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JOURNAL OF NANOBIOTECHNOLOGY · 2025 ·Vol. 23 ·期 1 ·1-21 · IF 12.6

A lyophilizable LNP vaccine enables STING-reinforced postoperational adjuvant immunotherapy

Yang Yi,Guo Jiaxin,Qi Jialong,Deng Wenxia,Hu Jialin,Hasan Muhammad Waqqas,Deng Fei,Zhou You,Song Zhengji,Deng Wei,Chen Wenjie

Immune checkpoint blockade therapy (iCBT) has revolutionized cancer treatment, however, there is a low response rate, especially in treating postsurgical reoccurring tumors. Vaccine based immunotherapy can sensitize iCBT, but its development was largely hindered by inefficient delivery and high requirements of storage. In this study, the vaccine loaded with immunostimulant was employed to improve iCBT-based adjuvant postsurgical therapy. A lyophilized, antigen E7 peptide and manganese ion (Mn 2+ ) co-delivered tumor vaccine was developed based on lipid nanoparticles (EM@LNP). The vaccination efficacy was examined in both prophylactic and therapeutic schemes in murine subcutaneous models, the synergetic effect of vaccination combined with anti-PD-1 therapy was further investigated in post-operative tumor model. EM@LNP vaccination elicited effective CD8 + T cell response through modulating tumor immunosuppressive microenvironment and conferring immune memory, demonstrating potent immunization in both preventive and therapeutic schemes. What’s more, EM@LNP vaccination orchestrated with iCBT, efficiently repressing tumor recurrence. Further mechanism studies using inhibitor for cells invitro and the investigation using STING −/− mice confirmed that the cGAS-STING signaling pathway activated by Mn 2+ is indispensable for LNP vaccination and the coordination with iCBT-based adjuvant immunotherapy. In summary, this study shows a lyophilized LNP vaccine could significantly amplify iCBT efficiency, providing a translational strategy of adjuvant immunotherapy for treating postsurgical tumor recurrence. Graphical abstract

CAS / MDL: 6156-78-1
研究领域: 肿瘤学 · 免疫学 · 药剂学 · 生物医学工程
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Scientific Reports · 2016 ·Vol. 6 ·期 1 ·1-10 · IF 5.228

Antinociceptive effects of vitexin in a mouse model of postoperative pain

Zhu Qing,Mao Li-Na,Liu Cheng-Peng,Sun Yue-Hua,Jiang Bo,Zhang Wei,Li Jun-Xu

Vitexin, a C-glycosylated flavone present in several medicinal herbs, has showed various pharmacological activities including antinociception. The present study investigated the antinociceptive effects of vitexin in a mouse model of postoperative pain. This model was prepared by making a surgical incision on the right hindpaw and von Frey filament test was used to assess mechanical hyperalgesia. Isobolographical analysis method was used to examine the interaction between vitexin and acetaminophen. A reliable mechanical hyperalgesia was observed at 2 h post-surgery and lasted for 4 days. Acute vitexin administration (3–10 mg/kg, i.p.) dose-dependently relieved this hyperalgesia, which was also observed from 1 to 3 days post-surgery during repeated daily treatment. However, repeated vitexin administration prior to surgery had no preventive value. The 10 mg/kg vitexin-induced antinociception was blocked by the opioid receptor antagonist naltrexone or the GABA A receptor antagonist bicuculline. The doses of vitexin used did not significantly suppress the locomotor activity. In addition, the combination of vitexin and acetaminophen produced an infra-additive effect in postoperative pain. Together, though vitexin-acetaminophen combination may not be useful for treating postoperative pain, vitexin exerts behaviorally-specific antinociception against postoperative pain mediated through opioid receptors and GABA A receptors, suggesting that vitexin may be useful for the control of postoperative pain.

