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Theranostics · 2019 · IF 8.063

Molecular Engineering of Near-Infrared Light-Responsive BODIPY-Based Nanoparticles with Enhanced Photothermal and Photoacoustic Efficiencies for Cancer Theranostics

Duyang Gao,Boyu Zhang,Yubin Liu,Dehong Hu,Zonghai Sheng,Xuanjun Zhang,Zhen Yuan

Background : Engineering a single organic-molecule-based nanoparticle integrating precise diagnosis and effective therapy is of great significance for cancer treatment and future clinical applications but remains a great challenge. The goal of this study is to explore small organic molecule-based nanoparticles with high photothermal conversion efficiency for photoacoustic imaging-guided therapy. Methods : Heptacyclic B, O-chelated BODIPY structure (namely Boca-BODIPY) with strong near-infrared (NIR) absorption was designed as a theranostic agent through simply molecular engineering, in which heavy atoms and alkyl chains were introduced to promote its application for tumor theranostics. The Boca-BODIPY molecules are further encapsulated in reduced bovine serum albumin (BSA) through self-assembly. Results : The BSA-Boca-BODIPY exhibited excellent biocompatibility, extraordinary stability and high photothermal conversion efficiency up to 58.7%. The nanoparticles could dramatically enhance photoacoustic contrast of the tumor region, and the signal-to-noise ratio was increased about 14 times at 10 h post intravenous injection in 4T1 tumor-bearing mice. In addition, the nanoassemblies can efficiently convert laser energy (808 nm, 0.75 w cm -2 , 5min) into hyperthermia for tumor ablation. Under the photoacoustic imaging-guided photothermal therapy (PTT), the 4T1 cancer cells were efficiently killed, no tumor recurrence and PTT-induced toxicity is observed. Conclusions : Molecular engineering is a promising way to design organic-molecule-based nanoparticles for cancer theranostics. Other organic-molecule-based nanoparticles which show great promise for imaging-guided cancer precision therapy can be engineered through this method.

CAS / MDL: 9048-46-8
研究领域: 生物医学工程 · 癌症治疗学 · 分子影像学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ADVANCED FUNCTIONAL MATERIALS · 2020 ·Vol. 31 ·期 10 ·2009314 · IF 16.836

Effective Eradication of Tumors by Enhancing Photoacoustic-Imaging-Guided Combined Photothermal Therapy and Ultrasonic Therapy

Caina Xu,Yanbing Wang,Erlei Wang,Nan Yan,Shu Sheng,Jie Chen,Lin Lin,Zhaopie Guo,Huayu Tian,Xuesi Chen

Exploiting a comprehensive strategy that processes diagnosis and therapeutic functions is desired for eradicating tumors. In this study, two versatile nanoparticles are introduced: one is polyethylene glycol- and polyethyleneimine-modified gold nanorods (mPEG–PEI–AuNRs), and the other is formed by electrostatic interactions between mPEG–PEI and calcium carbonate nanoparticles (mPEG–PEI/CaNPs). These two nanoparticles possess following favorable properties: 1) mPEG–PEI–AuNRs and mPEG–PEI/CaNPs show not only high cell uptake in acidic tumoral pH, but also efficient accumulation in tumors with prolonged circulation. 2) mPEG–PEI/CaNPs can generate carbon dioxide (CO 2 ) bubbles in acidic tumoral environment and the photoacoustic (PA) signals from mPEG–PEI–AuNRs can be enhanced with the generation of CO 2 bubbles. 3) The tumors can be eradicated by combining photothermal therapy (PTT) with ultrasonic therapy (UST) under the near-infrared (NIR) laser and ultrasonic irradiation with the presence of mPEG–PEI–AuNRs and CO 2 bubbles from mPEG–PEI/CaNPs. The detailed evaluation of cellular uptake, photothermal property of mPEG–PEI–AuNRs, CO 2 bubbles’ generation from mPEG–PEI/CaNPs, imaging, and combined PTT and UST are carried out in vitro or in vivo. This work has great potential usage for diagnosis and treatment in the future.

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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Advanced Healthcare Materials · 2023 · IF 10

Intracellular Nitroreductase-Triggered “On” and “Enhanced” Photoacoustic Signals for Sensitive Imaging of Tumor Hypoxia

Xianbao Sun,Lingling Xu,Hai-Dong Xu,Limin Xie,Rui Wang,Zhimou Yang,Wenjun Zhan,Shurong Shen,Gaolin Liang

