BIOMATERIALS
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2014
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IF 8.312
Kun Zhang,Hangrong Chen,Faqi Li,Qi Wang,Shuguang Zheng,Huixiong Xu,Ming Ma,Xiaoqing Jia,Yu Chen,Juan Mou,Xia Wang,Jianlin Shi
Aiming at substantially enhanced efficacy and biosafety of clinical HIFU therapy, a natural solid medium, L-menthol (LM), characteristic of mild and controllable “solid-liquid-gas” (SLG) tri-phase transition, was adopted, instead of those conventional explosive liquid–gas (LG) bi-phase transitional media, in constructing a multifunctional theranostic system. Owing to the continuous and controllable characteristics of SLG tri-phase transition, such a novel tri-phase transition-based theranostic system has been demonstrated of the repeatedly enhanced HIFU efficacy ex vivo and in vivo under once intravenous injection and the significantly improved treatment precision, controllability and biosafety when comparing to the traditional bi-phase transition medium, perfluorohexane (PFH), thus promising great application potential in clinical HIFU treatment. Moreover, this theranostic system has been demonstrated a long blood-circulation lifetime and continuous accumulation in tumor in 24 h, which is very beneficial for the enhanced tumor ablation in vivo along with SLG tri-phase transition. More importantly, after loading multiple model drugs and real drug, such a theranostic system presents a HIFU-mediated temperature-responsive drug release property, and depending on the versatile miscibility of LM, co-loadings with hydrophobic and hydrophilic drugs are also achieved, which provides the possibility of synergistic treatment combining HIFU therapy and chemotherapy.
研究领域:
医学影像学
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肿瘤学
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药剂学
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DOI
高影响因子
Applied Sciences-Basel
·
2018
·Vol. 8
·期 4
·609
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IF 1.689
Shilei Liu,Yanye Yang,Chenghai Li,Xiasheng Guo,Juan Tu,Dong Zhang
High intensity focused ultrasound (HIFU) has been proven to be promising in non-invasive therapies, in which precise prediction of the focused ultrasound field is crucial for its accurate and safe application. Although the Khokhlov–Zabolotskaya–Kuznetsov (KZK) equation has been widely used in the calculation of the nonlinear acoustic field of HIFU, some deviations still exist when it comes to dispersive medium. This problem also exists as an obstacle to the Westervelt model and the Spherical Beam Equation. Considering that the KZK equation is the most prevalent model in HIFU applications due to its accurate and simple simulation algorithms, there is an urgent need to improve its performance in dispersive medium. In this work, a modified KZK (mKZK) equation derived from a fractional order derivative is proposed to calculate the nonlinear acoustic field in a dispersive medium. By correcting the power index in the attenuation term, this model is capable of providing improved prediction accuracy, especially in the axial position of the focal area. Simulation results using the obtained model were further compared with the experimental results from a gel phantom. Good agreements were found, indicating the applicability of the proposed model. The findings of this work will be helpful in making more accurate treatment plans for HIFU therapies, as well as facilitating the application of ultrasound in acoustic hyperthermia therapy.Keywords:KZK equation;fractional order derivative;ultrasound hyperthermia;HIFU;acoustic simulation;Kramers–Kronig relation
研究领域:
医学物理
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生物医学工程
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
·
IF 13.2
Yinglin Zhou,Xinchang Huang,Dezhou Wu,Xiaomei Xie,Hechun Li,Qi Wang,Yan Liao,Huanan Li
High-intensity focused ultrasound (HIFU) represents a game-changing breast-conserving treatment, with its induced immune response playing a crucial role in prognosis. However, the low immunogenicity and immunosuppressive microenvironment of tumors after surgery have prevented HIFU from generating strong antitumor immune responses, resulting in tumor recurrence and metastasis. Herein, we developed CaCO 3 -loaded metal–organic frameworks (MOFs) comprising Mn 2+ , hypoxia-activated prodrug banoxantrone (AQ4N), and stimulator of interferon genes (STING) agonist SR-717 to enhance HIFU-induced antitumor immunotherapy. Upon effective accumulation and drug release within tumor microenvironment (TME), MOFs exploit HIFU-exacerbated hypoxia to activate AQ4N, thereby inducing immunogenic cell death and enhancing tumor immunogenicity. Meanwhile, Mn 2+ enhances the activity of SR-717, synergistically amplifying STING activation and effectively promoting immune cell infiltration. Moreover, CaCO 3 complements immunotherapy by depleting lactate in TME, remodeling the immune microenvironment. As a result, MOFs enhance HIFU postoperative antitumor immune responses, significantly inhibiting tumor recurrence and metastasis. This work provides valuable insights to improve the prognosis of all surgical procedures, including HIFU.
