Small
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2026
·
IF 11.8
Gaofeng Shu,Kai Li,Shiji Fang,Qianhui He,Jiayi Shi,Peiyao Liu,Fazong Wu,Min Xu,Weiqian Chen,Kai Yan,Jin Su,Jiansong Ji,Minjiang Chen
The therapeutic efficacy of transarterial chemoembolization (TACE) is strongly limited by the hypoxic and immunosuppressive tumor microenvironment (TME). Herein, monodisperse perfluorooctyl bromide (PFOB)-loaded fucoidan/gelatin microspheres (P@FGMS) with excellent oxygen-carrying capability were prepared for enhanced TACE treatment of hepatocellular carcinoma (HCC). It was found that the introduction of fucoidan endowed P@FGMS with excellent electrostatic affinity for positively charged doxorubicin (DOX) and metformin (MET), enabling their efficient co-loading and sustained release. The resulting drug-loaded microspheres (DMP@FGMS) largely enhanced chemotherapy sensitivity through an in-outside hypoxia remodeling strategy: the supplement of exogenous O 2 via PFOB and inhibition of intracellular oxygen consumption by MET. Notably, DMP@FGMS could not only modulate hypoxic TME, but also generate intracellular ROS and disrupt the redox homeostasis, thereby triggering cancer ferroptosis. Moreover, DMP@FGMS effectively remodeled the immunosuppressive TME by alleviating tumor hypoxia and inducing immunogenic cell death (ICD), thereby enhancing CD8 + T cell infiltration while reducing immunosuppressive cell populations. Consequently, DMP@FGMS could effectively suppress tumor growth in an orthotopic HCC rat model, with this effect further potentiated by combination with immune checkpoint blockade therapy. Therefore, this study demonstrates that DMP@FGMS is a potent embolic agent capable of remodeling the hypoxic/immunosuppressive TME, representing a promising strategy for TACE treatment of HCC.
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
·
IF 8.2
Minjiang Chen,Xiaoju Guo,Lin Shen,Jiayi Ding,Junchao Yu,Xiaoxiao Chen,Fazong Wu,Jianfei Tu,Zhongwei Zhao,Mitsutoshi Nakajima,Jingjing Song,Gaofeng Shu,Jiansong Ji
Transarterial chemoembolization (TACE) is an important approach for the treatment of unresectable hepatocellular carcinoma (HCC). However, the lactic acid-induced acidic tumor microenvironment (TME) may reduce the therapeutic outcome of TACE. Herein, monodispersed gelatin microspheres loaded with calcium carbonate nanoparticles (CaNPs@Gel-MS) as novel embolic agents were prepared by a simplified microfluidic device. It was found that the particle size and homogeneity of as-prepared CaNPs@Gel-MS were strongly dependent on the flow rates of continuous and dispersed phases, and the inner diameter of syringe needle. The introduction of CaNPs provided the gelatin microspheres with an enhanced ability to encapsulate the chemotherapeutic drug of DOX, as well as a pH-responsive sustained drug release behavior. In vitro results revealed that CaNPs@Gel-MS could largely increase the cellular uptake and chemotoxicity of DOX by neutralizing the lactic acid in the culture medium. In addition, CaNPs@Gel-MS exhibited an excellent and persistent embolic efficiency in a rabbit renal model. Finally, we found that TACE treatment with DOX-loaded CaNPs@Gel-MS (DOX/CaNPs@Gel-MS) had a much stronger ability to inhibit tumor growth than the DOX-loaded gelatin microspheres without CaNPs (DOX@Gel-MS). Overall, CaNPs@Gel-MS could be a promising embolic microsphere that can significantly improve anti-HCC ability by reversing lactic acid-induced chemotherapy resistance during TACE treatment.
