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Advanced Healthcare Materials · 2024 · IF 10

In Situ Fabrication of Electrospun Magnetic Film Under Laparoscopic Guidance for Preventing Postoperative Recurrence of Hepatocellular Carcinoma

Luyao Xiang,Jinlong Hu,Xu Yan,Huai Yang,Chaofei Ji,Yunjun Xu,Haojie Lu,Chaowei Lu,Qingbing Hou,Yonghong Song,Dongquan Liu,Baoqiang Cao,Yang Lu

Despite laparoscopic-guided minimally invasive hepatectomy emerging as the primary approach for resecting hepatocellular carcinoma (HCC), there's still a significant gap in suitable biomaterials that seamlessly integrate with these techniques to achieve effective hemostasis and suppress residual tumors at the surgical margin. Electrospun films are increasingly used for wound closure, yet the employment of prefabricated electrospun films for hemostasis during minimally invasive HCC resection is hindered by prolonged operation times, complexity in implementation, limited visibility during surgery, and inadequate postoperative prevention of HCC recurrence. In this study, we integrated montmorillonite-iron oxide sheets into the PVP polymer framework, enhancing the resulting electrospun polyvinylpyrrolidone (PVP) /montmorillonite-iron oxide (MI) film (abbreviated as PMI) with robustness, hemostatic capability, and magnetocaloric properties. In contrast to the in vitro prefabricated electrospun films, the electrospun PMI film is designed to be formed in situ on liver wounds under laparoscopic guidance during hepatectomy. This design affords superior wound adaptability, facilitating meticulous wound closure and expeditious hemostasis, thereby simplifying the operative process and ultimately alleviating the workload of healthcare professionals. Moreover, when exposed to an alternating magnetic field, the film can efficiently ablate residual tumors, significantly augmenting the treatment efficacy of HCC. This article is protected by copyright. All rights reserved

研究领域: 生物医学工程 · 肿瘤学 · 外科手术
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Nanomaterials · 2025 ·Vol. 15 ·期 9 ·670 · IF 4.3

A Janus Amyloid-like Nanofilm Inhibits Colorectal Cancer Postoperative Recurrence and Abdominal Adhesion via Synergistic Enzyme Cascade

Man Zhang,Junhao Kou,Zhenyi Song,Ling Qiu,Chunzhao Yang,Qi Xue

Postoperative peritoneal adhesion and high recurrence rates are critical challenges in the clinical treatment of colorectal cancer. In this study, based on amyloid-like protein self-assembly technology, a novel Janus protein film was developed. The protein film encapsulates glucose oxidase (GOx) and catalase (CAT), which is named PTL@GC. Through a one-step method involving cysteine-reduced lysozyme-induced amyloid-like self-assembly, the film was co-loaded with GOx and CAT to achieve synergistic anti-adhesion and anti-tumor recurrence effects. The Janus film features a hydrophobic side that stably adheres to the intestinal surface without exogenous chemical modification and a hydrophilic side that prevents adhesion. The loaded GOx selectively induces disulfidptosis in SLC7A11-overexpressing tumor cells, while CAT degrades H2O2to alleviate hypoxia and inhibit oxidative stress, significantly reducing adhesion-related fibrosis. The experimental results demonstrate that PTL@GC exhibited excellent mechanical properties, high enzyme activity retention (>90%), and controllable degradability (complete metabolism within 50 days). In animal models, PTL@GC reduced postoperative adhesion area by 22.77%, decreased local tumor burden to 28.42% of the control group, and achieved an inhibition rate of 58.49%, without inducing systemic toxicity. This study presents a biologically safe and functionally synergistic approach to addressing dual complications following colorectal cancer surgery, offering potential insights for future research on multifunctional Janus materials.

