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Advances in microbubble-assisted ultrasound-guided gene therapy:Mechanisms and applications

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Science China Materials 2024年第9期67卷 2749-2766页

作者： Zhen Tie Shuhao Zhang Yunfeng Qu Mengxuan Wang Renfa Liu Desheng Sun zhifei dai Department of Biomedical Engineering College of Future TechnologyNational Biomedical Imaging CenterState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100871China Department of Ultrasonic Imaging Peking University Shenzhen HospitalShenzhen 518035China

Gene therapy,as one of the popular therapies nowadays,has been applied with great success in various ***,there are also concerns about the safety,therapeutic efficacy,and applicability of gene ***crobubble-assisted ultrasound-guided gene therapy offers the following incomparable advantages over conventional meth***,this strategy enables the therapeutic nucleic acids to effectively cross the barriers like cell membrane,blood-brain barrier,and blood-retinal barrier that exist in the body and reach regions that cannot be accessed by conventional methods,which extends the scope of applications of gene ***,it is possible to restrict the zone of gene transfection to the lesion area by controlling the irradiation coverage of ultrasound,hence effectively controlling the risk of ***,with the support of various imaging techniques like ultrasound imaging and magnetic resonance imaging,the procedure of gene therapy can be under image guidance,which will dramatically improve the safety of gene *** review will highlight on the advances in ultrasound-enhanced gene delivery strategy,attention to the relevant mechanisms of the strategy,the derived technologies and the related cutting-edge ***,we will also have a discussion on the limitations and future prospects associated with this gene delivery strategy.

关键词： gene therapy microbubble ultrasound cavitation image-guided gene therapy

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光敏剂的转化与创新

中国激光 2024年第9期51卷 114-130页

作者：刘开宁李睿刘仁发戴志飞北京大学未来技术学院生物医学工程系北京100871 南开大学生命科学学院天津300071

以光敏剂为基础的光动力疗法已被确定为许多肿瘤、皮肤性疾病、血管性疾病等适应证的安全治疗方式。在近些年的研究中,卟啉类光敏剂、二氢卟吩类光敏剂等均投入临床使用,酞菁类光敏剂、稠环醌类光敏剂等均已开展临床研究。但是,光动力... 详细信息

以光敏剂为基础的光动力疗法已被确定为许多肿瘤、皮肤性疾病、血管性疾病等适应证的安全治疗方式。在近些年的研究中,卟啉类光敏剂、二氢卟吩类光敏剂等均投入临床使用,酞菁类光敏剂、稠环醌类光敏剂等均已开展临床研究。但是,光动力疗法在临床转化中还面临着诸多问题,如有限的穿透深度、较低的溶解度、暗毒性、对氧气浓度的高度依赖等,新型的安全高效的光敏剂亟待被进一步开发,以实现高度特异性微创治疗。目前,新型光敏剂的研发主要聚焦于靶向修饰和智能纳米药物递送体系以及可激活/响应型光敏剂、耐乏氧肿瘤微环境的Ⅰ型光敏剂、适应深层实体瘤治疗的光敏剂等。此外,超声激发的声动力治疗也为光敏剂的临床应用开辟了新思路。随着新型光敏剂的开发与转化,将会有更多的光敏剂药物被应用于临床实践,为癌症和其他疾病患者带来福音。

关键词：医用光学光敏剂光动力疗法临床应用

Nanotherapeutic approaches targeting angiogenesis and immune dysfunction in tumor microenvironment

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Science China(Life Sciences) 2018年第4期61卷 380-391页

作者： Sadaf Hameed Pravin Bhattarai zhifei dai Department of Biomedical Engineering College of Engineering Peking University

Tumor microenvironment （TME） comprising cellular and non-cellular components is a major source of cancer hallmarks. Notably, angiogenesis responsible for normal physiological remodeling process can otherwise harness vessel abnormalities during tumorigenesis eliciting severe therapeutic inefficiency. Currently, FDA approved antiangiogenic drugs have only shown modest clinical success owing to tumor hypoxia, antiangiogenic therapeutic resistance, and limited knowledge in understanding TME. In order to overcome these limitations, targeting angiogenesis combined with immtmosuppressive TME could offer potential therapeutic opportunities. Indeed, these therapeutic approaches can be further revisited with the advent of nano- technology that can target the key cellular components of TME and tumor cells more precisely. Synergetic targeting without eliciting systemic toxicity achieved by integration of antiangiogenic and immunotherapy in a single nanoplatform is vital for therapeutic success. In this review, we will discuss the most promising nanotechnological advancements oriented to modulate the immunosuppressive TME in association with antiangiogenic therapy that has gained immense popularity in cancer treatment.