研究领域:
医学
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肿瘤学
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生物材料学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Qing Shi,Xingxing Zhang,Minmin Wu,Yuhan Xia,Yating Pan,Jialu Weng,Na Li,Xingjie Zan,Jinglin Xia
Lipiodol-based transcatheter arterial chemoembolization (TACE) is currently the predominant and first-line treatment option recommended by the global standard for unresectable hepatocellular carcinoma (HCC). However, the unstable emulsion of Lipiodol causes a substantial proportion of chemotherapy drugs to enter the circulation system, leading to poor accumulation in cancer tissues and unexpected side effects of chemotherapy drugs. Herein, we emulsified Lipiodol with a pH-sensitive drug delivery system assembled from hexahistidine and zinc ions (HmA) with a super-high loading capacity of doxorubicin (DOX) and a promising ability to penetrate bio-barriers for the effective treatment of HCC by TACE. In vitro tests showed that DOX@HmA was comparable to free DOX in killing HCC cells. Impressively, during the in vivo TACE treatment, the anti-tumor efficacy of DOX@HmA was significantly greater than that of free DOX, indicating that DOX@HmA increased the accumulation of DOX in tumor. Emulsifying Lipiodol with pH-sensitive DOX@HmA significantly inhibited cell regeneration and tumor angiogenesis and decreased the systemic side effects of chemotherapy, especially by suppressing pulmonary metastasis in liver VX2 tumors in rabbits by inhibiting epithelial–mesenchymal transition (EMT). Emulsifying tumor microenvironment-responsive drug delivery systems (DDSs) with Lipiodol could be a new strategy for clinical TACE chemotherapy with potentially enhanced HCC treatment.
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2020
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IF 4.545
Xihan Li,Hui Yu,Ying Huang,Yu Chen,Jialun Wang,Lei Xu,Feng Zhang,Yuzheng Zhuge,Xiaoping Zou
Background Transcatheter arterial chemoembolization (TACE) is extensively used in the treatment of advanced hepatocellular carcinoma (HCC). However, the efficacy of TACE is usually limited to secondary tumor hypoxia and hypoxia-related tumor angiogenesis. Methods In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres (SOR-CAT-PLGA MSs) encapsulating sorafenib (SOR) and catalase (CAT) were prepared by double-emulsion solvent diffusion method. Sorafenib inhibits tumor angiogenesis, and catalase decomposes hydrogen peroxide (H 2 O 2 ) to generate oxygen in the tumor. Results In vitro and in vivo , SOR -CAT-PLGA MSs could significantly improve the efficacy of hepatic artery embolization in the treatment of rabbit VX2 liver tumors, regulate tumor hypoxia and immunosuppressive microenvironment, then achieved near-complete and rapid necrosis of liver tumors. Conclusions The application of new SOR -CAT-PLGA MSs in hepatic artery chemoembolization of rabbit VX2 liver tumor is a promising approach to improve the therapeutic effect of liver tumors and has a broad clinical application prospect.
研究领域:
肿瘤学
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药理学
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生物医学工程
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Jin-Xin Huang,Wei-Hua Zhang,Ye-Ming Wu,Jian-Yu Hu,Huan Long,Hai-Dong Zhu,Jian-Qiong Zhang,Gao-Jun Teng,Fei Xiong
Drug-eluting bead transcatheter arterial chemoembolization (D-TACE) is one of the first-line treatment for intermediate hepatocellular carcinoma (HCC). However, the dual hypoxia microenvironment, due to inherent tumor hypoxia and TACE-induced hypoxia, triggers drug resistance in HCC. To address this challenge, the study develops multicavitary microspheres capable of encapsulating oxygen and harnessing magnetic hyperthermia to enhance oxygen permeability. The novel multicavitary oxygen-encapsulated magnetothermal drug-eluting microspheres (OTD-Ms) effectively reduce hypoxia-related proteins (HIF-1α, VEGF-A) and drug resistance (P-gp) both in vitro and in vivo. Moreover, these microspheres demonstrate improved TACE efficacy and enhance survival rates in a rabbit VX-2 tumor model, suggesting their potential for HCC treatment.