研究领域: 药理学 · 疼痛研究 · 神经科学
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MACROMOLECULAR BIOSCIENCE · 2024 · IF 4.4

In Situ Forming Injectable Gelatin-Based Antibacterial Bioadhesives for Preventing Postoperative Leakage and Abdominal Adhesions

Shibo Hu,Wanglin Duan,Xianzhen Jin,Chaowei Li,Bin Zhu,Yurong Chen,Ye Zhu,Peihai Cao,Zepeng Dong,Luyao Feng,Junhui Yu,Xuejun Sun,Zeshaan Yahaya Haji Mahmood,Yazhong Bu,Baoji Du,Jianbao Zheng

Postoperative anastomotic leakage (AL) and abdominal adhesions are two major complications after intestinal surgery, with an incidence of 2–25% for AL and 93% for adhesion. Until now, there is no method addressing AL and abdominal adhesions simultaneously. In this work, Bi-PEG–succinimidyl succinate (PEG-NHS), amino-gelatin (Agel) is combined with cefoperazone-sulbactam (SCF) to prepare a multifunctional bioadhesive (SCF/SEAgel) for the postoperative leakage and adhesion prevention. SCF/SEAgel possesses a great sealing capability for tissue, with a bursting pressure of 54 kPa. The loaded SCF endows the systems with good antibacterial properties. The in vivo antiadhesion experiments show that SCF/SEAgel possesses better anti-adhesion properties than the commercially used sodium hyaluronate gel. In the cecum leakage model, the SCF/SEAgel effectively seals the leakage with a survival rate of 100%, superior to commercial products (Sainaoning). Meanwhile, it significantly reduces tissue adhesion. Finally, the laparoscopic surgery with dogs shows that the SCF/SEAgel can be injected through minimally invasive surgery, demonstrating its ease of use. Combined with its great biocompatibility, SCF/SEAgel is very promising in intestinal surgery.

CAS / MDL: 6066-82-6 25322-68-3
研究领域: 生物医学材料 · 外科手术 · 药剂学
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Advanced Science · 2018 ·Vol. 5 ·期 5 ·1700848 · IF 12.441

Black-Phosphorus-Incorporated Hydrogel as a Sprayable and Biodegradable Photothermal Platform for Postsurgical Treatment of Cancer

Jundong Shao,Changshun Ruan,Hanhan Xie,Zhibin Li,Huaiyu Wang,Paul K. Chu,Xue-Feng Yu

Photothermal therapy (PTT) is a fledgling therapeutic strategy for cancer treatment with minimal invasiveness but clinical adoption has been stifled by concerns such as insufficient biodegradability of the PTT agents and lack of an efficient delivery system. Here, black phosphorus (BP) nanosheets are incorporated with a thermosensitive hydrogel [poly( d , l -lactide)-poly(ethylene glycol)-poly( d , l -lactide) (PDLLA-PEG-PDLLA: PLEL)] to produce a new PTT system for postoperative treatment of cancer. The BP@PLEL hydrogel exhibits excellent near infrared (NIR) photothermal performance and a rapid NIR-induced sol–gel transition as well as good biodegradability and biocompatibility in vitro and in vivo. Based on these merits, an in vivo PTT postoperative treatment strategy is established. Under NIR irradiation, the sprayed BP@PLEL hydrogel enables rapid gelation forming a gelled membrane on wounds and offers high PTT efficacy to eliminate residual tumor tissues after tumor removal surgery. Furthermore, the good photothermal antibacterial performance prevents infection and this efficient and biodegradable PTT system is very promising in postoperative treatment of cancer.

研究领域: 医学 · 材料科学 · 肿瘤学
✓ 已验证 DOI PubMed 高影响因子
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ACS Nano · 2023 · IF 17.1

Nanocrystals Slow-Releasing Ropivacaine and Doxorubicin to Synergistically Suppress Tumor Recurrence and Relieve Postoperative Pain

Fei Peng,Jing Liu,Junjie Chen,Weiwei Wu,Yujun Zhang,Guoyan Zhao,Yi Kang,Deying Gong,Liu He,Jing Wang,Wensheng Zhang,Feng Qiu

Although surgical resection provides a straightforward and effective treatment for most malignant solid tumors, tumor recurrence and acute postoperative pain continue to be two big problems associated with this treatment. To resolve these problems, a nanocrystal composite slow-releasing ropivacaine and doxorubicin was fabricated in this study. Briefly, a self-assembling peptide was used to form nanoparticle complexes with the two drugs, based on which homogeneous nanocrystals were obtained by adjusting the pH. In cultured human melanoma cells, the nanocrystals exhibited improved antitumor activity due to a synergistic effect and enhanced cellular uptake of the two drugs. On the other hand, the nanocrystals could slowly release ropivacaine in vitro and in vivo, generating long-acting analgesia on the rat sciatic nerve block model and incisional pain model. On a nude mouse tumor resection model, the nanocrystals simultaneously suppressed the recurrence of solid tumor and relieved postoperative pain, indicating a potential postoperative treatment for tumor resection patients. This nanocrystal system also suggested a promising and facile strategy for developing multifunctional formulations combining different drugs, which could achieve better therapeutic outcomes in a synergistic and sustained manner.

