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JOURNAL OF NANOBIOTECHNOLOGY · 2025 · IF 12.6

Surface-engineered bio-manufactured gas vesicles for multimodal imaging of glioma

Juanjuan Li,Yutong Cui,Xiaoli Jiang,Xue Chi,Hong Li,Xiang Ma,Yanqiong Tang,Denggao Huang,Zhu Liu

Integrated imaging techniques offer enhanced medical insights into the central nervous system by combining different modalities. In glioma diagnosis, the challenge often lies in delivering contrast agents effectively across the blood-brain barrier. We present an integrated multimodal imaging biohybrid, GV@pCY5, which enables blood-brain barrier penetrating as well as fluorescence and ultrasound (FL/US) imaging capabilities. This biohybrid is created by decorating a far-red-fluorescent cyanine dye (CY5) onto polyethyleneimine (PEI)-coated gas vesicles (GV). The layer-by-layer assembly improves the stability and performance of GV@pCY5 under ultrasound, thanks to the hydration shell variation induced by PEI. Given to the blood-brain barrier penetrating ability, GV@pCY5 demonstrates increase both in fluorescence and ultrasound imaging performance compared to single-component systems, proving effective for glioma diagnosis in vivo. This study underscores the potential of the FL/US platform for dual ratiometric imaging of various cerebral conditions.

CAS / MDL: 9012-36-6 146368-11-8
研究领域: 生物医学工程 · 神经科学 · 分子影像学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nature Communications · 2021 ·Vol. 12 ·期 1 ·1-9 · IF 14.919

Lead halide perovskite for efficient optoacoustic conversion and application toward high-resolution ultrasound imaging

Du Xinyuan,Li Jiapu,Niu Guangda,Yuan Jun-Hui,Xue Kan-Hao,Xia Mengling,Pan Weicheng,Yang Xiaofei,Zhu Benpeng,Tang Jiang

Lead halide perovskites have exhibited excellent performance in solar cells, LEDs and detectors. Thermal properties of perovskites, such as heat capacity and thermal conductivity, have rarely been studied and corresponding devices have barely been explored. Considering the high absorption coefficient (10 4 ~10 5  cm −1 ), low specific heat capacity (296–326 J kg −1 K −1 ) and small thermal diffusion coefficient (0.145 mm 2 s −1 ), herein we showcase the successful use of perovskite in optoacoustic transducers. The theoretically calculated phonon spectrum shows that the overlap of optical phonons and acoustic phonons leads to the up-conversion of acoustic phonons, and thus results in experimentally measured low thermal diffusion coefficient. The assembled device of PDMS/MAPbI 3 /PDMS simultaneously achieves broad bandwidths (−6 dB bandwidth: 40.8 MHz; central frequency: 29.2 MHz), and high conversion efficiency (2.97 × 10 −2 ), while all these parameters are the record values for optoacoustic transducers. We also fabricate miniatured devices by assembling perovskite film onto fibers, and clearly resolve the fine structure of fisheyes, which demonstrates the strong competitiveness of perovskite based optoacoustic transducers for ultrasound imaging.

研究领域: 材料科学 · 医学影像 · 光学
✓ 已验证 DOI PubMed 高影响因子
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

n-Butanol Enables OMVs as Heat-Responsive Nanometer Ultrasound Contrast Agents for Tumor Imaging

