JOURNAL OF CONTROLLED RELEASE
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2020
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IF 7.727
Xiaoxuan Mai,Yanzhou Chang,Yuanyuan You,Lizhen He,Tianfeng Chen
High intensity focused ultrasound (HIFU) has been widely used in clinical treatment of cervical cancer for its non-invasiveness and sharp treatment margins with very low complication rates. However, how to intensify the therapeutic efficacy of HIFU by specifically focusing the ultrasound energy on targeting pathological tissues is still a bottleneck for it to realize successful cancer ablation. Herein, a multifunctional organic-inorganic hybrid nanovesicles, by coating ultrathin silica shell on the surface of poly (lactic- co -glycolic acid) (PLGA) loaded with perfluorocarbon (PFOB), hydrophobic antitumor ruthenium complex (RuPOP) and superparamagnetic Fe 3 O 4 , has been designed to achieve synchronous ultrasound (US)/magnetic resonance imaging (MR) dual mode imaging-guided HIFU-triggered chemotherapy. The introduction of PFOB in this nanosystem could cause phase transition and make it gasification to cause collapse of the outer ultrathin silicon shell under HIFU irradiation, which results in enhanced intensive mechanical stress during blasting and enhanced therapeutic effect. The blasting behavior of this nanosystem triggered by HIFU also induced the on-demand RuPOP burst release in tumor site, thus maximizing the inhibition on residual tumor induced by inhomogeneous HIFU ablation. Taken together, this treatment strategy could overcome the inevitable tumor recurrence and significantly reduces systemic side effects of HIFU, thus could be further developed for noninvasive cancer therapy.
研究领域:
医学
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生物工程
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影像学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2022
·
IF 7.033
Ni Fang,Jia Liu,Jingxin Hou,Yixin Zhong,Ying Luo,Liu Hu,Wenli Zhang,Junrui Wang,Jie Xu,Jun Zhou,Yu Zhang,Haitao Ran,Dajing Guo
Background Arterial thrombosis is a serious threat to human health. Recently, many thrombus-targeted nanoparticles (NPs) have been constructed for detecting thrombi or monitoring thrombolysis, but their thrombus-targeting performance is limited. Considering this drawback, we designed a specific bionic system with enhanced thrombus-targeting ability.Materials and Methods In the bionic system, gelatin was chosen as a carrier, and Fe3O4 served as a magnetic navigation medium and a magnetic resonance (MR) imaging agent. The CREKA peptide, which targets fibrin, was conjugated to the surface of gelatin to prepare targeted NPs (TNPs), which were then engulfed by macrophages to construct the bionic system. At the targeted site, the bionic system released its interior TNPs under low-intensity focused ultrasound (LIFU) irradiation. Moreover, the targeting performance was further improved by the conjugated CREKA peptide.Results In this study, we successfully constructed a bionic system and demonstrated its targeting ability in vitro and in vivo. The results indicated that most TNPs were released from macrophages under LIFU irradiation at 2 W/cm2 for 10 min in vitro. Additionally, the enhanced thrombus-targeting ability, based on the natural tropism of macrophages toward inflammatory thrombi, magnetic navigation and the CREKA peptide, was verified ex vivo and in vivo. Moreover, compared with the bionic system group, the group treated with TNPs had significantly decreased liver and spleen signals in MR images and significantly enhanced liver and spleen signals in fluorescence images, indicating that the bionic system is less likely to be cleared by the reticuloendothelial system (RES) than TNPs, which may promote the accumulation of the bionic system at the site of the thrombus.Conclusion These results suggest that the magnet-guided bionic system with LIFU responsiveness is an excellent candidate for targeting thrombi and holds promise as an innovative drug delivery system for thrombolytic therapy.