CAS / MDL: 94-75-7 7440-16-6
研究领域: 药剂学 · 肿瘤学 · 疼痛管理
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Facile Preparation of Drug-Releasing Supramolecular Hydrogel for Preventing Postoperative Peritoneal Adhesion

Xianwen Song,Zequn Zhang,Zhaolong Shen,Jun Zheng,Xi Liu,Yaqiong Ni,Jun Quan,Xiaorong Li,Gui Hu,Yi Zhang

Hydrogels have attracted widespread attention for breaking the bottlenecks faced during facile drug delivery. To date, the preparation of jelly carriers for hydrophobic drugs remains challenging. In this study, by evaporating ethanol to drive the formation of hydrogen bonds, hydrophilic poly(vinyl alcohol) (PVA) and certain hydrophobic compounds [luteolin (LUT), quercetin (QUE), and myricetin (MYR)] were rapidly prepared into supramolecular hydrogel within 10 min. The gelation performance of these three hydrogels changed regularly with the changing sequence of LUT, QUE, and MYR. An investigation of the gelation pathway of these hybrid gels reveals that the formation of this type of gel follows a simple supramolecular self-assembly process, called “hydrophobe–hydrophile crosslinked gelation”. Because the hydrogen bond between PVA and the drug is noncovalent and reversible, the hydrogel has good plasticity and self-healing properties, while the drugs can be controllably released by tuning the output stimuli. Using a rat sidewall-cecum abrasion adhesion model, the as-prepared hydrogel was highly efficient and safe in preventing postsurgical adhesion. This work provides a useful archetypical template for researchers interested in the efficient delivery and controllable release of hydrophobic drugs.

研究领域: 生物材料学 · 药剂学 · 医学
✓ 已验证 DOI PubMed 高影响因子
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Biomedical Engineering Online · 2024 ·Vol. 23 ·期 1 ·1-10 · IF 2.9

Expression of periostin in the epithelium of cholesteatoma with different degrees of ossicular chain destruction and its clinical value in predicting postoperative hearing recovery

Xie Cuncun,Jia Xiaodong,Ding Shaoguang,Ding Xiaoli,Wang Guangke,Liu Hongjian

Objectives To explore the expression of periostin in the epithelium of cholesteatoma with different destruction degrees of the ossicular chain and its clinical value in predicting postoperative hearing recovery. Methods Retrospective analysis was conducted on the clinical data of 100 patients with middle ear cholesteatoma (the cholesteatoma group) admitted to our hospital. Another 100 patients without middle ear cholesteatoma treated in our hospital during the same period were included in the non-cholesteatoma group. Middle ear cholesteatoma patients were further divided into a normal group, a partial destruction group, and a complete destruction group based on the destruction degree of the ossicular chain (Maresh grading). After the treatment, 75 cases were considered as the effective group and 25 cases as the ineffective group. The expression of tumor necrosis factor-alpha, Interleukin 6, and periostin in the epithelium of middle ear cholesteatoma patients with different destruction degrees of the ossicular chain and different therapeutic effects were compared. The correlation between periostin and inflammatory factors was analyzed using Pearson analysis. The predictive value of tumor necrosis factor-alpha, Interleukin 6, and periostin on treatment effect was valued using the receiver operating characteristic curve. Results Patients in the cholesteatoma group had a much higher content of tumor necrosis factor-alpha, Interleukin 6, and periostin than those in the non-cholesteatoma group ( P  < 0.001). The expression of tumor necrosis factor-alpha, Interleukin 6, and periostin was also largely increased with the destruction group of the ossicular chain. Patients in the ineffective group had much higher expression of tumor necrosis factor-alpha, Interleukin 6, and periostin than those in the effective group ( P  < 0.001). The Pearson correlation analysis results showed that periostin was positively correlated with the content of tumor necrosis factor-alpha and interleukin 6 ( P  = 0.868, 0.880, P  < 0.001). The areas under the curve of individual or joint tumor necrosis factor-alpha, Interleukin 6, and periostin were 0.627, 0.793, 0.822, and 0.892, respectively. Conclusions The expressions of periostin, Interleukin 6, and tumor necrosis factor-alpha were markedly increased in the epithelium of middle ear cholesteatoma patients, which were gradually increased with the aggravation of the ossicular chain destruction. Periostin, Interleukin 6, and tumor necrosis factor-alpha could be used as important indicators to predict postoperative hearing recovery.