研究领域: 生物医学工程 · 肿瘤学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioactive Materials · 2024 · IF 18

Preventing postsurgical colorectal cancer relapse: A hemostatic hydrogel loaded with METTL3 inhibitor for CAR-NK cell therapy

Zilin Tan,Liangjie Tian,Yang Luo,Kexin Ai,Xuehua Zhang,Haitao Yuan,Jinfan Zhou,Guangyao Ye,Shuofei Yang,Ming Zhong,Gaohua Li,Yanan Wang

Colorectal cancer (CRC) recurrence post-surgery remains a major challenge. While Chimeric Antigen Receptor (CAR)-engineered natural killer (NK) cells hold immense therapeutic potential, their intratumoral infiltration ability remains limited, hampering efficacy. Building upon prior research suggesting that chemokines like C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10) recruit CAR-NK cells, we hypothesized that tumor cell m6A methylation, regulated by Methyltransferase-like 3 (METTL3), influences chemokine secretion. This study aims to elucidate the underlying mechanisms and improve METTL3 inhibition efficiency. We designed an adhesive hemostasis hydrogel loaded with STM2457, a METTL3 inhibitor, aimed at sustained release in the acidic tumor microenvironment. In vitro, the hydrogel promoted CAR-NK cell recruitment and tumor killing via sustained METTL3 inhibition. The hydrogel's Schiff base bonds further enabled intestinal adhesion and hemostasis in an incomplete tumor resection model of CRC. Combining the hydrogel with CAR-NK cell therapy significantly reduced CRC recurrence in vivo. Overall, our study reveals the crucial role of METTL3 in CRC recurrence and proposes a promising, multimodal strategy using STM2457-loaded hydrogel and CAR-NK cells for enhanced therapeutic efficacy.

研究领域: 肿瘤学 · 分子生物学 · 免疫疗法 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioengineering & Translational Medicine · 2023 · IF 7.4

Tissue adhesive indocyanine green-locking granular gel-mediated photothermal therapy combined with checkpoint inhibitor for preventing postsurgical recurrence and metastasis of colorectal cancer

Yuan Zeting,Ma Shuli,Li Yue,Fang Haowei,Shang Jing,Zhan Yueping,Wang Jie,Chen Teng,Deng Wanli,Kunxi Zhang,Yin Peihao

Developing effective therapy to inhibit postoperative recurrence and metastasis of colorectal cancer (CRC) is challenging and significant to reduce mortality and morbidity. Here, a granular hydrogel, assembled from gelatin microgels by dialdehyde starch and interpenetrated with in situ polymerized poly(sulfobetaine methacrylate- co -N-isopropylacrylamide) (P(SBMA- co -NIPAM)), is prepared to load and lock Food and Drug Administration (FDA)-approved indocyanine green (ICG) with definite photothermal function and biosafety for photothermal therapy (PTT) combining with checkpoint inhibitor. The presence of P(SBMA- co -NIPAM) endows granular hydrogel with high retention to water-soluble ICG, preventing easy diffusion and rapid scavenging of ICG. The ICG-locking granular hydrogel can be spread and adhered onto the surgery site at wet state in vivo, exerting a persistent and stable PTT effect. Combined with αPD-L1 treatment, ICG-locking granular hydrogel-mediated PTT can eradicate postsurgery residual and metastatic tumors, and prevent long-term tumor recurrence. Further mechanistic studies indicate that combination treatment effectively promotes dendritic cells maturation in lymph nodes, enhances the number and infiltration of CD8 + T and CD4 + T cells in tumor tissue, and improves memory T cell number in spleen, thus activating the antitumor immune response. Overall, ICG-locking gel-mediated PTT is expected to exhibit broad clinical applications in postoperative treatment of cancers, like CRC.

研究领域: 肿瘤学 · 生物材料科学 · 免疫学
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Advanced Science · 2024 ·Vol. 11 ·期 46 ·2309053 · IF 14.3

Protecting Against Postsurgery Oral Cancer Recurrence with an Implantable Hydrogel Vaccine for In Situ Photoimmunotherapy

Lan Chen,Qiqi Yin,Handan Zhang,Jie Zhang,Guizhu Yang,Lin Weng,Tao Liu,Chenghui Xu,Pengxin Xue,Jinchao Zhao,Han Zhang,Yanli Yao,Xin Chen,Shuyang Sun