研究领域:
医学
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纳米生物技术
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影像学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
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IF 5.8
Xiyuan Yi,Yong Luo,Qi Zhou,Jun Wang,Zengtao Yang
Insulin therapy is the most effective way to control the blood glucose value of diabetic patients. The most effective administration route for insulin is subcutaneous injection because bioavailability for non-injection administration is low and unstable. However, patients often need a multiple daily insulin injection regimen to control basal and postprandial blood glucose, which causes various complications. Controlled pulsatile drug release technology using ultrasound as an external stimulus source is a very promising method to avoid multiple injections of insulin. However, most of the drug-loaded microbubbles used for ultrasound-mediated treatment have a short half-life, which limits their use in controlled pulsatile drug release. More importantly, how to control insulin release is still a challenge. In this paper, chitosan poly-acrylic acid nanobubbles as drug carriers of insulin were prepared to achieve a visually controlled pulsatile release of insulin triggered by focused ultrasound. The experimental results in vivo demonstrated that nanobubbles were stable enough to achieve long-term visualization for 7 days after intramuscular injection in rats. Under the guidance of ultrasound imaging, it is visible to find the position and observe the gray values change of nanobubbles. Thus, when triggered by focused ultrasound, the amount of insulin could be accurately pulsatile released from nanobubbles. In vivo experiments in rats showed that the visually controlled pulsatile release of insulin could be achieved for a long time, up to 3 consecutive days. The blood glucose level could be repeatedly reduced by focused ultrasound irradiation with just one injection. Our research provided a promising way for visually controlled pulsatile release of insulin, which would significantly reduce the injection frequency of insulin.
研究领域:
药剂学
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生物医学工程
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糖尿病治疗
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Yaotai Wang,Chun Chen,Yong Luo,Jie Xiong,Yu Tang,Haiyan Yang,Lu Wang,Fujie Jiang,Xuan Gao,Die Xu,Huanan Li,Qi Wang,Jianzhong Zou
Purpose The high-intensity focused ultrasound (HIFU) ablation of tumors is inseparable from synergistic agents and image monitoring, but the existing synergistic agents have the defects of poor targeting and a single imaging mode, which limits the therapeutic effects of HIFU. The construction of a multifunctional biological targeting synergistic agent with high biosafety, multimodal imaging and targeting therapeutic performance has great significance for combating cancer.Methods Multifunctional biological targeting synergistic agent consisting of Bifidobacterium longum (B. longum), ICG and PFH coloaded cationic lipid nanoparticles (CL-ICG-PFH-NPs) were constructed for targeting multimode imaging, synergistic effects with HIFU and imaging-guided ablation of tumors, which was evaluated both in vitro and in vivo.Results Both in vitro and in vivo systematical studies validated that the biological targeting synergistic agent can simultaneously achieve tumor-biotargeted multimodal imaging, HIFU synergism and multimodal image monitoring in HIFU therapy. Importantly, the electrostatic adsorption method and the targeting of B. longum to tumor tissues allow the CL-ICG-PFH-NPs to be retained in the tumor tissue, achieve the targeting ability of synergistic agent. Multimodal imaging chose the best treatment time according to the distribution of nanoparticles in the body to guide the efficient and effective treatment of HIFU. CL-ICG-PFH-NPs could serve as a phase change agent and form microbubbles that can facilitate HIFU ablation by mechanical effects, acoustic streaming and shear stress. This lays a foundation for the imaging and treatment of tumors.Conclusion In this work, a biological targeting synergistic agent was successfully constructed with good stability and physicochemical properties. This biological targeting synergistic agent can not only provide information for early diagnosis of tumors but also realize multimodal imaging monitoring during HIFU ablation simultaneously with HIFU treatment, which improves the shortcomings of HIFU treatment and has broad application prospects.
研究领域:
医学影像学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
PHYSICS IN MEDICINE AND BIOLOGY
·
2022
·Vol. 67
·期 19
·195005
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IF 4.174
Qianwen Huang,Yun Zhou,Ke Li,Lei Pan,Yuan Liu,Jingfeng Bai,Xiang Ji
Objective. This study is aimed to explore the effects of vascular and sonication parameters on ex vivo vessel sonicated by high-intensity focused ultrasound. Approach. The vascular phantom embedding the polyolefin tube or ex vivo vessel was sonicated. The vascular phantom with 1.6 and 3.2 mm tubes was sonicated at three acoustic powers (2.0, 3.5, 5.3 W). The occlusion level of post-sonication tubes was evaluated using ultrasound imaging. The vascular phantom with the ex vivo abdominal aorta of rabbit for three flow rates (0, 5, 10 cm s−1) was sonicated at two acoustic powers (3.5 and 5.3 W). Different distances between focus and posterior wall (2, 4, 6 mm) and cooling times (0 and 10 s) were also evaluated. The diameter of the sonicated vessel was measured by B-mode imaging and microscopic photography. Histological examination was performed for the sonicated vessels. Main results. For the 5 cm s−1 flow rate, the contraction index of vascular diameter (Dc) with 5.3 W and 10 s cooling time at 2 mm distance was 39 ± 9% (n = 9). With the same parameters except for 0 cm s−1 flow rate, the Dc was increased to 45 ± 7% (n = 4). At 3.5 W, the Dc with 5 cm s−1 flow rate was 23 ± 15% (n = 4). The distance and cooling time influenced the lesion along the vessel wall. Significance. This study has demonstrated the flow rate and acoustic power have the great impact on the vessel contraction. Besides, the larger lesion covering the vessel wall would promote the vessel contraction. And the in vivo validation is required in the future study.