研究领域:
肿瘤学
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介入放射学
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生物医学工程
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DOI
PubMed
高影响因子
Materials Today Bio
·
2024
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IF 8.7
Jin-Xin Huang,Rui Yang,Huan Long,Jie Kong,Guo-Qiang Shao,Fei Xiong
Hepatocellular carcinoma (HCC) is a major public health threat due to its high incidence and mortality rates. Transcatheter arterial chemoembolization (TACE), the primary treatment for intermediate-to-advanced hepatocellular carcinoma (HCC), commonly utilizes embolic agents loaded with anthracycline-based cytotoxic drugs. Post-TACE, the hypoxic microenvironment in the tumor induced by embolization stimulates the formation of new blood vessels, potentially leading to revascularization and diminishing TACE's efficacy. In clinical practice, combined therapy for liver cancer using TACE and oral targeted drugs often encounters the limitation that targeted drugs cannot efficiently reach the tumor site following TACE. We have developed chondroitin sulfate microspheres (CMs) capable of encapsulating both the cytotoxic drug idarubicin (Ida) and the vascular inhibitor Lenvatinib (Len), thereby achieving a triple therapeutic effect on liver cancer: embolic starvation, drug toxicity, and efficient inhibition of neovascularization.
研究领域:
肿瘤学
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介入放射学
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药剂学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2026
·Vol. 24
·期 1
·562
·
IF 15
Chen Chao,Song Songlin,Wu Wenlong,Yu Ningjun,Zheng Chuansheng,Zhou Guofeng,Ren Yanqiao,Dong Xiangjun
Introduction Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC); however, TACE refractoriness remains a major clinical challenge. Increasing evidence suggests that post-embolization hypoxia-driven metabolic reprogramming, particularly dysregulated copper homeostasis, contributes to therapeutic resistance. Objective This study aimed to elucidate the role of copper metabolism in TACE-refractory HCC and to develop a mechanism-driven nanoembolic strategy targeting the copper chaperone ATOX1 to induce cuproptosis and reverse TACE refractoriness. Methods Clinical serum samples from HCC patients with TACE refractoriness or favorable response were analyzed for copper levels and copper transport–related proteins. A thermosensitive nanogel (Cu²⁺/DC_AC50@PNA) co-loaded with copper ions and the ATOX1 inhibitor DC_AC50 was synthesized and characterized. Its embolic performance, antitumor efficacy, and biosafety were evaluated in rabbit renal artery and VX2 orthotopic liver tumor models. In vitro assays using Huh-7 and LM3 cells under normoxic and hypoxic conditions assessed cell viability, migration, invasion, and cuproptosis-related signaling. Results Patients with TACE refractoriness exhibited significantly elevated serum copper levels and increased ATOX1 and ATP7B expression, indicating systemic copper dyshomeostasis. Cu²⁺/DC_AC50@PNA demonstrated favorable physicochemical properties, sustained embolic capability, and excellent biocompatibility. In vivo, this nanoembolization system markedly suppressed tumor growth, increased tumor necrosis, reduced metastasis, and prolonged survival compared with conventional cTACE. Mechanistically, Cu²⁺/DC_AC50@PNA disrupted intracellular copper transport, activated cuproptosis, inhibited HIF-1α/VEGF-mediated angiogenesis, and remodeled the tumor immune microenvironment by enhancing CD8⁺ T-cell infiltration. In vitro findings corroborated potent antitumor and anti-metastatic effects, particularly under hypoxic conditions. Conclusion Copper metabolism dysregulation is a defining feature of TACE-refractory HCC. Targeting ATOX1-mediated copper homeostasis using Cu²⁺/DC_AC50@PNA represents a novel and effective strategy to induce cuproptosis, overcome TACE refractoriness, and improve therapeutic outcomes in HCC. Graphical
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高影响因子
Acta Biomaterialia
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2021
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IF 8.947
Jiaojiao Li,Jihua Wang,Jianye Li,Xin Yang,Jiangling Wan,Chuansheng Zheng,Qing Du,Guofeng Zhou,Xiangliang Yang
Magnetic resonance imaging (MRI) has attracted increasing attention as a feasible alternative or adjunctive imaging modality for X-ray digital subtraction angiography because of the high tissue resolution and non-ionization radiation. In this study, a one-step electrospray method was developed to fabricate PVA microspheres encapsulated with in situ synthesized Fe 3 O 4 nanoparticles . Fe 3 O 4 @PVA microspheres were mono-dispersed black spheres with a wide range of sizes (262–958 µm). The in situ -synthesized Fe 3 O 4 nanoparticles were used as the contrast agent of MRI and the cross-linkers of PVA matrixes for the embolization purpose. In vivo evaluation of renal arteries of normal rabbits showed that Fe 3 O 4 @PVA microspheres had good embolic effect and enhanced capability of MRI. In vitro and in vivo biosafety assessment confirmed that Fe 3 O 4 @PVA microspheres had favorable biocompatibility. The DOX-loaded Fe 3 O 4 @PVA microspheres showed a typical drug-sustained release profile. These results suggest that the prepared DOX-loaded Fe 3 O 4 @PVA microspheres have the function of MRI, embolotherapy and chemotherapy. We expect our study could provide a simple and useful approach for the systematic design , fabrication, and application of a new type of magnetic microspheres as a triple-functional embolic agent for the development of MRI-guided TACE. Statement of significance Due to the low tissue resolution and hazardous ionization radiation of X-ray digital subtraction angiography, it is beneficial to study MR imaging embolic microspheres for the development of MRI-guided TACE. In this study, a one-step electrospray method was firstly developed to fabricate PVA microspheres encapsulated with in situ synthesized Fe 3 O 4 nanoparticles. Then, chemotherapeutic agent (DOX), contrast media of MRI (Fe 3 O 4 ) and embolic agent (PVA matrix) were combined together in one body (DOX-loaded Fe 3 O 4 @PVA microspheres) to achieve the triple effects of chemotherapy, MR imaging and embolization. This triple-functional embolic agent offers potential for the future development of MRI-guided TACE.
