Peking University Graduate School of Medical Technology makes series of advances in the direction of tumor therapy research via extracellula

Posted on November 29, 2022 Reads:

Cancer is a major disease that seriously threatens human life and social development, and is currently the first or second leading cause of death for the population in 112 countries, according to the World Health Organization (WHO) in 2019. In recent decades, with the shift in disease patterns and the trend of population aging, the burden of cancer in China is increasing, and the form of prevention and treatment is exceptionally severe. The clinical treatment of cancer mainly includes surgical treatment, radiotherapy, chemotherapy and targeted therapy. In recent years, cancer immunotherapy has been developing rapidly in the clinic, and its core key is to convert “cold tumors” with low or no response to immunotherapy into “hot tumors” with high immune response, and how to improve the nature of the extracellular space of tumors and establish a new type of efficient drugs via the interstitial pathway, so as to play the role of chemotherapy and chemotherapy. How to improve the nature of tumor extracellular space and establish a new type of high-efficiency drugs via interstitial pathway to play the dual roles of chemotherapy and immunotherapy will bring new breakthroughs in clinical tumor treatment.

To this end, based on the research advantages in medical technology of the Institute of Medical Technology, Peking University, Prof. Han Hongbin's group has actively cooperated with domestic biomedical materials and pharmacy related groups, and has made a series of research progress:

In order to solve the immunosuppressive state of tumor extracellular space, effectively stimulate the tumor immune response, induce long-term immunity, and activate the anti-tumor immune response of distant metastases, Prof. Han Hongbin's group cooperated with Prof. Yu Yingjie of Beijing University of Chemical Technology to develop tumor microenvironment-specific targeting of cationic morpholino platinum oxidative sensitized polymers (PHHM-PhenPt), and formed platinum-containing nanoparticles through self-assembly ( PhenPt NP) by self-assembling to form platinum-containing nanoparticles (PhenPt NP), which increases the accumulation of the drug in the tumor site and reduces the toxic side effects. The PhenPt NPs entering the tumor site can further stimulate the intratumor immune response by activating the cGAS-STING pathway in cancer cells. The above research paper was published in Advanced Functional Materials (impact factor 19.924, Q1 area). Dr. Lingpu Zhang, a doctoral student of Beijing University of Chemical Technology, was the first author, and Dr. Kun Shang, a postdoctoral fellow in Prof. Hongbin Han's group, was the co-first author. Prof. Hongbin Han and Prof. Yingjie Yu of Beijing University of Chemical Technology are the co-corresponding authors.

Figure 1 Schematic diagram of the preparation and chemoimmunization of S-NP-CPT

A) The synthetic route of CPT-SS-SA; B) CPT-SS-SA (with disulfide bond) can be co-assembled with PEG2000-DSPE to form S-NP-CPT (with GSH reactivity); C) S-NP-CPT can induce DNA damage in cancer cells, which can activate cGAS-STING, and cause the tumor immune microenvironment to go from “cold” to “hot” in the Tumor.

In order to achieve precise tumor targeting by nanomedicines in the extracellular interstitial space of tumors, a camptothecin-containing prodrug was designed and synthesized to form GSH-responsive nanoparticles (S-NP-CPT) by self-assembly.S-NP-CPT, with its long half-life in blood circulation and great tumor-targeting ability of CPT, can further promote the maturation of dendritic cells after releasing CPT in tumor cells that increases tumor infiltration of CD8+ T cells, ultimately achieving synergy between chemotherapy and immunotherapy. The paper was published in Advanced Science (impact factor 17.521, Q1). Dr. Lingpu Zhang, a PhD student from Beijing University of Chemical Technology, was the first author, and Prof. Hongbin Han and Postdoctoral Fellow Kun Shang from Institute of Medical Technology, Peking University School of Medicine, and Prof. Chaoyong Liu from Beijing University of Chemical Technology were the co-corresponding authors.

In order to solve the therapeutic challenge of immune cold tumors, Prof. Hongbin Han's group, in collaboration with Prof. Xiangping Li from the Department of Pharmacy, Xiangya School of Medicine, Central South University, developed and synthesized ROS-responsive nanoparticles (NPs), which were further fluorescently labeled with NPs to confirm their aggregation in the tumor extracellular space, and released cisplatin and camptothecin through the nanoparticles to activate the cGAS-STING pathway and induce the maturation of DC cells, promoting the maturation of DC cells and the growth of DC cells. Through the release of cisplatin and camptothecin from the nanoparticles, the cGAS-STING pathway was activated, which induced the maturation of DC cells and promoted the infiltration of CD8+ T cells into the tumor, and ultimately realized the transformation of the immune “cold tumor” to the immune “hot tumor”, and achieved the effect of the combined treatment of chemotherapy and immunotherapy. The paper was published in Biomaterials (impact factor 15.304, Q1). Cao Lei, a master's student of Central South University, is the first author of the paper, and Prof. Han Hongbin and Shang Kun, postdoctoral fellows of Institute of Medical Technology, Peking University Medical School, and Prof. Li Xiangping, Department of Pharmacy, Xiangya School of Medicine, Central South University, are the co-corresponding authors.

The above research results were supported by the Beijing High Precision Discipline Fund. In recent years, our institute has always been oriented to the major clinical problems and needs, and has promoted the cross-fertilization and synergistic research between basic and clinical disciplines, solidly carried out the multidisciplinary teamwork, cross-regional collaboration, and medical-industrial cross-research, and is determined to contribute to the construction of a strong science and technology country, a strong talent country, and a healthy China.