Pulse field ablation electrode with integrated triggerable embedded drug ring

Abstract

This invention discloses a pulsed electric field ablation electrode with an integrated triggerable embedded drug ring, relating to the field of medical device technology. The electrode includes a 3D-printed embedded drug ring, an electrode substrate, an electrode tip, and an annular groove. The electrode tip is located at the end of the electrode substrate and has an annular groove. The 3D-printed embedded drug ring carries an antitumor drug, is fixed to the annular groove, and its outer surface forms a smooth and continuous working surface with the electrode substrate. This invention can simultaneously achieve targeted drug release when a high-voltage pulsed electric field is applied for ablation, integrating pulsed electric field ablation with local drug delivery functions. This solves the problem of the single function of traditional electrodes. In scenarios such as percutaneous or open ablation of liver cancer and endoscopic ultrasound ablation of pancreatic cancer, it can achieve precise synergy between physical ablation and chemotherapy / immunotherapy, effectively improving the tumor treatment effect.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to a pulsed electric field ablation electrode for the ablation treatment of solid tumors, and more particularly to a pulsed electric field ablation electrode with an integrated triggerable embedded drug ring. Background Technology

[0002] Pulsed electric field ablation is a non-thermal local ablation technique that uses high-voltage pulses to create irreversible electroporation in the cell membrane, inducing tumor cell apoptosis. Due to its advantages such as preserving blood vessels and nerves, it has attracted much attention in the treatment of solid tumors such as liver cancer, pancreatic cancer, breast cancer, prostate cancer, and thyroid cancer. The pulsed electric field ablation electrode is the core component for performing this ablation technique.

[0003] However, traditional pulsed electric field ablation electrodes have a single function, only capable of performing simple physical ablation; their main effect is limited to directly destroying tumor cells through electroporation. For malignant tumors, especially those with highly heterogeneous and complex immune microenvironments such as pancreatic cancer, traditional pulsed electric field ablation electrodes have the following limitations: 1) They cannot remove residual infiltrating cancer cells at the edge of the ablation zone, leading to a risk of local recurrence; 2) They are ineffective against distant micrometastases of the tumor; 3) They are difficult to effectively regulate the inhibitory tumor immune microenvironment; thus, drug therapy is still needed as an adjunct to more comprehensively control tumor growth and metastasis.

[0004] Current drug treatments typically involve intravenous or oral administration, but these methods have significant limitations in terms of drug release time and location. After entering the body, drugs must circulate systemically to reach the tumor site, and this delivery method is difficult to effectively synergize with the timing of pulsed electric field ablation. Specifically, pulsed electric field ablation induces electroporation of cell membranes during the ablation process, which is the optimal time window for drug entry into cells. However, traditional drug delivery methods cannot precisely synchronize with the action of the pulsed electric field, preventing the drug from efficiently and directionally reaching tumor cells at this optimal time, thus reducing the effectiveness of drug therapy.

[0005] Therefore, there is an urgent need to develop a new treatment method that combines drug delivery systems with pulsed electric field ablation technology to achieve the synergistic effect of the two. Summary of the Invention

[0006] The purpose of this invention is to address the shortcomings of existing technologies by providing a pulsed electric field ablation electrode with an integrated triggerable embedded drug ring. Its core lies in integrating a 3D-printed embedded drug ring through an annular groove, ensuring that the drug is released in a controllable and targeted manner under the triggering of a high-voltage ablation pulse.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: A pulsed electric field ablation electrode with an integrated triggerable embedded drug ring, comprising: Electrode substrate 2: made of conductive metal material, with an electrode tip 3 for ablation at its distal end, and an annular groove 4 provided on the central surface of the electrode tip 3.

[0008] 3D-printed embedded drug ring 1: Precision manufactured using 3D printing technology from electrically responsive smart materials, its shape matches the annular groove 4, allowing it to be tightly embedded and fixed within the annular groove 4. This drug ring is loaded with an antitumor drug.

[0009] After the 3D-printed embedded drug ring 1 is embedded in the annular groove 4, its outer surface smoothly transitions with the outer surface of the electrode tip 3, forming a continuous and smooth integral working surface without any protrusions or steps.