研究领域:
肿瘤学
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免疫学
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生物医学工程
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药学
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产品关联
DOI
高影响因子
Advanced Science
·
2025
·
IF 14.1
Xiaomin Su,Yang Wang,Xifeng Qin,Yaqiong Xiao,Boshu Ouyang,Lina Hu,Lin Kang,Ruizhe Xu,Ce Xu,Zanya Sun,Chenyu Sun,Huishu Guo,Zhiqing Pang,Shun Shen
The high heterogeneity of basal-like breast cancer (BLBC) and the absence of effective therapeutic targets pose ongoing treatment challenges. Pyroptosis, a type of cell death characterized by cell swelling and membrane perforation, offers a promising therapeutic weathervane for BLBC, particularly when induced by physical therapies. In this study, a high-intensity focused ultrasound (HIFU)-driven targeted pyroptosis strategy is developed for BLBC therapy. Through integration of HIFU-driven gene regulation analysis and bioinformatics analysis of pyroptosis-related genes from the TCGA dataset, 20 potential pyroptosis inducers are identified to work synergistically with HIFU. Mitoxantrone, a promising inducer, is encapsulated in platelet membrane-hybridized liposomes to enhance targeted delivery and therapeutic efficacy. Importantly, the combination of HIFU and Plp enhanced tumor delivery of liposomes by 2.46 fold and dramatically inhibited tumor growth, with 50% of female BALB/c mice remaining tumor-free compared to liposome-only treatment. Mechanistically, HIFU significantly downregulated the expression of histone deacetylases 4 and 9, while promoting cathepsin-L (CTSL) gene transcription. Simultaneously, Plp and HIFU synergistically suppressed BCL-2 via CTSL, increasing ROS production. This activated Caspase8 and the NLRP3 inflammasome, leading to GSDMC cleavage and initiating pyroptosis. Collectively, this study provides an innovative pyroptosis therapy strategy combining physical treatment and chemotherapy for BLBC and other refractory diseases.
研究领域:
肿瘤学
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分子生物学
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转化医学
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纳米医学
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细胞死亡机制
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生物信息学
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基因调控
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2021
·
IF 4.939
Chao Li,Yao Lu,Lili Cheng,Xiaoge Zhang,Jun Yue,Jie Liu
As a noninvasive therapy, high-intensity focused ultrasound (HIFU) shows great potential in inducing anticancer immune responses. However, the overall anticancer efficacy of HIFU is still limited due to the rapid attenuation of ultrasound waves and inadequacy of ultrasound waves to spread to the whole tumor. Here, we combined HIFU with the ultrasound contrast agent/chemotherapeutic drug co-delivery nanodroplets to achieve synergistic enhancement of anticancer efficacy. Different from the widely used thermal HIFU irradiation, by which excessive heating would result in inactivation of immune stimulatory molecules, we used short acoustic pulses to trigger HIFU (mechanical HIFU, mHIFU) to improve anticancer immune responses. The nanodroplets displayed a mHIFU/glutathione (GSH)-dual responsive drug release property, and their cellular uptake efficacy and toxicity against cancer cells increased upon mHIFU irradiation. The generated immunogenic debris successfully induced the exposure of damage-associated molecular patterns on the cell surface for dendritic cells (DCs) maturation. In vivo experiments with tumor-bearing mice showed that the co-delivery nanodroplets in combination with mHIFU could effectively inhibit tumor growth by inducing immunogenic cell death, activating DCs maturation, and enhancing the effector T-cell infiltration within tumors. This work reveals that combined treatment with nanodroplets and mHIFU is a promising approach to eradicate tumors.