关键词： tumor microenvironment nanoparticles angiogenesis immunosuppression

Nanotechnology assisted photo-and sonodynamic therapy for overcoming drug resistance

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Cancer Biology & Medicine 2021年第2期18卷 388-400页

作者： Rui Li Zhimin Chen zhifei dai Yingjie Yu College of Life Science and Technology Beijing University of Chemical TechnologyBeijing 100029China Department of Biomedical Engineering College of EngineeringPeking UniversityBeijing 100871China Institute of Translational Medicine The First Affiliated Hospital of Shenzhen UniversityShenzhen Second People’s HospitalShenzhen 518039China

Drug resistance is considered the most important reason for the clinical failure of cancer *** drug resistance and improving the efficacy of anticancer agents remains a major *** the past several decades,photodynamic therapy(PDT)and sonodynamic therapy(SDT)have attracted substantial attention for their efficacy in cancer treatment,and have been combined with chemotherapy to overcome drug ***,simultaneously delivering sensitizers and chemotherapy drugs to same tumor cell remains challenging,thus greatly limiting this combinational *** rapid development of nanotechnology provides a new approach to solve this ***-based drug delivery systems can not only improve the targeted delivery of agents but also co-deliver multiple drug components in single nanoparticles to achieve optimal synergistic *** this review,we briefly summarize the mechanisms of drug resistance,discuss the advantages and disadvantages of PDT and SDT in reversing drug resistance,and describe state-of-the-art research using nano-mediated PDT and SDT to solve these refractory *** review also highlights the clinical translational potential for this combinational therapy.

关键词： Drug resistance photodynamic therapy sonodynamic therapy chemotherapy nanotechnology

Photosensitizer Nanoparticles Boost Photodynamic Therapy for Pancreatic Cancer Treatment

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Nano-Micro Letters 2021年第2期13卷 246-261页

作者： Huanyu Yang Renfa Liu Yunxue Xu Linxue Qian zhifei dai Department of Ultrasound Beijing Friendship HospitalCapital Medical UniversityNo.95 Yongan RoadXicheng DistrictBeijing 100050People’s Republic of China Department of Biomedical Engineering College of EngineeringPeking UniversityNo.5 Yiheyuan RoadHaidian DistrictBeijing 100871People’s Republic of China

Patients with pancreatic cancer(PCa)have a poor prognosis apart from the few suitable for *** therapy(PDT)is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in ***,it suffers from certain limitations during clinical exploitation,including insufficient photosensitizers(PSs)delivery,tumor-oxygenation dependency,and treatment escape of aggressive *** overcome these obstacles,an increasing number of researchers are currently on a quest to develop photosensitizer nanoparticles(NPs)by the use of a variety of nanocarrier systems to improve cellular uptake and biodistribution of *** of PSs with NPs endows them significantly higher accumulation within PCa tumors due to the increased solubility and stability in blood circulation.A number of approaches have been explored to produce NPs co-delivering multi-agents affording PDT-based synergistic therapies for improved response rates and durability of response after *** review provides an overview of available data regarding the design,methodology,and oncological outcome of the innovative NPs-based PDT of PCa.

关键词： Photodynamic therapy Photosensitizer Nanoparticle Pancreatic cancer Combined therapy

Fibronectin-targeted dual-acting micelles for combination therapy of metastatic breast cancer

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2384-2394页

作者： Zhuoran Gong Min Chen Qiushi Ren Xiuli Yue zhifei dai Department of Biomedical Engineering College of EngineeringPeking UniversityBeijing 100871China School of Environment Harbin Institute of TechnologyHarbin 150090China

Stage IV breast cancer,which has a high risk of invasion,often develops into metastases in distant organs,especially in the lung,and this could threaten the lives of ***,the development of more advanced therapeutics that can efficiently target metastatic foci is *** this study,we built an dual-acting therapeutic strategy using micelles with high stability functionalized with fibronectin-targeting CREKA peptides encapsulating two slightly soluble chemotherapy agents in water,doxorubicin(D)and vinorelbine(V),which we termed *** found that small C-DVM micelles could efficiently codeliver drugs into 4T1 cells and disrupt microtubule structures.C-DVM also exhibited a powerful ability to eradicate and inhibit invasion of 4T1 ***,an in vivo pharmacokinetics study showed that C-DVM increased the drug circulation half-life and led to increased enrichment of drugs in lung metastatic foci after 24 ***,dual-acting C-DVM treatment led to 90%inhibition of metastatic foci development and reduced invasion of metastases.C-DVM could potentially be used as a targeted treatment for metastasis and represents a new approach with higher therapeutic efficacy than conventional chemotherapy for stage IV breast cancer that could be used in the future.