CAS / MDL: 7558-80-7 24937-79-9
研究领域: 耳科学 · 分子生物学 · 临床医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Science China-Materials · 2024 ·Vol. 67 ·期 5 ·1521-1532 · IF 6.8

Injectable and self-fused hydrogels with antifouling capability based on amino acid derivatives for postoperative anti-adhesion application

Li Meng,Zhang Mengyuan,Liu Zheng,Xie Ruilin,Yang Yuxuan,Shen Kaixiang,Yang Aimin,Cheng Yilong

The design and fabrication of injectable barriers with promising antifouling capability to prevent the formation of adhesions after surgery remains challenging. Herein, we introduce amino acid derivative with hydroxyl group ( N -acryloyl serine (ASer)) into the preparation of hydrogels to develop a novel hydrogen bond-crosslinked hydrogel (PASer) by free radical polymerization. It is found that one substituted methyl group can cause considerable disruption to the hydrogen bonding interaction and result in increased initial gelling concentration and significant decrease in the mechanical properties of poly( N -acryloyl threonine) (PAThr) hydrogel compared with PASer hydrogel. Moreover, it is worth noting that the hydrophilic hydroxyl groups enable PASer hydrogel to efficiently resist protein adsorption and cell adhesion. The PASer hydrogel possesses excellent mechanical performance, injectability, self-fusion, good biocompatibility and appropriate in vivo residence time, which are consistent with the requirements of postoperative anti-adhesion materials in clinical practice. In vivo studies reveal that the advanced hydrogel shows satisfactory preventive effect on postoperative peritoneal adhesions in the established mice abdominal wall defect model.

CAS / MDL: 7727-54-0
研究领域: 生物材料学 · 医学工程 · 组织工程
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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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JOURNAL OF CONTROLLED RELEASE · 2022 · IF 11.467

Sequentially sustained release of anticarcinogens for postsurgical chemoimmunotherapy

Qian Chen,Yanan Li,Shuai Zhou,Dali Chen,Muye Zhou,Qinying Chen,Yuren Lu,Naicong Cai,Can Liu,Yumeng Guo,Zijie Qiu,Xiaoyan Hou,Jiasheng Tu,Weiyang Shen,Chunmeng Sun

Postsurgical treatment is of great importance to combat tumor recurrence and metastasis. Anti-CD47 antibodies (aCD47) can block the CD47-signal regulatory protein-alpha (CD47-SIRPα) pathway to restore immunity. Here, an in-situ gel implantation was engineered by crosslinking chitosan (CS) and pullulan (Pul) for postsurgical treatment. A highly selected chemotherapeutic, cyclopamine (Cyc), encapsulated in liposomes (Cyc-Lip) was co-loaded with aCD47 in gels for chemoimmunotherapy. Importantly, a sequential drug release kinetics can be achieved. Nanotherapeutics were confirmed to be released prior to aCD47 in a burst-release manner, which was benefit for immediately killing residual tumor cells followed by releasing tumor antigens . Meanwhile, aCD47 was released in a sustained-release manner to restore macrophage functions and exert anti-tumor immune responses. Afterwards, the efficacy of in-situ chemoimmunotherapy was confirmed on 4T1 mouse breast cancer models, which could not only efficiently augment anti-tumor effect to inhibit tumor recurrence but also establish a long-term immune memory to combat tumor metastasis.

