【Scientific Research Dynamics】Important progress in the research of Zhao Yanbing/Yang Xiangliang's research group: the radiofrequency field of bivalent gold nanoclusters activates tumor cell pyrozosis...

On December 29, ACS Nano, a journal of the American Chemical Society, published online the research paper "Radiofrequency-Activated Pyroptosis of Bi-Valent Gold" by Professor Zhao Yanbing and Professor Yang Xiangliang, School of Life Science and Technology, Huazhong University of Science and Technology, National Engineering Research Center for Nanomedicine Nanocluster for Cancer Immunotherapy”
。

Cancer immunotherapy shows great potential
in killing tumor cells.
However, it is only effective
in a small proportion of patients with features of "immunogenic thermal tumors" (≈10-30%).
Cancer cell death patterns play an important role
in regulating the tumor immune microenvironment.
For example, as a programmed cell death mode related to adaptive immune response, pyroptosis provides great help
for improving cancer immunotherapy by inducing immunogenic cell death (ICD), improving the infiltration of cytotoxic T lymphocytes, and triggering systemic immune response.
Studies have shown that the GasderminE (GSDME) protein plays a key role
in the pyroptosis process of tumor cells.
Since the expression level of GSDME protein in most tumor cells is very low, this largely inhibits tumor cell pyroptosis, and only non-immunogenic apoptosis
occurs.
Although some DNA methyltransferase inhibitors (dicetabine, 5-azacytidine, etc.
) can effectively increase the content of GSDME in tumor cells, the lack of activation of G SDME protein still greatly limits the pyroptosis
of tumor cells.
It has been reported that it can effectively regulate caspase 3/GSDME-mediated pyroptosis of tumor cells by promoting the activation of caspase 3, thereby exerting inhibitory effects
on tumors.
However, how to achieve the specific transformation of tumor cells from apoptosis to pyroptosis through the Caspase 3 pathway and improve the effect of cancer immunotherapy is still a huge challenge
.

Radiofrequency ablation (RFA) is one of the most commonly used methods of hyperthermia in the clinic, and Caspase 3-mediated apoptosis is the main pathway
of tumor cell damage in the peripheral region of R FA (heat load < 50°C).
Recently, non-invasive RFA procedures (radio frequency radiation) based on radiofrequency-responsive nanoparticles (RF-NPs) have attracted a lot of attention
as a promising form of hyperthermia.
Compared with traditional RFA, it does not need to insert electrode needles, has deep RF tissue penetration, flexible procedures, can accurately kill tumor cells, can activate caspase3 and continuously activate the immune response
to a certain extent.
In this work, the authors prepared radiofrequency-responsive bivalent gold nanoclusters (BI GC@PNA) using a two-step reduction method of weak reducing agent and strong reducing agent, which was modified by temperature-sensitive polymer to improve its in vivo behavior (cell uptake and intratumor retention,
etc.
).
By adjusting the ratio of weak reducing agent and strong reducing agent to accurately adjust the Au(I)/Au(0) ratio in bi GC@PNA, the RF heating effect was precisely controlled, and its effect
on cell pyroptosis was studied under a non-invasive RF field.
Changes in GSDME and caspase 3 expression levels in tumor cells and tumor-bearing mice showed that biGC@PNA exhibited a definite radiofrequency heat-activated pyroptosis of tumor cells, as well as a strong radiofrequency-induced ICD effect and systemic immune response
.
The combination with αPD-1 showed that radiofrequency response biGC@PNA showed excellent αPD-1 immunotherapy enhancement in inhibiting tumor lung metastasis, distant tumors, and re-attacking tumor growth
.
BIGC@PNA as a nanoeffector that activates pyroptosis in tumor cells by radiofrequency is expected to be a new strategy to enhance cancer immunotherapy (Figure 1).

ACS Nano is the world's leading journal
in the field of nanoscience and materials.
Qingqing Zhang, a doctoral student at the School of Life Science and Technology, Huazhong University of Science and Technology, is the first author
of the paper.
The research was supported by the National Basic Research Program of China (2020YFA0710700, 2018YFA0208900) and the National Natural Science Foundation of China (82172758, 81773653 ) funding
.

Article link: https://pubs.
acs.
org/doi/full/10.
1021/acsnano.
2c09242

Figure 1 Radiofrequency-activated pyrosis of tumor cells in BI GC@PNA is used in cancer immunotherapy