研究领域:
生物医学工程
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超声技术
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血管研究
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产品关联
DOI
PubMed
高影响因子
Materials Horizons
·
2025
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IF 10.7
Jieying Zhang,Pengrui Wang,Lingkai Meng,Xiaohe Li,Fang Li,Na Kong,Xingjun Zhu
Emerging immunotherapies have demonstrated remarkable potential in cancer treatment. However, persistent challenges including insufficient immune activation and limited tumor infiltration remain unresolved. Here, we introduce focused-ultrasound (FUS) responsive artificial killer cells (AKCs), a novel biomimetic system integrating functions of natural killer (NK) cells, dendritic cells (DCs) and macrophages for closed-loop tumor immunotherapy. AKCs consist of lanthanide nanoparticles integrated within a hybrid lipid membrane, which not only improves biocompatibility but also enables real-time monitoring through near-infrared (NIR) imaging. Compared to traditional liposomal formulations, AKCs demonstrate superior tumor targeting and retention properties, significantly improving the reliability of diagnostics and therapeutic efficacy. The innovative use of FUS allows for controlled release of copper cations, which, in conjunction with the recruitment of dendritic cells via RANTES (Regulated on Activation, Normal T-cell Expressed and Secreted) cytokine release, transforms the immunosuppressive tumor microenvironment to immunologically active states. Cuproptosis induced by AKCs can significantly enhance tumor elimination efficacy. Tumor bearing mice exhibited prolonged survival and tumor regression with AKCs exhibiting superior tumor targeting and sustained antitumor effects. This research highlights a multifaceted approach to cancer immunotherapy, combining innate and adaptive immune activation mechanisms, thereby suggesting a promising direction for future advancements in targeted cancer therapies.
研究领域:
生物医学工程
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肿瘤学
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免疫学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Small Structures
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2024
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IF 13.9
Wenli Zhang,Maoyuan Sun,Lian Xu,Sijin Chen,Xiyue Rong,Junrui Wang,Jia Liu,Bo Liu,Jie Xu,Ying Luo,Qianying Du,Yi Wang,Yun Liu,Zhigang Wang,Haitao Ran,Dajing Guo
Owing to the short half-life, restricted targeting capability, and high bleeding risk associated with thrombolytic drugs, safe and effective thrombolytic therapy remains challenging. Based on the natural targeting and immune escape functions of platelets during thrombosis, spatiotemporally controlled nanobubbles (PAF@M) are developed to specifically target thrombus sites. These nanobubbles are designed by loading an air core of perfluoropentane (PFP) and l -arginine within a poly(lactic -co -glycolic acid) shell and coating it with a platelet membrane. Under stimulation with low-intensity focused ultrasound (LIFU), physical shear stress promotes deep penetration of the nanobubbles into the thrombus. Moreover, the liquid–gas phase transition of PFP and the release of nitric oxide synergistically enhance ultrasonic cavitation to disrupt the thrombus structure. In terms of mechanism, these gas molecules induce acoustic pore action to disrupt the fibrin network structure, loosening the interior of the thrombus, and act specifically on the surfaces of red blood cells and activated platelets, launching a comprehensive attack on the thrombus. It is believed that PAF@M nanobubbles will delay the progression of thrombosis and achieve safe and highly effective thrombolytic therapy. This simple LIFU response principle has the potential to be a safer and more effective alternative to current pharmaceutical approaches.