Oral squamous cell carcinoma (OSCC) often recurs aggressively and metastasizes despite surgery and adjuvant therapy, driven by postoperative residual cancer cells near the primary tumor site. An implantable in situ vaccine hydrogel was designed to target residual OSCC cells post-tumor removal. This hydrogel serves as a reservoir for the sustained localized release of δ-aminolevulinic acid (δ-ALA), enhancing protoporphyrin IX-mediated photodynamic therapy (PDT), and a polydopamine-hyaluronic acid composite for photothermal therapy (PTT). Additionally, immune adjuvants, including anti-CD47 antibodies (aCD47) and CaCO 3 nanoparticles, are directly released into the resected tumor bed. This approach induces apoptosis of residual OSCC cells through sequential near-infrared irradiation, promoting calcium interference therapy (CIT). The hydrogel further stimulates immunogenic cell death (ICD), facilitating the polarization of tumor-associated macrophages from the M2 to the M1 phenotype. This facilitates phagocytosis, dendritic cell activation, robust antigen presentation, and cytotoxic T lymphocyte-mediated cytotoxicity. In murine OSCC models, the in situ vaccine effectively prevents local recurrence, inhibits orthotopic OSCC growth and pulmonary metastases, and provides long-term protective immunity against tumor rechalle nge. These findings support postoperative in situ vaccination with a biocompatible hydrogel implant as a promising strategy to minimize residual tumor burden and reduce recurrence risk after OSCC resection.

研究领域: 肿瘤学 · 免疫学 · 生物材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Polymer Materials · 2025 · IF 4.7

Doxorubicin-Loaded Injectable Hydrogel to Prevent Postoperative Recurrence of Colorectal Cancer and Accelerate Wound Healing

Chunyan Li,Linyin Xu,Yili Yin,Fengjiao Wei,Yanwei Hou,Yingyu Su,Jingya Zhao,Chenxu Lv,Tong Ren,Saifei Lv,Xue Yang,Lu Yue

Postoperative recurrence and impaired wound healing remain two critical challenges in colorectal cancer treatment. Local chemotherapy, as a promising strategy to address these issues, has attracted considerable attention. This study aimed to develop a sodium alginate (SA)-based injectable hydrogel encapsulating doxorubicin (DOX), with the dual goals of preventing postoperative colorectal cancer recurrence and promoting wound healing. The medicated hydrogel, termed DOX@OSAgel, enabled the sustained release of DOX, which effectively inhibited the proliferation of CT-26 cells and significantly suppressed tumor recurrence. Multiple lines of evidence strongly support this conclusion, including a marked reduction in tumor volumes, and a higher rate of tumor recurrence inhibition, and a substantial increase in apoptosis within CT-26 cells. Furthermore, Hematoxylin & Eosin (H&E) and Terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining assays further confirmed that DOX@OSAgel effectively suppressed postoperative recurrence of CT-26 tumors. Moreover, treatment with cargo-free OSAgel resulted in smaller wound sizes, accelerated wound closure, reduced inflammatory responses, and increased microangiogenesis, which indicated that the hydrogel accelerated wound healing. Collectively, DOX@OSAgel presents a promising local chemotherapeutic platform with the dual potential to inhibit postoperative recurrence and promote wound healing in colorectal cancer treatment.

CAS / MDL: 7664-93-9
研究领域: 肿瘤学 · 生物材料 · 药剂学 · 转化医学 · 分子肿瘤学 · 伤口修复 · 局部药物递送
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Delivery of NK cells in an injectable dynamic hydrogel effectively remodels tumor microenvironment and inhibits post-surgery tumor recurrence

Jiaying Long,Yicong Zhang,Mengxing Zhang,Zhenkang Diao,Taotian Zhang,Hanming Zhang,Qing Lin,Tao Gong,Xun Sun,Zhirong Zhang,Shiqi Huang,Ling Zhang

Adoptive immunotherapy against cancer based on natural killer (NK) cells has emerged as a promising strategy. However, the efficacy of NK cells in solid tumors is still unsatisfactory, where a major cause is the immune suppressive tumor microenvironment (TME) and limited delivery. Here, an injectable dynamic Schiff’s base hydrogel named SNgel was developed for growth and controlled delivery of NK cells to enhance the treatment of solid tumors. The hydrogel contains interleukin-15 and SCH-442416 nanoparticles coated with MnO 2 along with NK cells. After application, SNgel functions as a reservoir to continuously release NK cells and drugs, thereby improving the distribution and persistence of NK cells in vivo . Simultaneously‌, the platform can enhance the anti-tumor activity of NK cells by alleviating tumor hypoxia and blocking adenosine A2A receptors. As a result, SNgel effectively inhibited post-surgery recurrence of non-small cell lung cancer (NSCLC) with good safety profile. Thus, SNgel has good potential for further development and offers ground for designing other live cell-containing gel.

