From model construction to efficacy verification: Stereotactic brain positioning system supports sequential targeted sonodynamic nanovaccination to solve the problem of GBM treatment
Date：2025-09-15
Author：
Brain tumor treatment has always been a major medical challenge. With the advancement of medical research, various new treatments are constantly emerging. Recently, a research team from Shanghai Jiao Tong University published an article in ACS Nano titled "Noninvasive Activation of Local and Systemic Immunity with a Sequential-Targeting Sonodynamic Nanovaccine to Treat Glioblastoma," introducing a new treatment approach that may provide new insights and directions for the treatment of brain tumors and other types of tumors.
02. Non-invasive direct tumor ablation
As an emerging non-invasive treatment, Stars NV vaccine generates cytotoxic reactive oxygen species (ROS) in tumor tissue under ultrasound stimulation, directly killing GBM cells.Researchers successfully established a mouse glioblastoma model using the Yuyan Instruments stereotaxic device and treated GBM mice with Stars NV combined with ultrasound (US).
The results showed that the bioluminescence signal of mice in the Stars NV combined with ultrasound (US) treatment group remained at a low level (exponentially increased in the control group), and could also trigger ICD by inducing the release of endogenous damage-associated molecular patterns (DAMPs), such as calreticulin (CRT) translocation and ATP secretion.
03. Comprehensive remodeling of the immune microenvironment
Under ultrasound stimulation, Stars NV not only ablates GBM in a non-invasive manner, induces adaptive anti-GBM immune response, and plays the role of personalized in situ vaccine,.It can also release R848 to reprogram the inhibitory TIME microenvironment, activate systemic immunity, and promote T cell production in the thymus.
Compared with the saline control group, Stars NV treatment increased the ratio of M1/M2 tumor-associated macrophages (TAMs) by 31-fold, tumor-infiltrating lymphocytes (TILs) by 5.2-fold, CD4 T cells by 4.8-fold, and CD8 T cells by 9.7-fold, while regulatory T cells (Tregs) in the local TIME microenvironment decreased by 5.5-fold.
The combination therapy extended the median survival of mice with intracranial GBM from 23 days to at least 60 days. Furthermore, Stars NV therapy effectively promoted the formation of immune memory in treated mice, potentially enhancing their resistance to GBM recurrence.
04. Brain function improvement and safety
Glioblastomas often compress normal brain tissue, and invasive surgery carries a high risk of neuronal damage.Both conditions may affect the motor function of mice.To verify the safety and efficacy of Stars NV vaccine treatment, the research team conducted a series of behavioral experiments.
Behavioral experiments (rotarod test and open field test) showed that the motor coordination and balance ability of mice in the Stars NV+US treatment group were improved, and their exploratory behavior in the new environment was more active; while the saline group showed discomfort characteristics such as emotional distress and reduced activity, confirming that this regimen has both anti-tumor efficacy and safety.
"Sequential targeting" design (pH-sensitive ligand switching) provides a new paradigm for cross-barrier drug delivery and cell-specific targeting; ultrasound-triggered "on-demand drug release" combined with SDT reduces off-target toxicity and improves precision;
03. Clinical translation potential
Its non-invasive nature, high biocompatibility (no significant organ toxicity), and significantly prolonged survival make it a promising candidate for clinical translation, potentially improving patient prognosis and reducing recurrence rates.
04. Immunotherapy Implications
Studies have confirmed that remodeling local TIME alone is not enough to control GBM, and systemic immunity must be activated simultaneously to replenish T cell reserves. This provides an important reference for the immunotherapy of other "cold tumors" (such as pancreatic cancer and liver cancer) - the synergistic strategy of "local microenvironment remodeling + systemic immune activation" may become a broad-spectrum anti-tumor solution.
In the study, researchers used the Yuyan Instruments brain stereotaxic instrument to successfully construct a mouse glioblastoma model, confirming the anti-tumor efficacy of Stars NV.
01. Large digital display screen, touch control
Equipped with a 4.3-inch digital display, the data display is clearer; the display brightness can be adjusted steplessly, and the best display effect can be achieved regardless of the external light brightness;
02. Zero adjustment function, easy to operate
The X, Y, and Z axis moving distances are displayed in real time on the screen. Users can read the data directly without checking the data before and after, with an accuracy of 10μm.
