3DPTimes — One World Printed Together

September 16, 2025 Applications The Fourth Affiliated Hospital, Zhejiang University School of Medicine 13

A 3D-printed collar that enhances radiofrequency ablation (RFA) into potent thermal immunotherapy for lung cancer, boosting both local heat coverage and systemic immune response.

Lung cancer has the highest incidence and mortality rates among malignant tumors worldwide. Radiofrequency ablation (RFA), as a minimally invasive treatment, has been widely adopted in clinical practice due to its advantages of minimal trauma and rapid recovery. It uses high-frequency electrical currents to generate heat, directly "burning out" tumor cells. However, clinically, challenges such as irregular tumor morphology often lead to incomplete treatment, with some patients experiencing local recurrence or disease progression. Enhancing the efficacy of RFA has thus become an urgent clinical challenge.

In September 2025, a team led by Professor Wang Kai, Director of the Fourth Affiliated Hospital of Zhejiang University School of Medicine and the Zhejiang Provincial Key Laboratory of Precision Diagnosis and Treatment for Lung Cancer, published a research paper titled "A Synergistic 3D-Printed Collar Transforms Radiofrequency Ablation Into Potent Thermal Immunotherapy for Lung Cancer" in the internationally top-tier materials science journal Advanced Materials. The study innovatively proposes a solution: a 3D-printed thermal immunotherapy auxiliary collar (3D-LC12).

The first corresponding author of the paper is Professor Wang Kai, whose research focuses on the mechanisms of lung cancer development and drug resistance evolution, the lung cancer immune microenvironment, and biomarkers for immunotherapy. The second corresponding author is Professor Cai Weibo from the University of Wisconsin-Madison, who primarily engages in research on molecular imaging and bionanotechnology. Researcher Chen Weiyu from the Fourth Affiliated Hospital of Zhejiang University School of Medicine is the first author. This study was supported by funding from the Key Program of the National Natural Science Foundation of China.

The designed "3D-printed collar" can be mounted on the radiofrequency ablation (RFA) needle and inserted simultaneously. It enables precise release of immunotherapeutic drugs, enhances the thermal effect of RFA, and activates immune responses within the tumor microenvironment. This approach successfully improves the overall efficacy of lung cancer treatment, offering a novel therapeutic strategy to enhance treatment outcomes and reduce the risk of recurrence.

Core Breakthrough:
A Single "Collar" Achieves Dual "Thermal + Immunological" Attack

Traditional radiofrequency ablation technology works by generating high temperatures through radiofrequency energy to "burn out" tumor cells. However, it has two major limitations: first, heat is easily dissipated by blood flow, making it difficult to cover irregularly shaped tumors; second, it only eliminates locally visible tumors and fails to activate the immune system to combat potential metastatic foci.

The 3D-LC12 collar designed by Professor Wang Kai’s team is essentially a novel multifunctional immunotherapy platform that combines "smart drug delivery + thermal effect enhancement." Its core innovation lies in integrating magnesium-aluminum layered double hydroxide (LDHs) nano-adjuvants with immune stimulants (CpG and IL-12) and using 3D printing technology to create a collar-shaped carrier that conforms to the tumor.

During treatment, the collar simultaneously achieves two key functions:

Schematic Diagram of the 3D-Printed Nano-Adjuvant Collar (3D-LC12) Combined with RFA

➊ Effectively Enhances Thermal Therapy, Achieving More Thorough "High-Temperature Tumor Destruction"
The LDHs nanomaterials respond to the radiofrequency electric field, acting like "thermal conductive sheets" to improve local heat conduction efficiency, expand the coverage of thermal therapy, and enhance the thermal effect of RFA. Simultaneously, it remodels the tumor microenvironment (TME) to activate anti-tumor immune responses.

Experiments showed that in porcine lung tissue models, the heating area of RFA combined with LDHs increased by approximately 1.4 times compared to traditional methods, effectively covering irregular tumor regions and avoiding "missed targets." Additionally, LDHs protect the immune stimulants from degradation under high temperatures, ensuring their sustained functionality.

➋ Activates the Immune System, Enabling the "Body to Attack Tumors on Its Own"
During thermal therapy, the collar releases immune-stimulating molecules CpG and pIL-12 in response to temperature changes, enhancing the immune system’s attack on tumors: the former activates dendritic cells (the "scouts" of the immune system), while the latter promotes the activation of killer T cells and M1-type macrophages (the "soldiers" of the immune system). These immune cells not only clear locally residual tumor cells but also inhibit the growth of distant metastatic foci, achieving a dual effect of "local treatment + systemic protection."

Experimental Validation:
Significant Efficacy Improvement from Cellular to Animal Models

Through a step-by-step research approach encompassing "in vitro cell experiments → animal model validation," the team confirmed the effectiveness of the 3D-LC12 collar combined with RFA.

3D-Printed Nano-Adjuvant Collar (3D-LC12) Enables Integrated Therapy

➊ In Vitro Experiments: Efficient Activation of the Immune System
Cellular-level studies revealed that LDHs nano-adjuvants significantly promote the transformation of "pro-tumor" M2-type macrophages into "anti-tumor" M1-type macrophages and increase the expression of pro-inflammatory cytokines such as TNF-α and CXCL9 (these factors recruit more immune cells to aggregate at the tumor site). Meanwhile, the activation efficiency of dendritic cells was also markedly improved, laying the foundation for subsequent immune responses.

➋ Animal Experiments: Tumor Growth Suppressed, Survival Extended
In mouse models of lung cancer, the tumor growth rate in the "RFA + 3D-LC12 Collar" group was significantly slower than that in the traditional RFA group, and the survival period of the mice was markedly prolonged. More importantly, this combined therapy demonstrated an "abscopal effect"—the volume of distant tumors was significantly reduced. The new therapy was able to stimulate a strong systemic immune response, thereby inhibiting the growth of untreated distant tumors. This is because activated immune cells travel through the bloodstream to various parts of the body, "hunting down" potentially metastatic tumor cells.