研究领域:
肿瘤学
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生物医学工程
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免疫治疗
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yinglin Zhou,Xinchang Huang,Tong Su,Kunli Su,Song Peng,Huanan Li
High-intensity focused ultrasound (HIFU) has emerged as one of the preferred modalities for breast-conserving oncotherapy, and immune response it triggers is key to prognosis. Nevertheless, its immunotherapy efficacy is often compromised by the postoperative tumor microenvironment (TME) featured by severe hypoxia and lactate accumulation, leading to subsequent tumor recurrence and metastasis. In this work, we designed hypoxia-specific metal-organic frameworks (AMCMOFs) that co-deliver the hypoxia-activated prodrug AQ4N and CaCO 3 , aiming to enhance tumor immunogenicity and reversing immunosuppression brought by severe hypoxia and elevated lactate in the TME after HIFU surgery. AMCMOFs utilize hypoxia aggravated by HIFU to activate AQ4N, ultimately inducing immunogenic cell death. Meanwhile, CaCO 3 neutralizes intratumoral lactate, reprogramming tumor-associated macrophages from immunosuppressive M2 phenotype toward pro-inflammatory M1 phenotype. Furthermore, the co-release of calcium and manganese ions trigger pyroptosis via mitochondrial ion overload and activate calcium-dependent NFAT pathway of T cells. As a result, AMCMOFs elicit the strong immune response and successfully induce long-lasting immune memory, effectively inhibiting tumor recurrence and metastasis. Therefore, the developed MOFs-based nanoplatform can combine the utilization and regulation of TME, offering a compelling strategy for improving the prognosis of all surgical operations, including HIFU, in oncotherapy.
研究领域:
肿瘤学
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免疫治疗
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纳米医学
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肿瘤微环境
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代谢重编程
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生物无机化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Yu Tang,Chun Chen,Binglei Jiang,Lu Wang,Fujie Jiang,Disen Wang,Yaotai Wang,Haiyan Yang,Xia Ou,Yan Du,Qi Wang,Jianzhong Zou
Purpose Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for Bifidobacterium bifidum (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer.Methods We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF in vivo. Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor.Results The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chemotherapy, this therapy not only inhibits tumor growth, but also significantly prolongs the survival time of mice. More importantly, this treatment strategy has no obvious side effects.Conclusion We successfully established a novel therapy method, BF-mediated HIFU ablation, which provides an excellent platform for highly efficient and non-invasive therapy of tumor.
研究领域:
癌症治疗
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纳米医学
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微生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6067
·
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
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Zhezhu Nan,Linrong Shi,Hengyu Liu,Xinyue Han,Junjie Chen,Daocheng Wu,Mingxi Wan,Yi Feng
High-intensity focused ultrasound (HIFU) has been employed in clinical practice for tumor treatment via thermal ablation. However, the high energy requirements of HIFU raise safety concerns, and insufficient therapeutic efficacy can lead to potential tumor recurrence. To address these issues, we developed multifunctional theranostic nanoparticles (PFP@POMP@MnO2–Ce6 NPs) and utilized dual-frequency HIFU technology to enhance therapeutic efficiency at lower energy levels. This approach achieved efficient and rapid thermal/cavitation/sonodynamic synergistic therapy, leveraging long-term therapy through immune responses and precise monitoring via US/MRI dual-modal imaging. The NPs are composed of polymer micelles that encapsulate perfluoropentane (PFP), with their surface modified by MnO2 and sonosensitizer Chlorin e6 (Ce6). The results indicated that dual-frequency HIFU irradiation triggered the vaporization of PFP within the NPs, enhancing both the thermal and cavitation effects of HIFU, which led to an increase in the area of thermal damage in the phantoms. In vitro and in vivo experiments demonstrated that the NPs, when combined with dual-frequency HIFU, could achieve synergistic antitumor effects, inducing 94.1 ± 1.5% (p < 0.01) tumor cell death in vitro and ablation of directly treated tumors without recurrence in vivo. Most interestingly, the synergistic therapy suppressed the growth of distal tumors (93.4 ± 1.1% growth inhibition), indicating enhanced immune responses, which was further supported by immunohistochemical (IHC) results of a 69.3 ± 1.5% increase in CD8+ T cell infiltration and a 61.2 ± 1.5% increase in F4/80+ macrophage infiltration. It ensured the longevity of the treatment effects and reduced the likelihood of tumor recurrence. Moreover, the NPs’ dual-modal imaging (US/MRI) capabilities provided real-time guidance and improved tumor visualization, confirming their utility as potent theranostic agents. This therapeutic approach, facilitated by multifunctional nanoparticles and in synergy with dual-frequency HIFU, provided precise imaging guidance, enhanced therapeutic efficacy, and elicited an immune response, thereby effectively addressing the limitations inherent to traditional HIFU therapy.
