JOURNAL OF CONTROLLED RELEASE
·
2024
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IF 10.5
Shuang Zhu,Chenglu Gu,Long Gao,Shuanglong Du,Duiping Feng,Zhanjun Gu
Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate and limited treatment options. Concurrent chemoradiotherapy is considered beneficial to improve tumor control, but the low drug bioavailability at tumor site and the low radiation tolerance of surrounding healthy organs greatly limits its effectiveness. Lipiodol, a natural drug carrier used in clinical transarterial chemoembolization, has shown potential as a radiosensitizer due to its high Z element iodine composition. Thus, this study aims to repurpose lipiodol as a sensitizer to simultaneously enhance chemo- and radiotherapy for PDAC. To this end, a stable lipiodol emulsion (IOE) loaded with gemcitabine is designed using clinically approved surfactants. At in vivo level, IOE demonstrates better radiotherapeutic effect than existing nanoradiosensitizers and enhanced drug bioavailability over free drug, leading to significant tumor inhibition and improved survival rates under concurrent chemo-radiotherapy. This may due to the sustained drug release, homogenous spatial distribution, and long-term retention ability of IOE in solid PDAC tumor. Furthermore, to better understand the functioning mechanism of drug-loaded IOE, in vitro study is conducted to reveal the ROS- and DNA damage-related therapeutic pathways. Lastly, a comprehensive toxicity assessment also proves the good biocompatibility and safety of as-prepared IOE. This study offers a clinically feasible sensitizer for simultaneous chemoradiotherapy and holds potential for other types of cancer treatment in clinics.
研究领域:
肿瘤学
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放射治疗学
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药剂学
✓ 已验证
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Qixuan Dai,Lin Wang,Shilong Shao,Zhekun Jia,Syed Faheem Askari Rizvi,Xing Gao,Minglei Teng,Hu Chen,En Ren,Chengchao Chu,Gang Liu
The integration of local radiation therapy (RT) with transcatheter arterial chemoembolization (TACE) can effectively manage unresectable hepatocellular carcinoma (HCC). Nonetheless, achieving effective synergistic treatment efficacy by controlled on-dem, radiosensitization following TACE remains a significant issue. A nanoradiosensitizer-Lipiodol formulation (DSeSeP-API(Lip)) is developed using Touch-, -Go following X-ray irradiation (X-tag) for the theranostics of HCC. The nanoradiosensitizer (DSeSeP-API) is fabricated by conjugating ultrasmall AuPtICG (API) nanoparticles featuring an amphiphilic polymer with X-ray responsive diselenide motif (DSPE-Se-Se-PEG-SH), satisfying the ‘3 s ’ properties: 1) s table in Lipiodol; 2) s ensitive to X-ray; 3) phase- s hift from Lipiodol to the aqueous physiology. The homogeneous, stable lipiodol formulation is subsequently prepared via our super-stable homogeneous intermixed formulation technology (SHIFT). Following the successful transcatheter arterial embolization (TAE), the subsequent RT program commences. The initial X-ray irradiation is administered concurrently with the cleavage of the diselenide bond to facilitate the phase transition of hydrophilic SeP-API from Lipiodol ( 1 X-Tag). Secondary X-ray irradiation is applied at the peak cellular uptake of sensitizers for enhanced X-ray dynamic therapy (XDT) ( 2 X-ray). The research illustrates the capability of the nanoradiosensitizer-Lipiodol formulation with the “X-tag” feature to amplify the synergistic TAE−XDT therapeutic effects while effectively minimizing adverse effects.
研究领域:
肿瘤学
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放射医学
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介入治疗
✓ 已验证
产品关联
DOI
高影响因子
Theranostics
·
2022
·
IF 11.6
Pan He,En Ren,Biaoqi Chen,Hu Chen,Hongwei Cheng,Xing Gao,Xiaoliu Liang,Hao Liu,Jingdong Li,Bo Li,Aizheng Chen,Chengchao Chu,Xiaoyuan Chen,Jingsong Mao,Yang Zhang,Gang Liu
Background: Though lipiodol formulations are major options in transcatheter arterial chemoembolization (TACE) of advanced unresectable hepatocellular carcinoma (HCC) in the clinic, their application is severely limited by insufficient physical stability between the hydrophobic lipiodol and hydrophilic drugs; thus, most chemotherapeutic drugs are quickly released into systemic circulation resulting in poor therapeutic outcomes and serious side effects. Methods : The typical hydrophilic drug doxorubicin hydrochloride (DOX) was prepared as a pure nanomedicine and then stably and homogeneously dispersed in lipiodol (SHIFT&DOX) via slightly ultrasonic dispersion. The drug release profiles of SHIFT&DOX were defined in a decellularized liver model. In vivo therapeutic studies were performed in rat-bearing N1S1 orthotopic HCC models and rabbit-bearing VX2 orthotopic HCC models. Results : SHIFT&DOX features an ultrahigh homogeneous dispersibility over 21 days, which far surpassed typical Lipiodol-DOX formulations in clinical practice (less than 0.5 h). SHIFT&DOX also has excellent sustained drug release behavior to improve the local drug concentration dependence and increase the time dependence, leading to remarkable embolic and chemotherapeutic efficacy, and eminent safety in all of the orthotopic HCC models. Conclusions: The carrier-free hydrophilic drug nanoparticle technology-based lipiodol formulation provides a promising approach to solve the problem of drug dispersion in TACE with the potential for a translational pipeline.
