INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
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IF 4.784
Guobao Chen,Runan Wei,Xiang Huang,Fuping Wang,Zhongmin Chen
Transcatheter arterial chemoembolization (TACE) is well known as an effective treatment for hepatocellular carcinoma (HCC). In the present study, a novel embolic agent of sodium alginate (SA)-modified silk fibroin (SF) microspheres was successfully prepared by emulsifying cross-linking method. The SA-modified SF microspheres were evaluated for the ability of embolization by investigating the morphology, particle size, swelling ratio, degradation, cytotoxicity, blood compatibility, and in vivo embolization. The results found that SA-modified SF microspheres had smooth surfaces and good sphericity. Swelling ratio of the microspheres can meet the requirements of arterial embolic agent and have pH and temperature sensitivity. Furthermore, hemolytic and anticoagulant studies have proved that the microspheres have good blood compatibility. Cytotoxicity tests indicated that the microspheres could promote the proliferation of fibroblasts and HUVEC. In vivo embolization evaluation of microspheres revealed that the arteries could be embolized by SA-modified SF microspheres in 3 weeks. The ability of drug loading and releasing of microspheres was proved by the controlled release profile of Adriamycin hydrochloride. The findings indicated that the SA-modified SF microspheres can be used as a potentially biodegradable arterial embolic agent for liver cancer therapy.
研究领域:
生物医学工程
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药学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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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
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药理学
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介入放射学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Menghui Liu,Yang Sun,Yitong Zhou,Yanlv Chen,Meng Yu,Liujun Li,Leye Yan,Yajun Yuan,Jiayao Chen,Kaixiang Zhou,Hong Shan,Xin Peng
Transcatheter arterial chemoembolization (TACE) has proven effective in blocking tumor-supplied arteries and delivering localized chemotherapeutic treatment to combat tumors. However, traditional embolic TACE agents exhibit certain limitations, including insufficient chemotherapeutic drug-loading and sustained-release capabilities, non-biodegradability, susceptibility to aggregation, and unstable mechanical properties. This study introduces a novel approach to address these shortcomings by utilizing a complex coacervate as a liquid embolic agent for tumor chemoembolization. By mixing oppositely charged quaternized chitosan (QCS) and gum arabic (GA), a QCS/GA polymer complex coacervate with shear-thinning property is obtained. Furthermore, the incorporation of the contrast agent Iohexol (I) and the chemotherapeutic doxorubicin (DOX) into the coacervate leads to the development of an X-ray-opaque QCS/GA/I/DOX coacervate embolic agent capable of carrying drugs. This innovative formulation effectively embolizes the renal arteries without recanalization. More importantly, the QCS/GA/I/DOX coacervate can successfully embolize the supplying arteries of the VX2 tumors in rabbit ear and liver. Coacervates can locally release DOX to enhance its therapeutic effects, resulting in excellent antitumor efficacy. This coacervate embolic agent exhibits substantial potential for tumor chemoembolization due to its shear-thinning performance, excellent drug-loading and sustained-release capabilities, good biocompatibility, thrombogenicity, biodegradability, safe and effective embolic performance, and user-friendly application.
研究领域:
肿瘤学
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2023
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IF 5
Xinmeng Shi,Ye Xietao,Linqing Huang,Liangyin Wei,Chen Miaoying,Ding Qu,Congyan Liu,Qin Chen,Yuping Liu,Yan Chen
Transcatheter arterial chemoembolization (TACE) is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply. Blood-vessel-embolic agents play key role on TACE. In the present work, we reported a Bletilla striata polysaccharide/poly (N-isopropylacrylamide) (BSP/PNIPAM) thermosensitive microemulsion gel loaded with magnetic icaritin (ICT) microemulsion (IS-MEs) as embolic agent (ISBP) for the first time. IS-MEs co-loaded with ICT and superparamagnetic iron oxide nanoparticles (SPIONs) were prepared by water titration method. The particle size of IS-MEs was 27.97 ± 0.25 nm, encapsulation efficiency was 97.18%, and presented a regular sphere under TEM. BSP/PNIPAM was prepared by free radical polymerization, which has good biocompatibility, excellent procoagulant function and dense microstructure. The lower critical solution temperature (LCST) of ISBP was 30 °C, which had excellent in vitro injection performance. The microscopic morphology of ISBP was loose and porous, the long-acting sustained-release time could reach 144 h, and the maximum ICT release was (48.6 ± 8.5) %. IPSBs with SPIONs exhibit desirable imaging properties and macrophage M1 polarization function. During the rabbit renal artery embolization, ISBP showed excellent distal vascular embolization performance and there was no obstruction or adhesion of the catheter. These results suggest that a novel in situ multifunctional traditional Chinese medicine thermosensitive microemulsion gel embolic agent has been developed with a potential application as a liquid embolic solution for TACE.
研究领域:
介入放射学
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药学
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纳米技术
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传统中药
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癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
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2024
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IF 15.8
Yutao Ma,Zhihua Li,Yucheng Luo,Yao Chen,Le Ma,Xiaoya Liu,Jingyu Xiao,Man Huang,Yingnan Li,Hongliang Jiang,Meijuan Wang,Xiaoqian Wang,Jiangtao Li,Jian Kong,Peng Shi,Hanry Yu,Xingyu Jiang,Qiongyu Guo
Transarterial chemoembolization (TACE), the mainstay treatment of unresectable primary liver cancer that primarily employs nondegradable drug-loaded embolic agents to achieve synergistic vascular embolization and locoregional chemotherapy effects, suffers from an inferior drug burst behavior lacking long-term drug release controllability that severely limits the TACE efficacy. Here we developed gelatin-based drug-eluting microembolics grafted with nanosized poly(acrylic acid) serving as a biodegradable ion-exchange platform that leverages a counterion condensation effect to achieve high-efficiency electrostatic drug loading with electropositive drugs such as doxorubicin (i.e., drug loading capacity >34 mg/mL, encapsulation efficiency >98%, and loading time <10 min) and an enzymatic surface-erosion degradation pattern (∼2 months) to offer sustained locoregional pharmacokinetics with long-lasting deep-tumor retention capability for TACE treatment. The microembolics demonstrated facile microcatheter deliverability in a healthy porcine liver embolization model, superior tumor-killing capacity in a rabbit VX2 liver cancer embolization model, and stabilized extravascular drug penetration depth (>3 mm for 3 months) in a rabbit ear embolization model. Importantly, the microembolics finally exhibited vessel remodeling-induced permanent embolization with minimal inflammation responses after complete degradation. Such a biodegradable ion-exchange drug carrier provides an effective and versatile strategy for enhancing long-term therapeutic responses of various local chemotherapy treatments.
研究领域:
药学
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生物医学工程
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肿瘤学
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材料科学
✓ 已验证
DOI
PubMed
高影响因子
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