Current molecular photoacoustic (PA) probes are designed with either stimulus-turned “on” or assembly-enhanced signals to trace biological analytes/events. PA probes based on the nature-derived click reaction between 2-cyano-6-aminobenzothiazole (CBT) and cysteine (Cys) (i.e., CBT-Cys click reaction) possess both “turn-on” and “enhanced” PA signals; and thus, should have higher sensitivity. Nevertheless, such PA probes, particularly those for sensitive imaging of tumor hypoxia, remain scarce. Herein, a PA probe NI-Cys(StBu)-Dap(IR780)-CBT (NI-C-CBT) is rationally designed, which after being internalized by hypoxic tumor cells, is cleaved by nitroreductase under the reduction condition to yield cyclic dimer C-CBT-Dimer to turn the PA signal “ON” and subsequently assembled into nanoparticles C-CBT-NPs with additionally enhanced PA signal (“Enhanced”). NI-C-CBT exhibits 1.7-fold “ON” and 3.2-fold overall “Enhanced” PA signals in vitro. Moreover, it provides 1.9-fold and 2.8-fold overall enhanced PA signals for tumor hypoxia imaging in HeLa cells and HeLa tumor-bearing mice, respectively. This strategy is expected to be widely applied to design more “smart” PA probes for sensitive imaging of important biological events in vivo in near future.

研究领域: 生物医学工程 · 分子影像学 · 肿瘤学
✓ 已验证 DOI PubMed 高影响因子
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MOLECULAR PHARMACEUTICS · 2020 · IF 4.321

Delivery of Platinum(IV) Prodrugs via Bi2Te3 Nanoparticles for Photothermal–Chemotherapy and Photothermal/Photoacoustic Imaging

Yan Ma,Dong-Yang Zhang,Zhuo Peng,Shixia Guan,Junqiu Zhai

Combinational administration of photothermal therapy (PTT) and chemotherapy (CT) shows great potential in improving the efficiency of tumor treatment. Herein, we designed a novel nanocomposite Pt@Bi2Te3 composed of bismuth telluride (Bi2Te3) nanoparticles and platinum(IV) prodrugs (Pt) for PTT–CT combination therapy. The obtained Bi2Te3 was synthesized by a simple solvothermal method and modified by polyethylene glycol, which exhibited excellent photothermal (PT) efficiency and stability and could also serve as a bimodal bioimaging contrast agent in PT and photoacoustic (PA) imaging. In vitro experiment results showed that the nanocomposite Pt@Bi2Te3 could effectively increase the uptake of platinum in cancer cells, which could kill tumor cells through the combined effect of PTT and CT. Furthermore, combination therapy of cancer in vivo was achieved with obvious tumor-growth inhibition without inducing observed side effects. We revealed the great potential of Bi2Te3 nanocomposites in increasing therapeutic efficiency by PTT–CT therapy and PA–PT imaging.

研究领域: 肿瘤学 · 生物医学工程 · 材料科学
✓ 已验证 DOI PubMed 高影响因子
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Small · 2019 ·Vol. 16 ·期 1 ·1905208 · IF 10.856

Biodegradable Bi2O2Se Quantum Dots for Photoacoustic Imaging-Guided Cancer Photothermal Therapy

Hanhan Xie,Mingqiang Liu,Baihao You,Guanghong Luo,Yue Chen,Bilu Liu,Zhenyou Jiang,Paul K. Chu,Jundong Shao,Xue-Feng Yu

As new 2D layered nanomaterials, Bi 2 O 2 Se nanoplates have unique semiconducting properties that can benefit biomedical applications. Herein, a facile top-down approach for the synthesis of Bi 2 O 2 Se quantum dots (QDs) in a solution is described. The Bi 2 O 2 Se QDs with a size of 3.8 nm and thickness of 1.9 nm exhibit a high photothermal conversion coefficient of 35.7% and good photothermal stability. In vitro and in vivo assessments demonstrate that the Bi 2 O 2 Se QDs possess excellent photoacoustic (PA) performance and photothermal therapy (PTT) efficiency. After systemic administration, the Bi 2 O 2 Se QDs accumulate passively in tumors enabling efficient PA imaging of the entire tumors to facilitate imaging-guided PTT without obvious toxicity. Furthermore, the Bi 2 O 2 Se QDs which exhibit degradability in aqueous media not only have sufficient stability during in vivo circulation to perform the designed therapeutic functions, but also can be discharged harmlessly from the body afterward. The results reveal the great potential of Bi 2 O 2 Se QDs as a biodegradable multifunctional agent in medical applications.