Lujiao Wang,Song Yang,Tao Zhou,Siyu Yang,Pengyu Bi,Jiangyi Zhou,Qi Wang,Hai Qiao

Extracellular vesicles, such as Escherichia coli outer membrane vesicles (OMVs), have been widely explored as carriers for contrast agents, yet their application in ultrasound imaging remains limited. In this study, heat-responsive nB-OMVs are developed by loading n-butanol into OMVs (nB-OMVs). Upon heating, the decreased solubility of n-butanol triggered phase separation within the vesicles, resulting in enhanced ultrasound signals, including fundamental, harmonic, and subharmonic components. Experimental results demonstrated that nB-OMVs retained the native morphology of OMVs, along with their tumor-targeting accumulation and tumor growth inhibition capabilities. nB-OMVs injection induces red blood cell extravasation into tumors, under near-infrared (NIR) irradiation, these extravasated RBCs acted as photothermal mediators, generating a localized thermal environment that activated intratumoral nB-OMVs and further amplified the ultrasound signal. In B-mode and contrast-enhanced ultrasound (CEUS) imaging, tumor grayscale intensities increased by 4.6- and 8.5-fold, respectively. This work provides a promising strategy for ultrasound-based tumor imaging using extracellular vesicles.

研究领域: 医学影像学 · 生物材料学 · 肿瘤学
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Journal of Materials Chemistry B · 2017 ·Vol. 5 ·期 29 ·5845-5853 · IF 4.543

Preparation and evaluation of glycyrrhetinic acid-modified and honokiol-loaded acoustic nanodroplets for targeted tumor imaging and therapy with low-boiling-point phase-change perfluorocarbon

Ping Zhang,Yang Cao,Huali Chen,Bo Zhou,Wenjing Hu,Liangke Zhang

In this study, a multi-functional drug delivery system, which combines targeted tumor treatment with glycyrrhetinic acid-modified nanodroplets and ultrasound imaging with low-boiling-point phase-change perfluorocarbon, was proposed and validated. The obtained nanodroplets were spherical in shape with an average size of 324.8 ± 183.7 nm and a negative zeta-potential. Low-intensity focused ultrasound (LIFU) was introduced to perform targeted US imaging via acoustic droplet vaporization (ADV) both in vitro and in vivo. The in vitro cytotoxicity and cellular uptake studies conducted on HepG2 cells demonstrated that nanodroplets modified with glycyrrhetinic acid enhanced the selective delivery to cells expressing high levels of glycyrrhetinic acid receptors. Moreover, the glycyrrhetinic acid-modified nanodroplets showed significant antitumor efficacy in HepG2 cell-bearing mice with the assistance of both passive targeting via the EPR effects and active targeting ability of glycyrrhetinic acid. In conclusion, our fabricated multi-functional nanodroplets possess targeted antitumor activity and simultaneous US imaging, providing high potential for targeted tumor theranostics.

研究领域: 药剂学 · 肿瘤学 · 医学影像学
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International Journal of Nanomedicine · 2021 · IF 6.4

A Highly Efficient One-for-All Nanodroplet for Ultrasound Imaging-Guided and Cavitation-Enhanced Photothermal Therapy

Dui Qin,Lei Zhang,Hongrui Zhu,Junjie Chen,Daocheng Wu,Ayache Bouakaz,Mingxi Wan,Yi Feng

Background Photothermal therapy (PTT) has attracted considerable attention for cancer treatment as it is highly controllable and minimally invasive. Various multifunctional nanosystems have been fabricated in an “all-in-one” form to guide and enhance PTT by integrating imaging and therapeutic functions. However, the complex fabrication of nanosystems and their high cost limit its clinical translation.Materials and Methods Herein, a high efficient “one-for-all” nanodroplet with a simple composition but owning multiple capabilities was developed to achieve ultrasound (US) imaging-guided and cavitation-enhanced PTT. Perfluoropentane (PFP) nanodroplet with a polypyrrole (PPy) shell (PFP@PPy nanodroplet) was synthesized via ultrasonic emulsification and in situ oxidative polymerization. After characterization of the morphology, its photothermal effect, phase transition performance, as well as its capabilities of enhancing US imaging and acoustic cavitation were examined. Moreover, the antitumor efficacy of the combined therapy with PTT and acoustic cavitation via the PFP@PPy nanodroplets was studied both in vitro and in vivo.Results The nanodroplets exhibited good stability, high biocompatibility, broad optical absorption over the visible and near-infrared (NIR) range, excellent photothermal conversion with an efficiency of 60.1% and activatable liquid-gas phase transition performance. Upon NIR laser and US irradiation, the phase transition of PFP cores into microbubbles significantly enhanced US imaging and acoustic cavitation both in vitro and in vivo. More importantly, the acoustic cavitation enhanced significantly the antitumor efficacy of PTT as compared to PTT alone thanks to the cavitation-mediated cell destruction, which demonstrated a substantial increase in cell detachment, 81.1% cell death in vitro and 99.5% tumor inhibition in vivo.Conclusion The PFP@PPy nanodroplet as a “one-for-all” theranostic agent achieved highly efficient US imaging-guided and cavitation-enhanced cancer therapy, and has considerable potential to provide cancer theranostics in the future.