[0010] Preferably, the depth of the annular groove is 0.1 mm to 0.5 mm and the width is 0.5 mm to 2.0 mm.

[0011] Preferably, the electroresponsive smart material is an electroresponsive material such as polypyrrole composite hydrogel or layered double hydroxide.

[0012] Preferably, the antitumor drug 5 includes a chemotherapy drug, an immunomodulator, or a plasmid encoding an immune factor.

[0013] The beneficial effects of this invention are as follows: (1) Excellent puncture performance and safety: Because the embedded drug ring is perfectly embedded in the annular groove, the overall surface of the electrode is continuous and smooth. This feature makes it less resistant and more precise in interventional procedures such as percutaneous puncture, open surgery or endoscopic ultrasound, which can effectively reduce tissue damage and accidental loss of drugs during intervention, and is especially suitable for the precision treatment of deep tumors (such as pancreatic cancer).

[0014] (2) Synchronized and synergistic therapy: The 3D-printed embedded drug ring is configured to simultaneously release drugs at specific points when a high-voltage pulsed electric field for tissue ablation is applied. This design achieves a natural temporal and spatial synergy between cell electroporation and drug delivery, maximizing the use of the window of enhanced cell membrane permeability to enable efficient drug entry into cells and achieve "electrochemical sensitization." If the released drug is an immune adjuvant, it can work in situ with tumor antigens to form a "vaccine effect," activating systemic immunity to clear residual lesions and micrometastases.

[0015] (3) Modularization and standardization: 3D printed embedded drug rings can be used as standardized consumables for pre-filled drugs. They are produced and sterilized separately from electrodes and assembled before use, which improves the flexibility and convenience of clinical applications. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the electrode structure of the present invention without the 3D-printed embedded drug ring; Figure 2 This is a schematic diagram of the electrode structure for loading a 3D-printed embedded drug ring according to the present invention; Figure 3 This is a partially enlarged schematic diagram of the electrode of the present invention, which is loaded with a 3D-printed embedded drug ring; Figure 4 This is a schematic diagram illustrating the release of drug by a 3D-printed embedded drug ring loaded with the present invention under the action of an electric field; The diagram shows: 3D printed embedded drug ring-1, electrode substrate-2, electrode tip-3, annular groove-4, and antitumor drug-5. Detailed Implementation

[0017] The technical solution of the present invention will be clearly and completely described below with reference to the accompanying drawings and embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0018] In a first aspect, the present invention provides a pulsed electric field ablation electrode with an integrated triggerable embedded drug ring, the schematic diagram of which is shown below. Figure 1 , 2 As shown, it includes: a 3D-printed embedded drug ring 1, an electrode substrate 2, an electrode tip 3, and an annular groove 4.

[0019] Among them, the 3D printed embedded drug ring 1 is precisely manufactured by 3D printing technology using an electrically responsive smart material and is used to load anti-tumor drugs; its shape is perfectly matched with the annular groove 4 and can be tightly embedded and fixed in the annular groove 4; the electrode substrate 2 is made of conductive metal material, and its end is an electrode tip 3 for pulsed electric field ablation, and the surface of the center of the electrode tip 3 is provided with an annular groove 4.

[0020] The 3D-printed embedded drug ring 1 has a movable bayonet. After being embedded in the annular groove 4, the bayonet closes, and its outer surface smoothly transitions with the outer surface of the electrode tip 3, forming a continuous and smooth integral working surface without any protrusions or steps.

[0021] Preferably, the depth of the annular groove is 0.1 mm to 0.5 mm and the width is 0.5 mm to 2.0 mm.

[0022] Preferably, the electroresponsive smart material is an electroresponsive material such as polypyrrole composite hydrogel or layered double hydroxide.

[0023] Preferably, the antitumor drug includes chemotherapeutic drugs, immunomodulators, or plasmids encoding immune factors.