关键词： drugs chemotherapy organs

Current trends and key considerations in the clinical translation of targeted fluorescent probes for intraoperative navigation

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Aggregate

Aggregate 2021年第3期2卷 54-76页

作者： Renfa Liu Yunxue Xu Kun Xu zhifei dai Department of Biomedical Engineering College of EngineeringPeking UniversityBeijingChina

The rapid development of fluorescence imaging for intraoperative navigation has spurred further development of targeted fluorescent probes in the past *** a few nontargeted dyes,including indocyanine green and methylene blue,are currently applied for fluorescence guided surgery in the *** no targeted fluorescent probes have been approved for the clinic,a number of them have entered clinical *** probes have emission wavelengths in the visible and near infrared(NIR)-I(700-900 nm)*** them,activatable probes and nanoprobes have generated special *** with NIR-I fluorescent probes,NIR-II(1000-1700 nm)fluorescent probes exhibit better intravital performance in terms of increased penetration depths,reduced tissue autofluorescence,and higher signalto-background ***,more challenges are expected before the successful translation of NIR-II probes from bench to *** review provides a brief overview of targeted fluorescent probes under clinical evaluation and recent achievements in the field of NIR-II fluorescence *** addition,we outline key considerations concerning the design of fluorescent probes for clinical translation.

关键词： clinical translation fluorescence imaging intraoperative navigation targeted fluorescent probes tumor surgery

Cyanine conjugates in cancer theranostics

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Bioactive Materials 2021年第3期6卷 794-809页

作者： Yang Li Yiming Zhou Xiuli Yue zhifei dai Department of Biomedical Engineering College of EngineeringPeking UniversityBeijing 100871China School of Environment Harbin Institute of TechnologyHarbin 150001China

Cyanine is a meritorious fluorogenic core for the construction of fluorescent probes and its phototherapeutic potential has been enthusiastically explored as ***,the covalent conjugation of cyanine with other potent therapeutic agents not only boosts its therapeutic efficacy but also broadens its therapeutic ***,we summarize miscellaneous cyanine-therapeutic agent conjugates in cancer theranostics from literature published between 2014 and *** application scenarios of such theranostic cyanine conjugates covered common cancer therapeutic modalities,including chemotherapy,phototherapy and targeted ***,cyanine conjugates that serve as nanocarriers for drug delivery are introduced as *** an additional section,we analyze the potential of these conjugates for clinical ***,this review is aimed to stimulate research interest in exploring unattempted therapeutic agents and novel conjugation strategies and hopefully,accelerate clinical translation in this field.

关键词： Cyanine conjugate Cancer theranostics Therapeutic agent Nanocarrier Clinical translation

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手术导航用荧光探针

化学进展 2021年第1期33卷 52-65页

作者：徐云雪刘仁发徐坤戴志飞北京大学工学院生物医学工程系北京100871 北京大学前沿交叉学科研究院北京100871

荧光成像技术因具有操作简便、分辨率高、安全性好且可实时成像等优势,在术中导航中具有广阔的应用前景。虽然目前还没有靶向荧光探针在临床上得到批准,但已经有相当一部分荧光探针进入了临床试验阶段。最早进入临床试验的是一些偶联肿... 详细信息

荧光成像技术因具有操作简便、分辨率高、安全性好且可实时成像等优势,在术中导航中具有广阔的应用前景。虽然目前还没有靶向荧光探针在临床上得到批准,但已经有相当一部分荧光探针进入了临床试验阶段。最早进入临床试验的是一些偶联肿瘤靶向配体的荧光染料,例如近红外菁染料(IRDye800CW)标记的肿瘤特异抗体,叶酸标记的异硫氰酸荧光素(EC17)等。近来,结构更复杂的荧光探针如酶反应激活型探针和PET/荧光双模态探针也逐步进入临床试验。本文依据近年来手术导航用荧光探针的最新研究进展,分别就受体介导的靶向荧光探针、可激活型靶向荧光探针、近红外二区(NIR-Ⅱ)荧光探针、多模态荧光探针和诊疗一体化探针进行了分类讨论,重点对正在进行临床研究及具有临床转化前景的荧光探针的分子设计原理进行了分析与总结,并对手术导航用荧光探针未来的发展进行了展望。

关键词：荧光手术导航受体介导的靶向荧光探针可激活型靶向荧光探针 NIR-Ⅱ荧光成像多模态荧光探针诊疗一体化荧光探针临床转化