03.Classic design, precise control
Self-developed core creates extraordinary strength
Shanghai Yuyan Scientific Instrument Co., Ltd., as a leading manufacturer of scientific research equipment in the industry, has been adhering to the core concept of "innovation-driven development and self-research to create high-quality products" for 15 years since its establishment in 2010. It is committed to the independent research and development and production of scientific instruments. Its current product line covers multiple scientific research and application fields such as experimental animal husbandry, physiological signal acquisition, and neuroscience research. Not only does it continuously optimize and upgrade conventional instruments, but it also dares to explore cutting-edge technologies and has launched a series of high-end scientific instruments with independent intellectual property rights.
The company's R&D personnel account for 40%, and it has a team of scientists in sensors, chip design, core algorithms, etc., and has professional teams to provide support in product implementation and operation, market and academic promotion, comprehensive product solution design and application. The company has service points covering the whole country and strong technical service capabilities. Its customers include Tsinghua University, Peking University, Zhejiang University, Shanghai Jiaotong University, University of Chinese Academy of Sciences, West China Hospital of Sichuan University, Northern Theater Command General Hospital and other first-class research institutions and hospitals at home and abroad.
Background
Glioblastoma (GBM) is the most aggressive malignant tumor of the central nervous system. Its treatment faces multiple challenges: the blood-brain barrier (BBB) hinders drug delivery, the tumor immune microenvironment (TIME) is highly suppressive, and systemic immunosuppression occurs. Existing therapies result in a median survival of only approximately 15 months, a 5-year survival rate of less than 6%, and a recurrence rate of nearly 100%. While immunotherapy holds great promise, GBM is a "cold" tumor whose immune microenvironment severely restricts T cell infiltration and activation, limiting its efficacy.
The "Sequential Targeted Sonodynamic Nanovaccine (Stars NV)" developed by the research team synergistically addresses the challenges of GBM treatment through multiple mechanisms, and has both significant anti-tumor effects and good safety.
Core Features
Stars NV is surface-modified with BBB-penetrating ligands (such as T7 peptides) to evade clearance by the mononuclear phagocytic system (MPS) in the blood. After efficiently crossing the BBB, it sheds BBB ligands under the acidic conditions of the tumor microenvironment, exposing macrophage targeting sites and accurately binding to M2 TAMs.
02. Non-invasive direct tumor ablation
As an emerging non-invasive treatment, Stars NV vaccine generates cytotoxic reactive oxygen species (ROS) in tumor tissue under ultrasound stimulation, directly killing GBM cells.Researchers successfully established a mouse glioblastoma model using the Yuyan Instruments stereotaxic device and treated GBM mice with Stars NV combined with ultrasound (US).
The results showed that the bioluminescence signal of mice in the Stars NV combined with ultrasound (US) treatment group remained at a low level (exponentially increased in the control group), and could also trigger ICD by inducing the release of endogenous damage-associated molecular patterns (DAMPs), such as calreticulin (CRT) translocation and ATP secretion.
03. Comprehensive remodeling of the immune microenvironment
Under ultrasound stimulation, Stars NV not only ablates GBM in a non-invasive manner, induces adaptive anti-GBM immune response, and plays the role of personalized in situ vaccine,.It can also release R848 to reprogram the inhibitory TIME microenvironment, activate systemic immunity, and promote T cell production in the thymus.
Compared with the saline control group, Stars NV treatment increased the ratio of M1/M2 tumor-associated macrophages (TAMs) by 31-fold, tumor-infiltrating lymphocytes (TILs) by 5.2-fold, CD4 T cells by 4.8-fold, and CD8 T cells by 9.7-fold, while regulatory T cells (Tregs) in the local TIME microenvironment decreased by 5.5-fold.
The combination therapy extended the median survival of mice with intracranial GBM from 23 days to at least 60 days. Furthermore, Stars NV therapy effectively promoted the formation of immune memory in treated mice, potentially enhancing their resistance to GBM recurrence.
04. Brain function improvement and safety
Glioblastomas often compress normal brain tissue, and invasive surgery carries a high risk of neuronal damage.Both conditions may affect the motor function of mice.To verify the safety and efficacy of Stars NV vaccine treatment, the research team conducted a series of behavioral experiments.