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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Scientific Reports · 2013 ·Vol. 3 ·期 1 ·1-8 · IF 2.927

Polypyrrole Hollow Microspheres as Echogenic Photothermal Agent for Ultrasound Imaging Guided Tumor Ablation

Zha Zhengbao,Wang Jinrui,Qu Enze,Zhang Shuhai,Jin Yushen,Wang Shumin,Dai Zhifei

Ultrasound (US) imaging provides a valuable opportunity to administer photothermal therapy (PTT) of cancer with real-time guidance to ensure proper targeting, but only a few theranostic agents were developed by physically grafting near infrared (NIR)-absorbing inorganic nanomaterials to ready-made ultrasound contrast agents (UCAs) for US imaging guided PTT. In this paper, NIR absorbing hollow microspheres were generated from polypyrrole merely using a facile one-step microemulsion method. It was found that the obtained polypyrrole hollow microspheres (PPyHMs) can act as an efficient theranostic agent not only to enhance US imaging greatly, but also exhibit excellent photohyperthermic effects. The contrast consistently sustained the echo signals for no less than 5 min and the NIR laser light ablated the tumor completely within two weeks in the presence of PPyHMs. More importantly, no use of additional NIR absorber substantially minimizes an onetime dose of the theranostic agent.

研究领域: 生物医学工程 · 癌症治疗
✓ 已验证 DOI PubMed 高影响因子
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International Journal of Nanomedicine · 2024 · IF 6.6

Preparation of Hematoporphyrin-Poly(Lactic Acid) Nanoparticles Encapsulated Perfluoropentane/Salicylic Acid for Enhanced US/CEST MR Bimodal Imaging

Liqiong Ding,Fengnan Xu,Binhua Luo,Liyuan Cheng,Lingping Huang,Yanlong Jia,Jieqiong Ding

Background Medical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, have gained widespread acceptance in clinical practice for tumor diagnosis. Each imaging modality has its own unique principles, advantages, and limitations, thus necessitating a multimodal approach for a comprehensive disease understanding of the disease process. To enhance diagnostic precision, physicians frequently integrate data from multiple imaging modalities, driving research advancements in multimodal imaging technology research.Methods In this study, hematoporphyrin-poly (lactic acid) (HP-PLLA) polymer was prepared via ring-opening polymerization and thoroughly characterized using FT-IR, 1H-NMR, XRD, and TGA. HP-PLLA based nanoparticles encapsulating perfluoropentane (PFP) and salicylic acid were prepared via emulsion-solvent evaporation. Zeta potential and mean diameter were assessed using DLS and TEM. Biocompatibility was evaluated via cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed with a dedicated apparatus, while CEST MRI was conducted using a 7.0 T animal scanner.Results We designed and prepared a novel dual-mode nanoimaging probe SA/PFP@HP-PLLA NPs. PFP enhanced US imaging, while salicylic acid bolstered CEST imaging. With an average size of 74.43 ± 1.12 nm, a polydispersity index of 0.175 ± 0.015, and a surface zeta potential of −64.1 ± 2.11 mV. These NPs exhibit excellent biocompatibility and stability. Both in vitro and in vivo experiments confirmed the SA/PFP@HP-PLLA NP’s ability to improve tumor characterization and diagnostic precision.Conclusion The SA/PFP@HP-PLLA NPs demonstrate promising dual-modality imaging capabilities, indicating their potential for preclinical and clinical use as a contrast agent.