研究领域: 肿瘤学 · 生物材料学 · 免疫学
✓ 已验证 DOI PubMed 高影响因子
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Acta Biomaterialia · 2025 · IF 9.6

An Injectable in Situ Gel Formed by Ropivacaine with Small Lipid Molecules to Achieve Long-term Postoperative Analgesia

YiQing Shen,Xin Tan,Lin Zhou,ZiHan Sun,Min Han,Min liang,DongHang Xu

Although local anesthetics (LA) are non-addictive and effective in managing postoperative pain, their short-term effects limit their clinical utility. In this study, we constructed an in situ gel injection formulation with stearic acid-ropivacaine hydrophobic ion-pair (HIP) and glycerol monoglyceride (SA-ROP-GMS) for multiday postoperative pain management. As an in situ gel, SA-ROP-GMS avoids the burst release effect common to water-soluble small molecule drugs in liposomes and hydrogels. Meanwhile, the hydrophobic ion-pair formed by ropivacaine and stearic acid contributes to the gel's stabilization and slow-release properties. In vivo evaluation of mouse models of pain demonstrated that the formulation provided multiday analgesia. And the absence of systemic toxicity of SA-ROP-GMS was verified by histological and blood biochemical studies. This study demonstrated the safety and efficacy of an injectable ropivacaine formulation based on in situ gel. The materials used in SA-ROP-GMS are safe and easy to obtain, and the preparation process is simple and fast, providing a convenient and effective strategy for the development of single-dose long-acting local anesthetic products, which is of great significance for postoperative pain management. Statement of Significance More than 80% of patients experience severe postoperative pain, and poor pain control reduces recovery satisfaction while increasing the risk of chronic pain. In this study, we constructed an injectable in situ gel using all-small-molecule excipients for slow-release drug delivery for the first time. We designed a method to form a lipid drug coupling between ropivacaine and stearic acid (SA-ROP HIP), which was then combined with glyceryl monostearate (SA-ROP-GMS). SA-ROP-GMS maintained analgesia for nearly 10 days in a single dose, significantly improving ease of administration and patient compliance. In addition, the auxiliary ingredients used in this study are biocompatible and inexpensive. This formulation follows the trend of regional anesthesia and provides a new solution for postoperative pain management.

研究领域: 药剂学 · 疼痛管理 · 生物材料
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2025 · IF 8.1

Enhanced Prevention on Postoperative Atrial Fibrillation by Using Anti-inflammatory Biodegradable Drug Patch

Yu Pengcheng,Lu Weiqi,Sun Huaxin,Huang Chengchen,Zhou Xiaolin,Wang Yuxing,Zhang Zhen,Fu Guosheng,Liu Hanxiong,Ren Kefeng,Sheng Xia

Postoperative atrial fibrillation (POAF) is the most prevalent form of secondary atrial fibrillation and increase the risk of adverse cardiovascular outcomes, such as stroke, heart failure, and increased mortality. Herein, we designed an andrographolide (Andr)-loaded degradable polymer patch to deliver the drug directly to the atrial tissue for prevention of POAF. The sterile pericarditis (SP) rat model was adopted for highly relationship to clinical practice. The patch-released Andr effectively reduced the incidence of atrial fibrillation from 90% to 20%, and alleviated local atrial inflammation and oxidative stress in vivo, by using electrophysiological detection and histological analysis such as immunofluorescence, western blot, PCR and so on. In HL-1 cells, we found the use of Andr-loaded patch could strongly inhibited the cell death, reactive oxygen species (ROS) generation and mitochondrial injury caused by LPS. Meanwhile, the use of Andr-loaded patch could effectively inhibited macrophages polarize towards M1. Mechanistically, we verified that the regulation of the cytoplasm and mitochondria Ca2+ and ROS dynamic balance was quite important both in vivo and in vitro. Our strategy proved by regulating the inflammatory microenvironment, ROS balance and Ca2+ homeostasis, and the Andr-loaded atrial patch was effective for POAF in the SP rat model. The electrical signal of atrial stromal reentry in the case of this model was successfully mined, and the results of calcium channel were basically consistent with that of electrical signal channel. In addition, we have reported the infiltration and polarization of local inflammatory cells in the atrial of POAF at the tissue section level. Our study served as a new inspiration for the treatment of arrhythmic diseases and other ROS- and Ca2+- associated local illnesses.

CAS / MDL: 106797-53-9 150-76-5
研究领域: 心血管医学 · 药理学 · 生物医学工程
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