[0024] Secondly, this invention provides a method for using a pulsed electric field ablation electrode with an integrated triggerable embedded drug ring. The overall process consists of three key stages: integrated assembly of the electrode and drug ring, image-guided precise puncture and placement, and simultaneous ablation and drug release triggered by the pulsed electric field. This method, through multidisciplinary fusion design, achieves a high degree of synergy between physical ablation, targeted drug delivery, and immune modulation, significantly improving the efficiency of local tumor treatment and reducing systemic toxicity. Specifically, it includes the following steps: S1: Assembly of 3D-printed embedded drug rings and pulsed electric field ablation electrodes First, such as Figure 1 and Figure 2 As shown, the embedded drug ring is fabricated using high-precision biocompatible 3D printing technology. The drug ring is composed of a smart responsive material with good elasticity and dielectric properties, internally loaded with chemotherapeutic drugs, immunomodulators, or nucleic acid therapeutic molecules, and designed with a precisely matched, movable bayonet structure. Subsequently, the drug ring is embedded into a pre-designed annular groove at the tip of a pulsed electric field ablation electrode. Thanks to the precise control of micron-level dimensions achieved by the 3D printing process and the elastic recovery properties of the material itself, the bayonet automatically closes after embedding, achieving mechanical self-locking. More importantly, as... Figure 3 As shown, the exposed surface of the drug ring is completely flush with the surface of the electrode tip, forming a continuous, smooth, and uniformly conductive working interface. This integrated structure not only ensures the mechanical stability of the electrode during subsequent interventional procedures, preventing the drug ring from falling off due to friction or bending during puncture, but also ensures the uniform distribution of the pulsed electric field in the tumor tissue, preventing the risk of electric field distortion or local overheating caused by uneven surfaces.

[0025] S2: Precision puncture After electrode assembly, the clinical interventional procedure begins. Based on the tumor's location, size, proximity to vital organs, and the patient's individual condition, the most suitable interventional route is selected—including percutaneous puncture, laparoscopic-assisted open surgery, or endoscopic transoral approach. Throughout the puncture, real-time image navigation systems such as ultrasound, CT, MRI, or endoscopic ultrasound are used to dynamically monitor the electrode's trajectory, ensuring its tip accurately reaches the tumor's core area. The aforementioned integrated design results in a highly smooth electrode surface without protrusions or seams, significantly reducing puncture resistance and the risk of tissue tearing, making it particularly suitable for tumors with dense textures or located in areas with high vascularity and nerve density. Furthermore, the electrode's compact structure and moderate flexibility maintain good maneuverability and control even in curved pathways (such as the pancreas, hepatic hilum, or prostate), significantly improving surgical safety and success rates. Once precisely positioned, the electrode is in the optimal treatment location, laying the spatial foundation for subsequent simultaneous ablation and drug delivery.

[0026] S3: Pulsed ablation and simultaneous drug release like Figure 4 As shown, once the electrode is stably placed in the tumor target area, the pulsed electric field ablation system is activated, applying a personalized, optimized sequence of high-voltage short pulses. This non-thermal ablation mechanism induces irreversible electroporation on the cell membrane, disrupting the integrity of the cancer cell membrane, triggering calcium ion influx, mitochondrial dysfunction, and programmed cell death, thereby efficiently eliminating tumor cells while preserving the structure and function of surrounding blood vessels, nerves, and connective tissue to the greatest extent possible.

[0027] Simultaneously, the drug ring embedded in the electrode tip is "activated" under the influence of a localized strong electric field: the internal electroresponsive material undergoes volume expansion or network dissociation due to electrochemical redox, ion migration, or conformational changes, thereby triggering the rapid and controllable release of the loaded drug. The types of drugs released can be flexibly configured according to the tumor type; for example, chemotherapy drugs are used to directly kill residual cancer cells; immunomodulators are used to reshape the tumor immune microenvironment; or nucleic acid drugs are used to target and intervene in oncogenic signaling pathways.