➌ Immune Activation: Mobilizing 'Immune Warriors' to Attack Tumors
Experiments found that after treatment with RFA combined with the 3D-LC12 collar, the number of immune cells with anti-tumor effects, such as M1-type macrophages and CD8+ T cells, significantly increased in both locally treated tumors and distant untreated tumors. This indicates that the combined therapy effectively stimulates a systemic immune response, enabling the body's "immune warriors" to more precisely attack tumor cells, providing critical support for inhibiting tumor spread.

Currently, this technology holds broad clinical prospects: 3D printing enables "precise customization," and the collar can be used simultaneously with RFA surgery without additional trauma, aligning with the trend of minimally invasive therapy. For patients with advanced lung cancer who cannot tolerate surgical resection, elderly and frail patients, or those with tumors in特殊 locations (e.g., near major blood vessels) unsuitable for traditional surgery, this combined therapy of "RFA + 3D-LC12 collar" is expected to become a safer and more effective treatment option.

Team Introduction

The Respiratory Medical Center of the Fourth Affiliated Hospital of Zhejiang University School of Medicine is composed of the Department of Respiratory and Critical Care Medicine, Department of Cardiothoracic Surgery, Department of Radiology, and Department of Pathology. The center currently has 85 physicians, including 27 senior titles, 2 doctoral supervisors, 6 master's supervisors, and 9 specially appointed researchers. In 2023, the annual outpatient volume reached over 130,000 visits, and the annual surgical volume exceeded 2,000 procedures, with bronchoscopic interventional therapy ranking among the top in the province. It is the first training base for lung tumor ablation technology of the Chinese Medical Doctor Association in Zhejiang Province.

The Zhejiang Provincial Key Laboratory of Precision Diagnosis and Treatment for Lung Cancer was established in July 2024 as the only provincial-level key laboratory in the field of lung cancer recognized in Zhejiang Province. It is hosted by the Fourth Affiliated Hospital of Zhejiang University School of Medicine and leverages the joint construction advantages of the hospital, the Hangzhou Institute of Advanced Studies of the University of Chinese Academy of Sciences, and Huadong Medicine Co., Ltd., integrating the three units' rich clinical resources, advanced foundational platforms, and strong R&D capabilities.

The laboratory is directed by Professor Wang Kai and co-directed by Professor Song Hai. Over the past three years, the laboratory has published 171 SCI papers as first/corresponding authors in internationally renowned journals in the field, including Nature Cell Biology, Nature Cancer, Molecular Cell, Cell Reports, Cancer Cell, Journal of Clinical Investigation, and Advanced Materials. It has hosted 39 national projects, including National Science and Technology Major Projects, National Key R&D Programs, Key and General Programs of the National Natural Science Foundation of China, as well as several provincial and ministerial projects such as the Zhejiang Provincial Key R&D Program, with total funding of approximately 80 million RMB. The laboratory has been granted over 20 international and national invention patents and has received awards including the National Science and Technology Progress Award (Second Class), the First Prize of the Ministry of Education's Outstanding Scientific Research Achievements, the Zhejiang Provincial Science and Technology Progress Award (First Class), and the Zhejiang Provincial Youth Science and Technology Award.

Corresponding Author: Wang Kai

Wang Kai, Professor, Chief Physician, Doctoral Supervisor, Qiushi Distinguished Professor of Zhejiang University, Chief Scientist of the National Key R&D Program, Leading Health Talent of Zhejiang Province, and recipient of the State Council Special Allowance. He currently serves as Secretary of the Party Committee of the Fourth Affiliated Hospital of Zhejiang University School of Medicine and the "Belt and Road" International Medical School, and concurrently serves as Director of the Zhejiang Provincial Key Laboratory of Precision Diagnosis and Treatment for Lung Cancer. His academic appointments include Vice Chair-Elect of the Respiratory Disease Branch of the Zhejiang Medical Association, Vice Chair-Elect of the Lung Cancer Professional Committee of the Zhejiang Anti-Cancer Association, and Vice Chair of the Hypoxic Tumorology Professional Committee of the Chinese Anti-Cancer Association. He also serves as an editorial board member for international journals such as Cancer Letters. His research focuses on the mechanisms of lung stem cell regulation in chronic lung diseases and the development of novel intervention technologies, mechanisms of efficacy in targeted and immunotherapy for lung cancer, and the regulation of the lung cancer microenvironment and development of new anti-cancer drugs.

First Author: Chen Weiyu

Chen Weiyu, Ph.D., Researcher at the "Belt and Road" International Medical School of Zhejiang University and the Fourth Affiliated Hospital of Zhejiang University School of Medicine, Provincial-Level Talent of Zhejiang Province, Leading Talent of Jinhua's "Shuanglong Plan," and Deputy Director (Head) of the Scientific Research Department. She specializes in precision diagnosis and efficient treatment strategies for lung cancer and other tumors. Over the past five years, she has published 25 papers as first/corresponding author (including co-author) in internationally renowned journals, including Nature Communications, Advanced Materials, ACS Nano, Advanced Science, and European Journal of Nuclear Medicine and Molecular Imaging. She has presided over four national and provincial-level projects, including the National Natural Science Foundation of China, the Zhejiang Provincial Natural Science Foundation Key Program, and a sub-project of Zhejiang's "Vanguard" Program. Her research results have led to three national invention patent applications, and she has received the Zhejiang Provincial Science and Technology Progress Award (First Class) and the Jinhua City Youth Science and Technology Award.