研究领域:
医学工程
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生物医学
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药物递送
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DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
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2025
·Vol. 39
·期 2
·e6067
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IF 1.7
Jiale Liu,Rongfei Yuan,Qi Wang,Hai Qiao,Yuling Yang,Siyu Yang,Hua Zhang,Chang Chen
High-intensity focused ultrasound (HIFU) is a noninvasive soft tissue ablation technique, which utilizes ultrasound energy to induce thermal coagulation necrosis in targeted tissues. Whether this high energy causes side effects in vivo, such as the formation of peptide bonds, has not been fully investigated. Glycylglycine is the simplest dipeptide and hence is often used as a model compound for peptide studies. In this study, we developed and validated a sensitive quantification method based on ion-exchange solid-phase extraction, liquid chromatography, and tandem mass spectrometry (SPE-LC-MS/MS) for the analysis of glycylglycine without derivatization, and then used it to evaluate whether HIFU promoted peptide bond formation in aqueous solution (without enzymes) and plasma (with enzymes). The results showed that strong cation exchange SPE significantly reduced the matrix effect and improved the sensitivity of the LC-MS/MS method. No formation of glycylglycine in the aqueous solution or plasma was observed following HIFU irradiation.
研究领域:
生物化学
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医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-22
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IF 10.6
Ren Li,Wang Yaotai,Tang Yu,Wang Fang,Du Yan,Ou Xia,Lin Li,Zhang Zhong,Ding Yan,Wu Meixian,Zhou Yijun,Zhang Mingyang,Wang Qi,Zou Jianzhong
Focused ultrasound ablation surgery (FUAS) is a minimally invasive treatment option that has been utilized in various tumors. However, its clinical advancement has been hindered by issues such as low safety and efficiency, single image guidance mode, and postoperative tumor residue. To address these limitations, this study aimed to develop a novel multi-functional gas-producing engineering bacteria biological targeting cooperative system. Pulse-focused ultrasound (PFUS) could adjust the ratio of thermal effect to non-thermal effect by adjusting the duty cycle, and improve the safety and effectiveness of treatment.The genetic modification of Escherichia coli ( E.coli ) involved the insertion of an acoustic reporter gene to encode gas vesicles (GVs), resulting in gas-producing E.coli (GVs -E.coli ) capable of targeting tumor anoxia. GVs -E.coli colonized and proliferated within the tumor while the GVs facilitated ultrasound imaging and cooperative PFUS. Additionally, multifunctional cationic polyethyleneimine (PEI)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEI-PLGA/EPI/PFH@Fe 3 O 4 ) containing superparamagnetic iron oxide (SPIO, Fe 3 O 4 ), perfluorohexane (PFH), and epirubicin (EPI) were developed. These nanoparticles offered synergistic PFUS, supplementary chemotherapy, and multimodal imaging capabilities.GVs -E.coli effectively directed the PEI-PLGA/EPI/PFH@Fe 3 O 4 to accumulate within the tumor target area by means of electrostatic adsorption, resulting in a synergistic therapeutic impact on tumor eradication.In conclusion, GVs -E.coli -mediated multi-functional nanoparticles can synergize with PFUS and chemotherapy to effectively treat tumors, overcoming the limitations of current FUAS therapy and improving safety and efficacy. This approach presents a promising new strategy for tumor therapy. Graphical
研究领域:
生物医学工程
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肿瘤学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
Cell Reports Medicine
·
2024
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IF 11.7
Yaozhang Yang,Yuanyuan Wang,Fengyi Zeng,Yuhao Chen,Zhiyi Chen,Fei Yan
Our previous work developed acoustic response bacteria, which enable the precise tuning of transgene expression through ultrasound. However, it is still difficult to visualize these bacteria in order to guide the sound wave to precisely irradiate them. Here, we develop ultrasound-visible engineered bacteria and chemically modify them with doxorubicin (DOX) on their surfaces. These engineered bacteria (Ec@DIG-GVs) can produce gas vesicles (GVs), providing a real-time imaging guide for remote hyperthermia high-intensity focused ultrasound (hHIFU) to induce the expression of the interferon (IFN)-γ gene. The production of IFN-γ can kill tumor cells, induce macrophage polarization from the M2 to the M1 phenotype, and promote the maturation of dendritic cells. DOX can be released in the acidic tumor microenvironment, resulting in immunogenic cell death of tumor cells. The concurrent effects of IFN-γ and DOX activate a tumor-specific T cell response, producing the synergistic anti-tumor efficacy. Our study provides a promising strategy for bacteria-mediated tumor chemo-immunotherapy.