[0028] Crucially, the drug release time window highly coincides with the "electroporation window" induced by the pulsed electric field. Within this brief but critical span of seconds to minutes, tumor cell membrane permeability is significantly enhanced, forming numerous nanoscale hydrophilic channels. This allows large molecular drugs (such as proteins, plasmids, and mRNA) that are normally difficult to cross the membrane to enter the cell efficiently, significantly enhancing drug efficacy. This dual mechanism of "electroporation enhancement + electrotriggered drug release" achieves a precise spatiotemporal coupling between physical destruction and chemo / immunotherapy.

[0029] Example 1: This embodiment provides a method for using a pulsed electric field ablation electrode with an integrated triggerable embedded drug ring in percutaneous or open surgery for liver cancer ablation: S1: Assembly of 3D-printed embedded drug rings and pulsed electric field ablation electrodes First, the embedded drug ring is fabricated using high-precision biocompatible 3D printing technology. This drug ring is composed of a smart responsive material with good elasticity and dielectric properties, internally loaded with chemotherapy drugs, immunomodulators, or nucleic acid therapeutic molecules, and designed with a precisely matched, movable bayonet structure. Subsequently, the drug ring is embedded into a pre-designed annular groove at the tip of the pulsed electric field ablation electrode. Thanks to the precise control of micron-level dimensions achieved by the 3D printing process and the elastic recovery characteristics of the material itself, the bayonet automatically closes after embedding, achieving mechanical self-locking. More importantly, the exposed surface of the drug ring is completely flush with the surface of the electrode tip, forming a continuous, smooth, and uniformly conductive working interface. This integrated structure not only ensures the mechanical stability of the electrode during subsequent interventional procedures, preventing the drug ring from falling off due to friction or bending during puncture, but also ensures the uniform distribution of the pulsed electric field in the tumor tissue, preventing the risk of electric field distortion or localized overheating caused by surface unevenness.

[0030] S2: Precision puncture In this embodiment, precise puncture can be performed via either the percutaneous or open abdominal approach. The specific puncture path is selected based on the actual clinical situation. Percutaneous approach: Under real-time guidance from medical imaging modalities such as ultrasound or CT, the pre-assembled pulsed electric field ablation electrode is inserted through a skin puncture path, passing layer by layer through subcutaneous tissue, abdominal wall muscles, and peritoneum, ultimately reaching the core area of ​​the target tumor within the liver. The entire puncture process is aided by high-resolution imaging feedback to ensure accurate and precise placement of the pulsed electric field ablation electrode at the predetermined target point, minimizing non-specific damage to surrounding normal liver parenchyma and other adjacent organs (such as the gallbladder, diaphragm, and colon).

[0031] Open abdominal approach: Under direct visualization during open abdominal surgery, the surgeon can directly observe the anatomical structures on the surface of the liver. Through an incision in the liver capsule or direct puncture, the pulsed electric field ablation electrode is inserted vertically or obliquely into the liver surface, precisely locating the center of the tumor. This method is particularly suitable for lesions located deep within the liver, adjacent to major blood vessels, or difficult to safely access percutaneously.

[0032] The pulsed electric field ablation electrode used in this invention has a highly smooth geometric shape with a precisely engineered working surface. This not only significantly reduces the risk of tissue traction, tearing, or bleeding caused by friction or structural protrusions during puncture, but also effectively ensures the structural integrity of the 3D-printed embedded drug ring 1 integrated into the proximal end of the electrode throughout the puncture process. This prevents the ring from falling off, shifting, or being worn on the surface when passing through dense tissue or curved paths, thereby ensuring the reliability and consistency of the subsequent drug release function.

[0033] S3: Pulsed ablation and simultaneous drug release After the electrode is precisely punctured and positioned, the treatment procedure is initiated, and pulse ablation and drug release are performed simultaneously.

[0034] Ablation: After precise positioning of the ablation electrode using a pulsed electric field, the system applies a high-voltage nanosecond to microsecond pulsed electric field with optimized parameters. This electric field induces an irreversible electroporation effect within the tumor tissue, disrupting the lipid bilayer structure of the cell membrane and forming nanoscale permanent pores. This process leads to ion imbalance and metabolic collapse inside and outside the cell, ultimately triggering widespread programmed apoptosis and secondary necrosis of tumor cells, resulting in a well-defined ablation zone.