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Jingnan Li,Chengyan Luo,Tingyu Sun,Yinglin Zhou,Xinchang Huang,Dezhou Wu,Xirui Luo,Chao Zeng,Huanan Li
As a noninvasive treatment modality, high-intensity focused ultrasound (HIFU)-induced antitumor immune responses play a vital role in surgery prognosis. However, limited response intensity largely hinders postoperative immunotherapy. Herein, a hypoxia-specific metal–organic framework (MOF) nanosystem, coordinated by Fe3+, hypoxic-activated prodrug AQ4N, and IDO-1 signaling pathway inhibitor NLG919, is developed for the potentiating immunotherapy of HIFU surgery. The loaded AQ4N enhances the photoacoustic imaging effects to achieve accurate intraoperative navigation. Within the HIFU-established severe hypoxic environment, AQ4N is activated sequentially, following which it cooperates with Fe3+ to effectively provoke immunogenic cell death. In addition, potent NLG919 suppresses IDO-1 activity and degrades the immunosuppressive tumor microenvironment aggravated by postoperative hypoxia. In vivo studies demonstrate that the MOF-mediated immunotherapy greatly inhibits the growth of primary/distant tumors and eliminates lung metastasis. This work establishes a robust delivery platform to improve immunotherapy and the overall prognosis of HIFU surgery with high specificity and potency.
研究领域:
肿瘤学
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生物医学工程
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诊疗学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2021
·
IF 11.614
Xinping Kuai,Yuefei Zhu,Zheng Yuan,Shengyu Wang,Lin Lin,Xiaodan Ye,Yiping Lu,Yu Luo,Zhiqing Pang,Daoying Geng,Bo Yin
Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO 2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8 + and CD4 + T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.
研究领域:
癌症治疗
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纳米技术
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医学成像
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免疫学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Disen Wang,Fujie Jiang,Lu Wang,Yu Tang,Zhong Zhang,Yan Du,Jianzhong Zou
The acoustic propagation characteristic of ultrasound determines that the energy of ultrasound beam will decrease with the increase of its propagation depth in the body. Similarly, the energy of High Intensity Focused Ultrasound (HIFU) will be attenuated with the increase of HIFU propagation depth in the body. Ensuring sufficient ultrasound energy deposition in the HIFU ablation region for tumor ablation is usually achieved by increasing the ultrasound irradiation power or prolonging the ultrasound ablation time. However, these two methods may damage the normal tissue adjacent to the HIFU ablation region. Herein, we constructed the nanoparticles conjugated with tumor-homing bacteria as the biological tumor-homing synergist to facilitate HIFU-mediated tumor ablation avoiding the potential safety risk. In our strategy, Bifidobacterium bifidum ( B. bifidum ) was selectively colonized in the hypoxic region of solid tumors after been injected into 4T1 breast cancer bearing-BALB/c mice via the tail vein due to its anaerobic growth characteristic. The amount of B. bifidum with negative surface potential in the hypoxic region of solid tumors was increased by its anaerobic proliferation. Polyethylenimine (PEI) -modified Poly (lactic- co -glycolic) acid nanoparticles loaded sodium bicarbonate (PEI-PLGA-NaHCO 3 -NPs) with positive surface potential injected into 4T1 breast cancer bearing-BALB/c mice via the tail vein displayed the tumor-homing ability by the electrostatic adsorption with B. bifidum colonized solid tumors. PEI-PLGA-NaHCO 3 -NPs could release NaHCO 3 to produce carbon dioxide (CO 2 ) as cavitation nuclei inside the acidic microenvironment of solid tumors. When HIFU irradiated solid tumors contained with more cavitation nuclei, the ultrasound energy deposition at the tumor region was increased to destroy the tumors more effectively. Meanwhile, the improved efficiency of HIFU-mediated tumor ablation reduced the dependence of the tumor ablation on the ultrasound energy dose, which improved the safety of HIFU-mediated tumor ablation to the non-targeted ablation tissue. This tumor-homing synergist shows the potential application value on the HIFU-mediated tumor ablation in the clinical.
研究领域:
肿瘤学
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生物医学工程
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超声治疗
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纳米医学
✓ 已验证
DOI
PubMed
高影响因子
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