendritic cells (DC) and macrophages. Laser-induced Anti-PD-L1–PEG–IMIQ–LM particles displayed the highest and full cancer removal, together with quicker healing and recovery.
Furthermore, when the tumor recurred, mice treated with laser-induced Anti-PD-L1–PEG–IMIQ–LM particles exhibited prolonged survival and sustained antitumor effectiveness.
We believe that these synergistic immunological effects and optical nanofunctions of LMs have wide therapeutic applications and might contribute to innovative cancer theranostic technologies. We are hopeful that this technology will be available for clinical trials in 10 years.
Dr. Miyako, Associate Professor, Japan Advanced Institute of Science and Technology
Journal Reference
Qi, Y., et al. (2023) Light-Activatable Liquid Metal Immunostimulants for Cancer Nanotheranostics. Advanced Functional Materials. doi.org/10.1002/adfm.202305886.
Source: http://www.jaist.ac.jp/english/