研究领域:
材料科学
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医学影像
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纳米技术
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生物医学工程
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DOI
PubMed
高影响因子
Materials Today Communications
·
2024
·
IF 3.7
Lan Zhang,Baoqu Zhang,Rongkang Yu,Shuyue Wu,Shugao Han,Rui Tang,Ruibo Zhao,Xiangdong Kong
Drug-loaded microspheres are widely used in transcatheter arterial chemoembolization (TACE). Controlled drug release from drug-loaded microspheres reduces systemic toxicity, thus necessitating the development of microspheres with controlled release properties. In this study, three different sizes of sodium hyaluronate microspheres (SH) were prepared by a one-step solution drying method using 1,4-butanediol diglycidyl ether (BDDE) as a crosslinking agent. The average sizes of the three SH microspheres (small, medium and large) were 410 μm, 550 μm and 750 μm, respectively. The morphology of the small-sized SH microspheres (SS-SH) was solid spherical; the medium-sized SH microspheres (MS-SH) were semi-hollow spherical; and the large-sized SH microspheres (LS-SH) had a bowl with an opening on one side and a cavity inside. A drug-loaded microsphere (DOX@SH) was prepared by immersing SH microspheres in a doxorubicin hydrochloride (DOX) solution. The average size of the three DOX@SH microspheres increased to 607 μm, 876 μm and 1187 μm, respectively. The encapsulation efficiencies of small, medium and large-sized SH microspheres reached 97.09 %, 96.73 % and 74.87 % at 2 h in a 2 mg/mL DOX solution. The maximum drug loadings of the small, medium and large-sized SH microspheres were 0.38, 0.38 and 0.33 mg DOX/mg SH, respectively. All sizes of DOX@SH microspheres could be controlled and sustained to release and reach equilibrium after 48 h. The cumulative release rates of small, medium and large-sized DOX@SH microspheres (SS-DOX@SH, MS-DOX@SH and LS-DOX@SH) at 72 h were 24.3 %, 28.1 % and 33.8 % in a release medium of pH 6.5, respectively. Blood compatibility and cytotoxicity tests demonstrated that SH microspheres exhibit good biocompatibility. The cytotoxicity of DOX@SH microspheres to HepG2 cells and the uptake of DOX in HepG2 cells showed effective anti-tumor activity. Simulated embolization in vitro experiments indicated that the small-sized DOX@SH microspheres had a good embolization effect for 500–800 μm and 300–500 μm blood vessels. These findings indicate that the newly developed DOX@SH microspheres can be used as a promising drug-loaded embolization agent to enhance the treatment of hepatocellular carcinoma.