[0035] Drug Release: The 3D-printed embedded drug ring 1, integrated into the pulsed electric field ablation electrode structure, is composed of an electrically responsive smart polymer material (such as a conductive polymer, electrosensitive hydrogel, or dielectric elastomer). A schematic diagram illustrating the drug release when the 3D-printed embedded drug ring 1 is loaded under an electric field is shown below. Figure 4 As shown, when a therapeutic high-voltage pulse is applied, the electric field acts as an external trigger signal, causing conformational changes, swelling, or local degradation in the smart material. This allows for the rapid and controllable release of the anti-tumor drugs, such as chemotherapy drugs, immunomodulators, or plasmids encoding immune factors, loaded within the material within seconds to minutes. These drugs can then be rapidly and precisely released into the ablated tumor area.

[0036] The two processes described above are highly synchronized in time and space, resulting in a synergistic and enhanced anti-tumor effect: Irreversible electroporation induced by pulsed electric field ablation not only directly kills tumor cells but also significantly increases the cell membrane permeability of residual tumor cells and infiltrating immune cells (such as dendritic cells and T cells), creating a brief "electroporated window." During this window, high-concentration drugs released from the 3D-printed embedded drug ring 1 can efficiently penetrate the permeabilized cell membrane and enter the cell to exert their pharmacological effects. Among these, chemotherapy drugs can directly enhance cytotoxicity; immunomodulators can effectively activate local anti-tumor immune responses; and nucleic acid drugs can achieve in situ gene expression and immune reprogramming. Thus, physical ablation and chemotherapy / immunotherapy are highly coupled in space and time, producing a synergistic anti-tumor effect greater than the sum of its parts (1+1>2).

[0037] Example 2: This embodiment provides a method for using a pulsed electric field ablation electrode with an integrated triggerable embedded drug ring for pancreatic cancer ablation under endoscopic ultrasound guidance: S1: Assembly of 3D-printed embedded drug rings and pulsed electric field ablation electrodes First, the embedded drug ring is fabricated using high-precision biocompatible 3D printing technology. This drug ring is composed of a smart responsive material with good elasticity and dielectric properties, internally loaded with chemotherapy drugs, immunomodulators, or nucleic acid therapeutic molecules, and designed with a precisely matched, movable bayonet structure. Subsequently, the drug ring is embedded into a pre-designed annular groove at the tip of the pulsed electric field ablation electrode. Thanks to the precise control of micron-level dimensions achieved by the 3D printing process and the elastic recovery characteristics of the material itself, the bayonet automatically closes after embedding, achieving mechanical self-locking. More importantly, the exposed surface of the drug ring is completely flush with the surface of the electrode tip, forming a continuous, smooth, and uniformly conductive working interface. This integrated structure not only ensures the mechanical stability of the electrode during subsequent interventional procedures, preventing the drug ring from falling off due to friction or bending during puncture, but also ensures the uniform distribution of the pulsed electric field in the tumor tissue, preventing the risk of electric field distortion or localized overheating caused by surface unevenness.

[0038] S2: Precision puncture Under the high-resolution real-time imaging guidance of endoscopic ultrasound, the assembled pulsed electric field ablation electrode is punctured through the working channel of the endoscope via the stomach wall or duodenal wall, crossing the digestive tract mucosa, muscle layer and serosa, to precisely reach the target area of ​​the pancreatic tumor.

[0039] The interventional pathway is complex and the channel is narrow and tortuous, requiring the pulsed electric field ablation electrode to possess excellent flexibility, delivery capability, and bending resistance. Thanks to the ultra-smooth engineered surface treatment of the pulsed electric field ablation electrode, it experiences minimal resistance when passing through the narrow and tortuous working channel of the endoscope, ensuring smooth operation and significantly reducing the risk of instrument jamming or channel damage. Simultaneously, the smooth surface greatly reduces additional mechanical stimulation and trauma to sensitive structures such as the gastric / intestinal wall and peripancreatic nerves and blood vessels during puncture, thereby improving the surgical safety and patient tolerability of endoscopic interventional procedures.