Behavioral experiments (rotarod test and open field test) showed that the motor coordination and balance ability of mice in the Stars NV+US treatment group were improved, and their exploratory behavior in the new environment was more active; while the saline group showed discomfort characteristics such as emotional distress and reduced activity, confirming that this regimen has both anti-tumor efficacy and safety.
Mechanism Summary
Stars NV innovatively integrates direct tumor ablation, local TIME reprogramming, adaptive immune activation and systemic T cell promotion mechanisms to form a synergistic effect, providing a safe and non-invasive treatment option for GBM, effectively inhibiting tumor progression and maintaining brain function.Research significance
01. Solve the core pain points of GBM treatmentThis is the first synergistic treatment to achieve "non-invasive BBB breakthrough + precise targeting of TAMs + simultaneous activation of local and systemic immunity," overcoming the three major challenges of the BBB barrier, immunosuppressive microenvironment, and systemic T cell deficiency, providing a "one-stop" solution.
"Sequential targeting" design (pH-sensitive ligand switching) provides a new paradigm for cross-barrier drug delivery and cell-specific targeting; ultrasound-triggered "on-demand drug release" combined with SDT reduces off-target toxicity and improves precision;
03. Clinical translation potential
Its non-invasive nature, high biocompatibility (no significant organ toxicity), and significantly prolonged survival make it a promising candidate for clinical translation, potentially improving patient prognosis and reducing recurrence rates.
04. Immunotherapy Implications
Studies have confirmed that remodeling local TIME alone is not enough to control GBM, and systemic immunity must be activated simultaneously to replenish T cell reserves. This provides an important reference for the immunotherapy of other "cold tumors" (such as pancreatic cancer and liver cancer) - the synergistic strategy of "local microenvironment remodeling + systemic immune activation" may become a broad-spectrum anti-tumor solution.
In the study, researchers used the Yuyan Instruments brain stereotaxic instrument to successfully construct a mouse glioblastoma model, confirming the anti-tumor efficacy of Stars NV.
Key equipment for brain science research
The Yuyan Brain Stereotaxic System utilizes the anatomical characteristics of brain structure and coordinate positioning principles to pinpoint the location of target areas within the brain by fixing the experimental animal's head and using specific coordinate parameters. This device can precisely locate different nuclei, tissues, or lesions within the brain, enabling more accurate injection, stimulation, and lesion manipulation of the experimental animal's brain, thereby accurately exploring the impact of different brain structures on the animal's physiological and pathological processes.
01. Large digital display screen, touch control
Equipped with a 4.3-inch digital display, the data display is clearer; the display brightness can be adjusted steplessly, and the best display effect can be achieved regardless of the external light brightness;
02. Zero adjustment function, easy to operate
The X, Y, and Z axis moving distances are displayed in real time on the screen. Users can read the data directly without checking the data before and after, with an accuracy of 10μm.
03.Classic design, precise control
The cross arm has been upgraded to a three-rod fixed design with two-way penetration, which always maintains two fulcrums on both sides for precise and stable operation. The classic U-shaped base design has a simple and exquisite appearance, and is easy and flexible to install and adjust.
Self-developed core creates extraordinary strength
Shanghai Yuyan Scientific Instrument Co., Ltd., as a leading manufacturer of scientific research equipment in the industry, has been adhering to the core concept of "innovation-driven development and self-research to create high-quality products" for 15 years since its establishment in 2010. It is committed to the independent research and development and production of scientific instruments. Its current product line covers multiple scientific research and application fields such as experimental animal husbandry, physiological signal acquisition, and neuroscience research. Not only does it continuously optimize and upgrade conventional instruments, but it also dares to explore cutting-edge technologies and has launched a series of high-end scientific instruments with independent intellectual property rights.
The company's R&D personnel account for 40%, and it has a team of scientists in sensors, chip design, core algorithms, etc., and has professional teams to provide support in product implementation and operation, market and academic promotion, comprehensive product solution design and application. The company has service points covering the whole country and strong technical service capabilities. Its customers include Tsinghua University, Peking University, Zhejiang University, Shanghai Jiaotong University, University of Chinese Academy of Sciences, West China Hospital of Sichuan University, Northern Theater Command General Hospital and other first-class research institutions and hospitals at home and abroad.