Advanced Functional Materials: New applications of iron death: Chinese scholars develop cancer diagnosis and collaborative therapy based on iron death

As one of the most abundant elements on Earth, iron is the main functional element
in hemoglobin and many different enzymes that sustain life.
The right amount of iron ions in the human body is good
for health.
Notably, the accumulation of iron ions in cells may lead to cell death, a programmed cell death induced by iron-dependent reactive oxygen species (ROS) production, defined as ferroptosis in 2012
.

Recently, in order to develop new cancer therapies, the treatment of iron death in cancer cells has attracted more and more attention and gradually developed into the main mode
of chemokinetic therapy (CDT).
Therefore, various iron-based nanomaterials have been developed for the treatment and diagnosis of cancer, not only because of the iron dyosis effect, better biocompatibility and low cost advantages, but also because of the excellent physicochemical properties of iron-based nanomaterials, such as superparamagnetic properties
.
Another advantage of magnetic, iron-based nanotherapeutics is that precise diagnosis
of tumors is achieved simultaneously through magnetic resonance imaging (MRI).

Due to its high tissue penetration and spatial resolution, magnetic resonance imaging (MRI) is one of
the most widely used imaging diagnostic methods.
However, the existing magnetic iron-based MRI contrast agents mainly achieve a single imaging effect of lateral relaxation (T2-weighted MRI), which is difficult to achieve significant imaging diagnosis
for low-resolution tissues and tumor sites.
Therefore, the development of intelligent magnetic iron-based MRI contrast agents that improve diagnostic results is of great significance
for the accurate diagnosis of tumors.
Recently, dynamically switchable MRI contrast agents, which can activate switchable MR imaging from T2 to T1 or T1 to T2 through specific TMEs, are becoming research hotspots
for high-resolution MRI.

Recently, the Qin Yan research group of the Institute of Biophysics of the Chinese Academy of Sciences cooperated with Professor Jianzhuang Jianzhuang and Professor Wang Tianyu of the University of Science and Technology Beijing to publish a title in the journal Advanced Functional Materials Research paper on Modulated ultrasmall γ-Fe2O3 nanocrystal assembles for switchable magnetic resonance imaging and photothermal-ferroptotic-chemical synergistic cancer therapy.

The study carried out ambulatory MRI diagnosis of cancer and synergistic therapy of iron death treatment, photothermal therapy (PTT) and chemotherapy
.

The research team developed a multi-grade Fe2O3 structure by modulating the ultra-small γ-Fe2O3 nanocrystal assembly, and further combined with the targeted molecular folic acid (FA) and chemotherapy drugs (Dox) to obtain the multifunctional tumor diagnosis and treatment nanodrug UNA-γ-Fe2O3@PAH/PAA@Dox@PEG-FA (UF@PPDF NPs).

The hierarchical assembly structure of UF@PPDF NPs greatly improves the utilization efficiency of iron and achieves extremely high photothermal conversion efficiency
in the second near-infrared region (NIR-II).
For MRI, the UF@PPDF can clearly display the size and density of the tissue through dynamic T2-T1 imaging switching, and achieve high-resolution diagnosis
of tumors.

At the same time, UF@PPDFNPs showed a highly effective PTT effect under NIR-II irradiation, as well as the controlled release of iron ions and Dox, thereby realizing a three-function synergistic tumor treatment combining ferrozotic treatment
, photothermal therapy (PTT) and chemotherapy.
RNA sequencing (RNA-Seq) analysis of differentially expressed genes also revealed the multifaceted role
of this therapy in cancer cell signaling.
Cell respiration and electron transport are significantly upregulated, while epigenetic pathways, including chromatin modification and transcriptional activity, are severely downregulated, leading to apoptosis
.
Therefore, UF@PPDF NPs provide new possibilities
for efficient diagnosis and treatment of deep tumors.

UF@PPDF Synergistic tumor treatment
combining synthesis, dynamic switchable MRI diagnosis and ferrozotic-PTT-chemotherapy.

Prof.
Yan Qin and Prof.
Jianjun Luo from the Institute of Biophysics, Chinese Academy of Sciences, and Prof.
Jiang Jianzhuang and Prof.
Tianyu Wang from the University of Science and Technology Beijing are co-corresponding authors
of this paper.
Yang Baoshan, a doctoral candidate at University of Science and Technology Beijing, is the first author
of this paper.
Mao Wei, a researcher and graduate student at the Institute of Biophysics, Xue Rong provided assistance for MRI testing; Jianjun Luo, a researcher at the Institute of Biophysics, and Yiming Zhang, a graduate student, provided assistance
for RNA sequencing analysis.
Zhao Zunling, a doctoral student at the Institute of Biophysics, also participated in the research
.
The research was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China
.
The Laboratory Animal Platform of the Institute of Biophysics provided important technical support
for this research.

Original source:

Baochan Yang， Yiming Zhang， Lixin Sun， et al.
Modulated Ultrasmall γ-Fe2O3 Nanocrystal Assemblies for Switchable Magnetic Resonance Imaging and Photothermal-Ferroptotic-Chemical Synergistic Cancer Therapy.
Advanced Functional Materials， 2022.