[0040] S3: Pulsed ablation and simultaneous drug release After the electrode is precisely punctured and positioned, the treatment procedure is initiated, and pulse ablation and drug release are performed simultaneously.

[0041] After EUS confirms that the pulsed electric field ablation electrode is stably located in the center of the pancreatic tumor, the system applies a high-voltage pulse signal (such as multi-phase, frequency conversion, gradient voltage, etc.) specifically optimized for pancreatic tissue characteristics (such as high fibrosis and low conductivity) to overcome the dense stromal barrier unique to pancreatic cancer.

[0042] Ablation: The optimized pulsed electric field can effectively penetrate the fibrotic matrix of pancreatic cancer, inducing the formation of a uniform, irreversible electroporation region within the tumor parenchyma. This process directly destroys the structure of cancer cells and simultaneously triggers the death of immune stem cells, releasing a large number of tumor-associated antigens and damage-associated molecular patterns, thereby initiating an in situ "vaccine" effect locally and creating conditions for activating a systemic anti-tumor immune response.

[0043] Drug release: A schematic diagram illustrating the release of drug by loading a 3D-printed embedded drug ring 1 under the influence of an electric field is shown below. Figure 4 As shown, the 3D-printed embedded drug ring 1 responds to a high-voltage pulse signal, and its smart material matrix undergoes controllable physicochemical changes, thereby rapidly and precisely releasing the loaded anti-tumor drugs (such as chemotherapy drugs, immunomodulators, or plasmids encoding immune factors) to the ablated tumor area.

[0044] This embodiment addresses the unique microenvironmental barriers of pancreatic cancer by constructing a multi-stage synergistic treatment strategy: pulsed ablation first physically dismantles the highly dense fibrous interstitial network of pancreatic cancer, breaking down its physical barriers to drug penetration and immune cell infiltration; ablation-induced immunogenic cell death releases neoantigens, creating a "hot tumor" microenvironment. Based on this, the locally released high-concentration drug can rapidly act on exposed tumor cells and immune cells, directly killing residual lesions on one hand, and powerfully activating adaptive immune responses on the other. This three-pronged strategy of "barrier breaking—drug release—activation" achieves deep integration and synergistic effects of physical ablation, drug delivery, and immune regulation in the treatment of pancreatic cancer, a refractory tumor.

[0045] In summary, regardless of the application scenario, this invention can achieve simultaneous "physical ablation and chemical / immune intervention". Its smooth surface design ensures the precision and safety of the intervention process, while the "high-voltage pulse synchronous triggering drug release" mechanism ensures precise spatial and temporal control of the therapeutic drug, ultimately achieving a synergistic therapeutic effect.

Claims

1. A pulsed electric field ablation electrode with an integrated triggerable embedded drug ring, characterized in that, include: The electrode substrate (2) has an electrode tip (3) for ablation at its distal end, and an annular groove (4) is formed on the central surface of the electrode tip (3). A 3D-printed embedded drug ring (1) is precisely manufactured by 3D printing technology from an electrically responsive smart material. Its shape matches the annular groove (4) and can be tightly embedded and fixed in the annular groove (4). The drug ring is loaded with an anti-tumor drug (5). After the 3D printed embedded drug ring (1) is embedded in the annular groove (4), its outer surface smoothly transitions with the outer surface of the electrode tip (3), forming a continuous and smooth overall working surface without any protrusions or steps.

2. The pulsed electric field ablation electrode according to claim 1, characterized in that, The electrode substrate (2) is made of conductive metal material.

3. The pulsed electric field ablation electrode according to claim 1, characterized in that, The 3D-printed embedded drug ring (1) has a movable bayonet structure; the electrically responsive smart material includes polypyrrole composite hydrogel and layered hydroxide.

4. The pulsed electric field ablation electrode according to claim 1, characterized in that, The antitumor drugs (5) include chemotherapeutic drugs, immunomodulators, or plasmids encoding immune factors.

5. The pulsed electric field ablation electrode according to claim 1, characterized in that, The annular groove (4) has a depth of 0.1 mm to 0.5 mm and a width of 0.5 mm to 2.0 mm.

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