研究领域:
肿瘤学
·
药剂学
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介入放射学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yue Yu,Yang Liu,Chao Wang,Chang Chen,Qingsong Ye,Zhewei Zhang,Lifeng Luo,Chengjun Song,Chenxuan Zhao,Zhiwen Zou,Yitao Ding,Jinhui Wu
Tumor embolization therapy often involves complex procedures and poses challenges for physicians, especially with radiological imaging guidance. Inspired by physiological processes of misfolded protein aggregation and thrombus formation, we developed a protein-based embolic agent using ethiodized oil and human serum albumin for targeted tumor embolization. By occupying the hydrophobic cavity of albumin and disrupting its refolding process, these ethiodized oil bound human serum albumin nanoparticles (Oil@HSA NPs) achieve spontaneous aggregation and size growth at high concentrations, a unique advantage over conventional phospholipid nanoparticles. When combined with bacterium-induced coagulation in tumor vessels, Oil@HSA NPs selectively accumulate at tumor sites, blocking blood flow and significantly inhibiting tumor growth. This study introduces a practical and innovative approach to tumor embolization, offering a streamlined and effective alternative for vascular targeting in cancer therapy.
研究领域:
医学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Hu Chen,Hongwei Cheng,Qixuan Dai,Yi Cheng,Yang Zhang,Dengfeng Li,Yang Sun,Jingsong Mao,Ke Ren,Chengchao Chu,Gang Liu
Accurate identification of surgical margins for malignancy remains a challenge in the surgical therapy of cancer, and this encountered interoperative difficulties which directly contribute to the prognosis of patients. In recent years, indocyanine green (ICG) has been approved and applied in clinical settings for lesions detection, especially for the precise surgical resection. However, rapid clearance and poor stability greatly limit its clinical practicality. Herein, a super-stable homogeneous iodinated formulation technology (SHIFT) is designed to realize sufficient dispersion of ICG into lipiodol (SHIFTs) for transcatheter embolization (TAE) synergistic fluorescence-guided resection. Particularly, SHIFTs is prepared in a green physical mixture via a carrier-free manner, which possesses controlled morphology, long-term stability, and improved optical characteristics of ICG (fluorescence/photoacoustic/photothermal activities). Furthermore, the viscosity of the synthetic solvent is comparable to lipiodol, and further assessment demonstrated the same efficacy in computed tomography . The performance of SHIFTs in the fluorescence navigation was further evaluated in vivo by TAE therapy to the rabbit VX2 tumor model for a two-week monitor. The integration of near-infrared fluorescence surgery navigation and TAE could effectively guarantee the precise resection for hepatocellular carcinoma . This SHIFT system provides good potentials for ameliorating the dilemma of precise fluorescent navigation for surgical resection after arterial embolization in clinical practice.
研究领域:
医学影像学
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肿瘤学
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外科手术
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Yingao Ma,Jingyu Xiao,Gina Jinna Chen,Hong Dang,Yaran Zhang,Xiaoqin He,Perry Ping Shum,Qiongyu Guo
Photothermal treatment has garnered immense interest as a promising approach for biomedical applications such as cancer ablation, yet its effectiveness is often limited by insufficient laser penetration and challenges in achieving efficient targeting of photothermal agents. Here we developed a transvascular interventional photothermal therapy (Ti-PTT), which employed a small-sized microcatheter (outer diameter: 0.63 mm, 1.9 Fr) equipped with an ultrafine optical fiber (diameter: 100 m) capable of simultaneously delivering photothermal agents while performing 808 nm laser irradiation via an endovascular route. Specifically, we employed two types of indocyanine green (ICG)-based photothermal agent, i.e. ICG solution serving as purely photothermal agent and ICG-ethiodized oil (ICG-EO) emulsion acting as radiopaque photothermal embolic agent. Using the customized microcatheter with the ICG solution, both proximal and distal embolization were able to executed in a rat liver model. Compared to the ICG solution, the ICG-EO emulsion dramatically enhanced the ICG retention time, enabling photothermally triggered precision vascular blockade to induce local embolization of large tissue volumes in a rat kidney model with unfavored ICG leakage rate. The Ti-PTT paves a way to broaden the potential applications of photothermal therapy through combining with clinical intervention-based approaches.