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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DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2023
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IF 5.2
Luping Chen,Shixiang Liu,Fengyuan Gao,Hailin Cong,Bing Yu,Youqing Shen
Transcatheter arterial chemoembolization (TACE) is one of the common methods of treating tumors and usually requires an accompanying injection of an exogenous contrast agent, but the exogenous contrast agent is highly susceptible to removal by blood flow , which greatly reduces the efficiency of the operation. Here, we developed a uniformly sized Ag 2 S/BaSO 4 /DOX@PEGDAMS that integrates embolization, drug loading, and visualization with a microfluidic device . The microspheres can be imaged stably under NIR-II/X-ray for a long time, and the luminescence of NIR-II is better than that of X-ray. This breaks the limitations of conventional X-ray-only imaging of embolic microspheres . The microscope images and scanning electron microscope EDS results showed that the microspheres were regularly spherical with uniform particle size, and the signature elements such as Ag, S, and Ba were uniformly distributed in the microspheres. In vitro cytotoxicity assays and apoptosis assays have demonstrated that the microspheres have good biocompatibility and can effectively inhibit tumor cell growth due to the presence of DOX. The ability of microspheres to aggregate in blood vessels and block blood flow was verified by modeling and embolizing in rabbit ear tumors. In conclusion, Ag 2 S/BaSO 4 /DOX@PEGDAMS shows excellent embolization, drug loading, and imaging capabilities, and has the potential to be used for TACE and other diseases requiring interventional embolization therapy.
研究领域:
生物医学工程
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药学
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癌症治疗
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材料科学
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Meirong Zhang,Shidong Zou,Dingwen Shi,Qingqing Zhang,Mengqin Guo,Xiangliang Yang,Yanbing Zhao
Transcatheter arterial chemoembolization (TACE) exhibits an important role in the treatment of some solid tumors. However, incomplete embolization and angiogenesis-induced tumor relapse and metastasis remain the biggest challenges for TACE. Here, we synthesized metformin-conjugated poly(N-acryloyl glycinamide) ( p Met) nanogels for precisely synergizing TACE with radiofrequency ablation (RFA) to improve antitumor efficacy. p Met nanogels exhibited RF-heating effect and UCST-type gel-sol phase transition, with high performance of sol syringeability, gel strength and thermal stability. Meanwhile, p Met nanogels showed distinct cytotoxicity and suppression of CD24. By the synergistic efficacy with RF-heating, p Met nanogels exhibited significant tumor regression (0.37 ± 0.5) over 36 d in H22-bearing mice. p Met nanogels further down-regulated the levels of PD-1 and Tim-3 of CD8 + T cells and CD25 and CD38 of CD4 + T cells, suggesting their improvement on tumor immunosuppressive microenvironment. The blood-vessel embolization of p Met nanogels was well validated on rabbit ear vessel model. p Met nanogels provide a new paradigm for constructing RF responsive embolic platform.
研究领域:
肿瘤学
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生物医学工程
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药学
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yanqiao Ren,Yusheng Guo,Bo Sun,Licheng Zhu,Wenlong Wu,Bin Liang,Xiangjun Dong,Chuansheng Zheng
Transarterial chemoembolization (TACE) requires the complete embolization of tumor vessels. However, after embolization, tumor hypoxia and angiogenesis increase, and copper ions (Cu 2+ ) play a key role in the regulation of angiogenesis. Decreasing the undesirable release of Cu 2+ into serum and tumor tissues is a major challenge in the use of TACE. In this study, we constructed an adhesive injectable thermosensitive hydrogel (poly(N-isopropylacrylamide-codopamine methacrylamide), PND) loaded with a small Cu chelator (SO-N) for use in synergistic tumor embolization; this agent is called PNDS. SO-N chelates Cu 2+ in a highly selective manner and can effectively consume the biocopper that is involved in angiogenesis. In addition, the adhesive thermosensitive hydrogel rapidly formed a gel in situ , which further inhibited the local blood ny to the tumor and accelerated ischemic necrosis. Moreover, the ability of PNDS to efficiently chelate Cu 2+ and inhibit angiogenesis was investigated in vitro . Our in vivo experiments demonstrated that PNDS can promote tumor necrosis, reduce tumor Cu 2+ levels, inhibit angiogenesis and tumor metastasis, and greatly prolong rabbit survival. This study is the first to show elevated serum Cu 2+ levels in liver cancer patients with TACE failure/refractoriness; PNDS provides a promising approach for improving the efficacy of TACE for liver cancer by regulating Cu homeostasis.
研究领域:
肿瘤学
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药学
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生物医学工程
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DOI
高影响因子
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