研究领域: 肿瘤学 · 免疫学 · 生物材料科学
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ADVANCED FUNCTIONAL MATERIALS · 2023 · IF 19

Immunotherapeutic Hydrogel with Photothermal Induced Immunogenic Cell Death and STING Activation for Post-Surgical Treatment

Meng Wang,Xiaohui Zhang,Bing Liu,Chen Liu,Caimei Song,Yu Chen,Yubei Jin,Jing Lin,Peng Huang,Shaojun Xing

Post-surgical tumor recurrence remains a major clinical concern for patients with malignant solid tumors. Herein, an immunotherapeutic hydrogel (SA PBA /ZMC/ICG) is developed by incorporating metal ion-cyclic dinucleotide (CDN) nanoparticles (Zn-Mn-CDN, ZMC) and a photosensitizer (indocyanine green, ICG) into phenylboronic acid (PBA)-conjugated sodium alginate (SA PBA ) for photothermal therapy (PTT)-triggered in situ vaccination to inhibit post-surgical recurrence and metastasis of malignant tumors. The gelation of SA PBA /ZMC/ICG in the residual tumors can achieve accurate local PTT and the local sustained release of CDN and Mn 2+ with minimal detrimental off-target toxic effects. Furthermore, CDN, which is an agonist of the stimulator of interferon genes (STING), along with Mn 2+ can activate the STING pathway and trigger type-I-IFN-driven immune responses against tumors. Therefore, the immunotherapeutic hydrogel with enhanced immune response by STING agonist and PTT-induced immunogenic cell death (ICD) reprograms the post-surgical immunosuppressive microenvironment, substantially decreasing the post-surgical recurrence and metastasis of solid tumors in multiple murine tumor models when administered during surgical resection. Taken together, PTT-triggered and STING-mediated in situ cancer vaccination is an effective therapeutic intervention for post-surgical recurrence and metastasis of tumors.

研究领域: 肿瘤学 · 免疫学 · 生物材料学
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ACS Biomaterials Science & Engineering · 2019 · IF 4.511

Graphene-Nanoparticle-Based Self-Healing Hydrogel in Preventing Postoperative Recurrence of Breast Cancer

Qiwen Li,Junru Wen,Chenlu Liu,Yanpeng Jia,Yongzhi Wu,Yue Shan,Zhiyong Qian,Jinfeng Liao

Hydrogel is an ideal scaffold in the fields of regenerative medicine and tumor therapy because of its biomimetic ability to modulate tissue microenvironment. Herein, we fabricated a new kind of self-healing hydrogel based on graphene nanoparticle and expanded its application in postoperative recurrence of breast cancer. First, a facile method was used to prepare self-healing hydrogel via Schiff-base linkage, which composed of chondroitin sulfate multialdehyde (CSMA), branched polyethylenimine (BPEI) and BPEI conjugated graphene (BPEI-GO). BPEI-GO was doped in the network and participated in Schiff-base reaction and stabilized the structure, as well as provided sustained drug delivery, and near-infrared laser (NIR)-triggered photothermal effect. The hydrogels exhibited excellent self-healing (∼100%) and improved mechanical properties (7,000 Pa). Further, in vitro breast cancer cell inhibition study showed enhanced cell killing efficiency with synergistic chemo-photothermal therapy. In the breast cancer postoperative recurrence prevention mice model, we found that combination of Doxorubicin (DOX) and photothermal therapy in CSMA/BPEI/BPEI-GO hydrogels group reduced tumor recurrence to 33.3%, compared with 66.7% for DOX-loaded hydrogels without NIR irradiation, 66.7% for local administration of free DOX, 100% for hydrogels with NIR irradiation, blank hydrogels, and blank control. This study suggests the great potential of CSMA/BPEI/BPEI-GO hydrogels for postoperative recurrence prevention of breast cancer.