研究领域: 生物医学工程 · 纳米医学 · 癌症治疗
✓ 已验证 DOI PubMed 高影响因子
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Science of Advanced Materials · 2019 ·Vol. 11 ·期 12 ·1816-1824 · IF 1.158

The Performance of Composite Nanoparticles Based on Fe3O4@SiO2/PLGA/PFOB in Magnetic Resonance Imaging and Photoacoustic Imaging

Qin Huihao,Zhang Wei,Luo Yi,Wei Yubo,Sun Shenglu,Chen Jingya

Polylactic acid glycolic acid (PLGA), a polymer material, is used as a shell and perfluorooctane (PFOB) as the core. Fe3O4@SiO2 nanoparticles are distributed in the shell to prepare a magnetic phase change multifunctional nano emulsion contrast agent (Fe3O4@SiO2/PLGA/PFOB). The ultrasound, magnetic resonance imaging and CT imaging effects of the contrast agent on normal rat liver parenchyma are investigated. Methods: Single emulsification method is used to prepare Fe3O4@SiO2-loaded polymer Fe3O4@SiO2/PLGA/PFOB nanoparticles encapsulated with PLGA. In addition, polymer Fe3O4@SiO2/PLGA nanoparticles loaded with Fe3O4@SiO2 nanoparticles, PLGA@PFOB nanoparticles coated with PLGA and blank PLGA nanoparticles are prepared as experimental control group. Its surface morphology, internal structure, particle size, potential and other general characteristics are tested. RAW264.7 mouse mononuclear macrophages are cultured in vitro. Prussian blue staining is used to observe macrophage phagocytosis after Fe3O4@SiO2/PLGA/PFOB contrast agent is added to incubate for 3 hours. MTT method is used to detect the effect of contrast agent on cell activity. The macrophage suspension engulfed with Fe3O4-PFOB is examined by ultrasound, magnetic resonance and CT. The results showed that Fe3O4@SiO2/PLGA/PFOB is brown emulsion after being dissolved in double distilled water. Under the light microscope and scanning electron microscope, Fe3O4@SiO2/PLGA/PFOB is spherical, with regular shape, uniform size, good dispersity and smooth surface. Macrophages are dependent on the phagocytosis of the contrast medium without affecting the activity of macrophages. Moreover, in vitro imaging experiments, compared with the control group, macrophages phagocytized by Fe3O4@SiO2/PLGA/PFOB have obvious enhancement effects in ultrasound, magnetic resonance and CT imaging. In conclusion, Fe3O4@SiO2/PLGA/PFOB has good stability in vivo, can be engulfed by liver macrophages, and can enhance ultrasound, magnetic resonance and CT imaging of liver parenchyma. It is a safe and effective multifunctional ultrasound contrast agent.

研究领域: 医学影像学 · 材料科学 · 生物医学工程
✓ 已验证 DOI 高影响因子
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ACS Applied Nano Materials · 2024 · IF 5.3

An Ultrasound-Activated Nanozyme Sonosensitizer for Photoacoustic Imaging-Guided Breast Cancer Sonodynamic and Starvation Combination Therapy

Linjie Huang,Yina Su,Xueqi Hu,Yichao Zhang,Guizhen Xu,Simin Chen,Jiaqiong Wu,Siyu Wang,Dongdong Zhang,Zheng Zeng,Shanni Hong,Xiahui Lin

Sonodynamic therapy (SDT) is a promising ultrasound (US)-triggered therapeutic modality for anticancer treatments due to its high penetration, safety, and noninvasiveness. Its therapeutic efficiency is closely related to the performance of sonosensitizers and the oxygen concentration of the tumor microenvironment (TME). Herein, inspired by the adhesion of cocklebur, a rough-surface sonosensitizer gold platinum encapsulated with magnesium silicate loaded with glucose oxidase (AuPt@MgSiO3@GOx, APMS-GOx) with an enzymatic cascade activity was designed to improve delivery capability, produce reactive oxygen species, and reduce the glucose concentration in tumor tissue. The rough surface of APMS-GOx can improve the ability of nanomaterials to deliver to tumor areas. The enzymatic cascade reaction of APMS-GOx can induce starvation therapy and improve the level of oxygen. Adequate oxygen can not only alleviate hypoxia TME but also further convert to singlet oxygen (1O2) by APMS-GOx under US activation. Moreover, the activity of GOx increases due to the involvement of US, resulting in a positive effect on starvation therapy. Furthermore, APMS-GOx exhibits near-infrared absorption properties, providing a photoacoustic imaging-guided combination breast tumor therapy strategy.

研究领域: 肿瘤学 · 生物医学工程 · 影像医学
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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

A dual stimulus-responsive NIR-II photoacoustic probe for precise diagnosis of colon cancer and photothermal-starvation synergistic therapy