CAS / MDL: 7722-84-1 301-10-0
研究领域: 医学影像学 · 纳米医学 · 生物材料学
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JOURNAL OF ULTRASOUND IN MEDICINE · 2024 · IF 2.1

Interaction Between Microbubbles and Microwave Ablation

Xinyu Zhong,Xinghao Zhang,Yuting Cao,Ping Zhou

Objectives This study aimed to explore the interactions between microbubbles and microwave ablation (MWA). Methods The study employed custom-made phantoms (in vitro) and white New Zealand rabbits (in vivo). MWA was performed with or without microbubbles in the phantoms (2 × 10 5 particles mL −1 ) and rabbit livers (intravenous injection of 0.05 mL/kg SonoVue). During the MWA, K-type thermocouple probes were used to monitor the MWA-induced temperature increase. Contrast-enhanced ultrasound imaging (CEUS) was used to monitor and analyze the microbubbles signal intensity. After MWA, the ablation-zone volumes were evaluated and compared between the groups with and without microbubbles. Results In both the phantom models and rabbits, microbubbles showed no significant influence on MWA, including the ablation range and MWA-induced temperature increase. In phantoms and rabbit livers filled with microbubbles, MWA caused the formation of a gradually expanding microbubble-defect region over the ablation time. An increase in the temperature caused microbubble destruction. Conclusions Microbubbles had no significant influence on MWA. However, MWA induced the destruction of microbubbles in a temperature-dependent manner. Thus, the poor thermotolerance of microbubbles is a non-negligible barrier when using CEUS to monitor the ablation range during MWA in real-time.

研究领域: 医学影像学 · 肿瘤学
✓ 已验证 DOI PubMed 高影响因子
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BIOMATERIALS · 2013 · IF 7.604

Engineering of perfluorooctylbromide polypyrrole nano-/microcapsules for simultaneous contrast enhanced ultrasound imaging and photothermal treatment of cancer

Zhengbao Zha,Jinrui Wang,Shuhai Zhang,Shumin Wang,Enze Qu,Youyi Zhang,Zhifei Dai

A versatile oil-in-water emulsion method has been explored for constructing water-dispersible polypyrrole (PPy) nano-/microcapsules with a soluble PPy complex as multifunctional photothermal agents for tumor ablation. In this work, both PPy nanocapsules (280.4 ± 79.0 nm) and microcapsules (1.31 ± 0.45 μm) with liquid perfluorooctylbromide (PFOB) core could be obtained by simply tuning the process energy for emulsion formation from ultrasonication to homogenization . Owing to the encapsulated liquid PFOB and strong near-infrared (NIR) absorption of PPy shell, the resulted PPy capsules showed great promise in ultrasound imaging guided photothermal ablation of tumor cells without inducing any significant side effect. Thus, it is anticipated that fine-tuning of the other encapsulated drugs or functional materials in PPy capsules would foster avenues for the development of multifunctional platforms for cancer treatments.

研究领域: 生物医学工程 · 肿瘤学 · 材料科学
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Applied Materials Today · 2021 · IF 10.041

Multi-response biocompatible Janus micromotor for ultrasonic imaging contrast enhancement

Yiwen Feng,Xiaocong Chang,Hao Liu,Ying Hu,Tianlong Li,Longqiu Li

The acid-base environment of the biological digestive system is formed with the help of hydrogen ions and bicarbonate. At the same time, the chloride capacity in the blood is not ignorable. These ionic environments provide a new horizon for the medical application of bubble-propelled micromotors. Herein, a Janus Mg-based micromotor is reported as a novel ultrasonic contrast agent and its potential advantages in medical imaging are explored. With the capability of being powered by the magnetic field, these micromotors could be navigated to the corresponding ionic environment, and then they would rapidly generate continuous bubbles. These bubbles achieve an efficient and guided propulsion of micromotor, also provide support for contrast-enhanced ultrasound imaging. Besides owning the dual functions of imaging and targeted transport, the micromotors present aggregation response under the action of ultrasound, which is helpful for local reinforcement of the imaging effect. Such multi-response biocompatible Janus micromotor provides a new perspective for medical imaging and diagnosis.