研究领域:
生物医学工程
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诊疗学
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癌症治疗
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介入放射学
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光热科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Xing Gao,Hongwei Cheng,Minglei Teng,Hongrui Zhang,Hu Chen,Songnan Qu,Gang Liu
Transcatheter arterial chemoembolization (TACE) is the principal treatment option for patients with unresectable hepatocellular carcinoma (HCC). However, the hypoxic microenvironment following TACE can promote angiogenesis and suppress tumor ferroptosis, resulting in an unfavorable prognosis. Tirapazamine (TPZ), a hypoxia-activated prodrug with specific cytotoxicity for hypoxic cells, making it a potential candidate for TACE. To develop an effective hypoxia-responsive drug delivery platform for TACE, we propose a novel lipiodol embolic formulation that integrates TPZ and sorafenib (SFB) by super-stable homogeneous intermixed formulation technology (SHIFT). This approach achieves the manufacture of embolic agents with stable drug dispersion characteristics, fulfilling the need for sustained drug release in TACE. The prolonged tumor penetration of TPZ exhibited embolization-responsive tumor killing, and its combination with SFB can suppress hypoxia-induced angiogenesis and trigger tumor ferroptosis, maintaining low oxygen levels, thereby boosting the therapeutic efficacy of TPZ. Conversely, TPZ can combat the resistance to SFB in hypoxic tumor cells. In summary, this study developed a novel embolization drug formulation based on embolic hypoxic microenvironment. The synergistic mechanism of TPZ and SFB enhances the therapeutic effects of hypoxia-activated prodrugs and mitigates the adverse effects of hypoxia.
研究领域:
肿瘤学
·
药理学
·
介入放射学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Kanghua Zeng,Bohong Chen,Qifan Liu,Zheng Zhou,Xiahong Xie,Xiangna Zhang,Xiang Li,Xiuping Zhang,Ben Ma,Mingzhou Ye
Intra-abdominal hemorrhage is a life-threatening condition with high mortality. Rapid localization of the bleeding point is crucial. Conventional computed tomography (CT) imaging is limited by the rapid diffusion and poor retention of small-molecule iodine agents, restricting sensitivity and imaging duration. To overcome these challenges, an “AB-type” hydrogel CT contrast system is developed based on bio-orthogonal click chemistry, designed to enhance both detection sensitivity and spatial precision. The system consists of iodized oil-loaded liposomal nanoparticles (INb NPs) administered intravenously and tetrazine-functionalized hyaluronic acid (HA-Tz) delivered intraperitoneally. At the bleeding site, the two components undergo a rapid click reaction, forming an in situ hydrogel that anchors the contrast agent for prolonged retention and precise localization. This approach demonstrated efficient gelation in vitro and robust performance in vivo, significantly extending the imaging window and sensitivity compared with Iohexol. HA-Tz@INb NPs enhance CT signal intensity and imaging duration by over 60 fold, enabling sensitive detection of occult bleeding. The hydrogel exhibits excellent biosafety, being removable by lavage and fully degradable within days without adverse effects. By integrating nanotechnology, click chemistry, and hydrogel engineering, this strategy provides a clinically translatable diagnostic platform with superior precision and sensitivity for intra-abdominal bleeding.
研究领域:
纳米医学
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生物医学成像
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急诊医学
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生物材料
·
分子诊断
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Jiayao Chen,Jiani Liu,Duo Xu,Junfeng Liu,Xiaojun Chen,Shuai Yang,Pan Yin,Zebo Jiang,Chaoming Mei,Xiaoting Zhang,Lizhu Wang,Ke Zhang,Bin Zhou,Hong Shan,Dan Li,Pengfei Pang
Transcatheter arterial chemoembolization (TACE), the mainstream treatment for hepatocellular carcinoma (HCC), is a method of blocking tumor blood vessels with a mixture of lipiodol and chemotherapeutics. And the contrast-enhanced computed tomography (CT) is the commonly used way for follow-up of HCC after TACE. However, it is noteworthy that when lipiodol deposition plays an embolic effect, it also produces high-density artifacts in CT images. These artifacts usually conceal the enhancement effect of iodine contrast agents. As a result, the residual region is difficult to be visualized. To overcome this obstacle, we developed one kind of Lu 3+ /Gd 3+ doped fluoride nanoprobe modified with Dp-PEG2000 to realize CT/MRI dual-modality imaging of HCC. Compared with lipiodol or ioversol , the obtained PEGylated product LG-PEG demonstrated a greater density value in high keV CT images. In vitro experiments showed the lipiodol artifacts can be removed in virtual non-contrast (VNC) imaging, but the density of ioversol was also removed at the same time. However, the LG-PEG synthesized in this work can still maintain a high density in VNC imaging, which indicates that LG-PEG can exploit its advantages to the full in VNC imaging. Furthermore, LG-PEG successfully exerted tumor enhancement effects in the in vivo VNC images of HCC with lipiodol deposition. In addition, LG-PEG exhibited a strong T 2 enhancement effect with low biological toxicity and less side-effect on the main organ and blood. Thus, the LG-PEG reported in this research can serve as an effective and safe VNC contrast agent for HCC imaging after TACE.
研究领域:
医学成像
·
纳米技术
·
肿瘤学
·
放射学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）