研究领域:
医学
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生物技术
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Jie Yang,Min Liao,Zhenru Wu,Xiaodi Liu,Zhiwen Zheng,Wenhui Wang,Zhe Wu,Qiang Lu
The activation of immune-stimulatory molecules is critical for effective antitumor immunotherapy. Mechanical high-intensity focused ultrasound (mHIFU) sustains this activation in tumor cell debris through cavitation. To enhance cavitation, perfluorohexane nanodroplets (NDs-PFH) were utilized in this study to lower the cavitation threshold during mHIFU ablation. Our results showed that NDs-PFH combined with mHIFU induced 77.2 % Hepa 1–6 tumor cells death, and activated the release of damage-associated molecular patterns (such as HMGB1, CRT, and ATP), enhancing dendritic cell maturation (20.2 %) and T cell activation (1.8 % of TNF-α + and 2.7 % of IFN-γ + ). In vivo , the combination of NDs-PFH and mHIFU effectively suppressed both primary and distant untreated tumors, reducing the tumor volume by 83.3 % (from 657.4 mm 3 to 110.0 mm 3 ) and metastatic tumor volume by 76.6 % (from 365.5 mm 3 to 85.6 mm 3 ) through enhanced anticancer immune response and a robust abscopal effect. Furthermore, combining NDs-PFH with mHIFU significantly enhanced the efficacy of immune checkpoint inhibitors in liver cancer. When combined with αPD-1 therapy, tumor inhibition improved by 30 % (from 63.6 mm 3 to 19.3 mm 3 ) compared to αPD-1 monotherapy. These results highlight the potential of combining mHIFU with a PFH nano-loaded drug delivery system as a promising strategy for advancing antitumor immunotherapy. Statement of significance Mechanical high-intensity focused ultrasound (mHIFU) can ablate tumors via cavitation effects, however, achieving these effects typically requires an extremely high cavitation threshold. In this study, we utilized widely used perfluorohexane nanodroplets (NDs-PFH) to effectively lower the cavitation threshold. The tumor cell debris generated by the combination of NDs-PFH and mHIFU not only induced immunogenic cells death but also activated antitumor immune responses within the tumor microenvironment. Additionally, our findings demonstrated that this combination elicited a significant abscopal effect and enhanced the efficacy of immunotherapy.
研究领域:
肿瘤学
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医学物理
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOLIA HISTOCHEMICA ET CYTOBIOLOGICA
·
2023
·Vol. 61
·期 1
·47-55
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IF 1.5
Weixing Mo Qingqing Yu Xiufeng Kuang Ting He Jun Lou Rongjun Tang Ke Zhang Lingdi Li Linfang Zhao
Introduction. Focused ultrasound (FUS) is a non-invasive tumor therapy technology emerging in recent years, which can treat various solid tumors. However, it is unclear whether FUS can affect the pyroptosis of colon cancer (CC) cells. Here, we analyzed the effect of FUS on pyroptosis in the orthotopic CC model. Material and methods. After an orthotopic CC mouse model was constructed by injecting CT26-Luc cells, BABL/C mice were allocated to the normal, tumor, FUS, and FUS + BAY11-7082 (pyroptosis inhibitor) groups. We monitored the tumor status of the mice through in vivo fluorescence image analysis. The histopathological injury of the intestinal tissue and the expression of IL-1β, IL-18, caspase-recruitment domain (ASC), cleaved caspase-1, gasdermin D (GSDMD), and NLRP3 of the CC tumors were examined utilizing hematoxylin and eosin staining, immunohistochemical assay, and Western blot. Results. FUS restrained the fluorescence intensity of the tumors in orthotopic CC mice, while FUS-mediated suppression of the bioluminescent signal of the tumors was alleviated by BAY11-7082. FUS was found to relieve the injury of the intestinal tissues in CC mice as revealed by morphology. Furthermore, the expressions of IL-1β, IL-18, GSDMD, ASC, cleaved caspase-1, and NLRP3 of the CC tumors in the FUS group were higher than those in the tumor group, while BAY11-7082 addition partly reversed the FUS’s effects on orthotopic CC model mice. Conclusions. Our results pointed out that FUS presented anti-tumor activity in experimental CC, and its mechanism was correlated with the promotion of pyroptosis.
研究领域:
肿瘤学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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