研究领域: 生物医学工程 · 肿瘤学 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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Materials Science & Engineering C-Materials for Biological Applications · 2021 · IF 7.328

Injectable hydrogel loaded with paclitaxel and epirubicin to prevent postoperative recurrence and metastasis of breast cancer

QingQing Leng,Yue Li,Ping Zhou,Kang Xiong,Yun Lu,YongXia Cui,BiQiong Wang,ZhouXue Wu,Ling Zhao,ShaoZhi Fu

Post-operative recurrence and metastasis is a major challenge for breast cancer treatment. Local chemotherapy is a promising strategy that can overcome this problem. In this study, we synthesized an injectable hyaluronic acid (HA)-based hydrogel loaded with paclitaxel (PTX) nanoparticles and epirubicin (EPB) (PPNPs/ [email protected] ). PPNPs/ [email protected] steadily released the encapsulated drugs to achieve long-term inhibition of tumor recurrence and metastasis in a murine post-operative breast tumor model, which prolonged their survival without any systemic toxicity. The drug-loaded hydrogel inhibited the proliferation and migration of tumor cells in vitro , and significantly increased tumor cell apoptosis in vivo . Therefore, PPNPs/ [email protected] can be used as a local chemotherapeutic agent to prevent postoperative recurrence and metastasis of breast cancer.

CAS / MDL: 25952-53-8
研究领域: 肿瘤学 · 药学 · 生物医学工程
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BIOMATERIALS · 2022 · IF 15.304

Injectable adhesive hemostatic gel with tumor acidity neutralizer and neutrophil extracellular traps lyase for enhancing adoptive NK cell therapy prevents post-resection recurrence of hepatocellular carcinoma

Yusheng Cheng,Yihang Gong,Xiuxing Chen,Qi Zhang,Xijian Zhang,Yizhan He,Lijie Pan,Beibei Ni,Fan Yang,Yan Xu,Lei Zhou,Yang Yang,Wenjie Chen

Post-resection recurrence remains an intractable problem in hepatocellular carcinoma (HCC) management. Natural killer (NK) cell infusion is considered as a promising cancer therapy, but acidic tumor microenvironment (TME) and neutrophil extracellular traps (NETs) greatly counteract its efficacy. Recently, polymer hydrogels have aroused much interest in tumor combination therapy, since they load and controllably release therapeutic agents with high bioavailability and low systemic toxicity. Therefore, a biocompatible hydrogel with tumor acidity neutralizer and NETs lyase may show promise for enhancing NK infusion to prevent post-resection HCC recurrence. Herein, a dual pH-responsive hydrogel with tumor acidity neutralizer (mesoporous bioactive glass nanoparticles) and NETs lyase (Deoxyribonuclease I, DNase I) is developed and used in combination with NK cell infusion for preventing post-resection HCC recurrence. The hydrogel can be injected to surgical margin and form an adhesive gel with a rapid hemostasis . Besides, it neutralizes tumor acidity to reduce tumor infiltration of immunosuppressive cells, and releases DNase I in a pH-responsive manner to degrade NETs. Moreover, this combination therapy significantly enhances NK cell infusion to combat post-surgical HCC recurrence without systemic toxicity. This study provides proof of concept that combination of NK cell adoptive therapy and hydrogel-based delivery system can successfully prevent post-resection HCC recurrence.

研究领域: 肿瘤学 · 生物医学工程 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Asian Journal of Pharmaceutical Sciences · 2024 · IF 10.7

In Situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence

Shengnan Huang,Chenyang Zhou,Chengzhi Song,Xiali Zhu,Mingsan Miao,Chunming Li,Shaofeng Duan,Yurong Hu

Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO 2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn 2+ and produce O 2 , resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn 2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.

CAS / MDL: 50-99-7 14402-89-2
研究领域: 肿瘤学 · 生物材料学 · 免疫学
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