研究领域: 医学影像学 · 生物医学工程
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ACS Applied Materials & Interfaces · 2019 · IF 8.456

Lipid/PLGA Hybrid Microbubbles as a Versatile Platform for Noninvasive Image-Guided Targeted Drug Delivery

Yan Chen,Yangbiao Liang,Peng Jiang,Fei Li,Bo Yu,Fei Yan

Microbubbles (MBs) have recently emerged as promising theranostic carriers for ultrasound contrast imaging and drug delivery. However, conventional lipid-based MBs have a poor drug encapsulation efficiency, and polymer-based MBs show a weak capability in contrast imaging and ultrasound-triggered drug release. Here, we developed a novel type of multiporous lipid/PLGA hybrid MBs (lipid/PLGA MBs) that solved the dilemma of MBs as imaging agents and drug carriers. The lipid/PLGA MBs were designed through regulating the elasticity of the bubble shells using lipids to incorporate into the PLGA shells and ammonium bicarbonate as a gas-generating agent. The softened shells and the porous bubble structure make them be able to generate stronger harmonic signals and be more vulnerable to ultrasound irradiation, leading to their excellent performance in ultrasound contrast imaging and ultrasound-triggered MB destruction in vitro and in vivo. By using doxorubicin (Dox) as a model drug, the Dox-loaded lipid/PLGA MBs (Dox-lipid/PLGA MBs) were prepared and achieved a high drug encapsulation efficiency. The real-time tracking of drug delivery and on-command controlled drug release by ultrasound were successfully realized in the tumor-bearing mice. A significantly enhanced tumor growth inhibition effect could be observed when using Dox-lipid/PLGA MBs combined with ultrasound irradiation, compared with free Dox and Dox-lipid/PLGA MBs without ultrasound. Our study provides an innovative multifunctional platform of MBs for ultrasound contrast imaging and drug delivery applications.

CAS / MDL: 9002-89-5
研究领域: 医学影像学 · 药剂学 · 生物医学工程
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2021 · IF 5.875

Contrast-enhanced ultrasound imaging using long-circulating cationic magnetic microbubbles in vitro and in vivo validations

Yingying Liu,Xiaoshu Lai,Yao Zhu,Fengjuan Guo,Lili Su,Gulzira Arkin,Tianzhen He,Jinfeng Xu,Haitao Ran

Traditional encapsulated microbubbles are recently used as delivery carriers for drugs and genes, but they have low efficiency. If the local microbubble concentration could be increased, this might be able to improve the therapeutic efficacy of diseases. In this study, we developed novel cationic magnetic microbubbles (MB M ), which could simultaneously realize targeted aggregation under a magnetic field as well as ultrasonographic real-time visualization. Their physicochemical properties, biocompatibility , ultrasonography, magnetic response characteristics, and biodistribution were systematically evaluated. Here, the MB M were 2.55 ± 0.14 µm in size with a positive zeta potential , and had a good biocompatibility. They were able to enhance ultrasonographic contrast both in vitro and in vivo. MB M could be attracted by an external magnet for directional movement and aggregation in vitro. We confirmed that MB M also had a great magnetic response in vivo, by means of fluorescence imaging and contrast-enhanced ultrasound imaging. Following intravenous injection into tumor-bearing mice, MB M showed excellent stability in the internal circulation, and could accumulate in the tumor vasculature through magnetic targeting. With the excellent combination of magnetic response and acoustic properties, cationic magnetic microbubbles (MB M ) have promising potential for use as a new kind of drug/gene carrier for theranostics in the future.

研究领域: 医学影像学 · 生物医学工程 · 纳米医学
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