Yang Wang,Shulong Wang,Min He,Yanli Luo,Fanggui Ye,Jianniao Tian,Shulin Zhao

Integrating imaging-guided diagnoses with therapeutic strategies holds significant potential in the treatment of cancer and other diseases. Herein, we developed a dual stimulus-responsive nanoagent that is responsive to two specific stimuli, and demonstrated its application to the diagnosis and photothermal-starvation therapy of colon cancer. The elevated levels of H 2 S and glucose in colon cancer cells are used as targets for a dual stimulus-responsive, self-assembled copper-albumin-glucose oxidase@polyaniline (Cu 2 + -BSA-GO x @PANI) nanoplatform. Upon entering colon cancer cells, GO x oxidizes glucose to produce gluconic acid, which leads to the protonation of PANI and the red-shifting of the wavelength of maximum absorbance of the nano-platform from 680 nm to 780 nm. Concurrently, Cu 2+ reacts with H 2 S to form CuS, which further induces a redshift from 780 nm to 830 nm, and significantly enhancing the near-infrared II region absorption intensity and enabling photoacoustic imaging under 1064 nm laser irradiation. Additionally, the consumption of glucose within cancer cells inhibits the generation of ATP, achieving starvation therapy while reducing the expression of tumor heat-shock protein 90 to weaken tumoral thermo-tolerance, resulting in a synergistic anti-tumor effect. In vitro and in vivo analyses indicate that the Cu 2+ -BSA-GOx@PANI nano-platform possesses specific visual diagnostic and therapeutic capabilities for colon cancer, providing a novel strategy for the design of highly effective nanodiagnosis-treatment agents.

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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Theranostics · 2016 · IF 8.854

Versatile pH-response Micelles with High Cell-Penetrating Helical Diblock Copolymers for Photoacoustic Imaging Guided Synergistic Chemo-Photothermal Therapy

Shengyu Shi,Yajing Liu,Yu Chen,Zhihuang Zhang,Yunsheng Ding,Zongquan Wu,Jun Yin,Liming Nie

With high optical absorption efficiency, near infrared (NIR) dyes have been proposed as theranostic agents for fluorescence imaging, photoacoustic imaging (PAI), and photothermal therapy (PTT). However, inherent hydrophobicity and short circulation time of small molecule hinder the further biomedical application. Herein smart amphiphilic copolymer was synthesized containing IR780/camptothecin@poly(ε-caprolactone) (IR780/CPT@PCL) as core, helical poly(phenyl isocyanide) (PPI) blocks as shell with the pH-responsive rhodamine B (RhB) moieties in the core-shell interface. With hydrophilic helical PPI coronas, these micelles present significantly enhanced cell-penetrating capacity that plays a key role in facilitating intracellular delivery of various cargos. By encapsulating CPT and IR780 molecules, the multifunctional self-assemble probe has huge potential to realize functional cooperativity and adaptability for cancer diagnosis and therapy. The in vitro and in vivo experimental results demonstrate that the pH-triggered fluorescent responsiveness and strong acoustic generation permit them efficient fluorescent and PA signal sensing for cancer diagnosis. Moreover, with 808 nm laser irradiation, the generated heat significantly improves the drug release from PCL core, leading to synergetic chemo-photothermal therapy and decreases tumor recurrence rates in mice. Overall, the biocompatible multifunctional micelles with these combined advantages can potentially be utilized for PAI guided disease diagnosis and tumor ablation.

研究领域: 生物材料学 · 医学影像 · 癌症治疗
✓ 已验证 DOI PubMed 高影响因子
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Small · 2025 · IF 12.1

A Hydrogen Sulfide-Activated NIR-II Fluorescence/NIR-I Photoacoustic Dual-Ratiometric Nanoprobe With Unique Recognition Reaction for Precise Visual Diagnosis of Hepatitis Disease

Lixian Huang,Fei Lv,Yidong Bin,Jingjin Zhao,Caiying Li,Shulin Zhao,Shengqiang Hu,Liangliang Zhang

Hydrogen sulfide (H 2 S) is a vital gaseous signaling molecule that plays a central role in various physiological and pathological processes. Given the complementary advantages of fluorescence (FL) and photoacoustic (PA) imaging, there is a growing demand for dual-ratiometric probes that enable precise in vivo monitoring of H 2 S levels. In this study, the use of 2-mercapto-1,3,4-thiadiazole (MTD) as a novel recognition group of H 2 S is presented for the first time, following conjugation with cyanine dyes to obtain a new PA probe Cy-MTD. To achieve dual-ratiometric imaging, Cy-MTD is incorporated into down-conversion nanoparticle (DCNP), resulting in the creation of a pioneering NIR-II FL/NIR-I PA dual-ratiometric nanoprobe DCNP@Cy-MTD. Cy-MTD undergoes the blueshift in absorption from 840 to 670 nm after reaction with H 2 S, enabling NIR-I ratiometric PA imaging of H 2 S by measuring the ratio of PA signal at 670 and 840 nm (PA 670 /PA 840 ). In addition, due to the strong absorption of Cy-MTD ≈840 nm and the overlapping between the absorption spectrum of Cy-MTD and 808 nm excitation band of DCNP, the 808 nm-excited FL emission (F 1550 nm,808Ex ) of DCNP in DCNP@Cy-MTD nanoprobe is quenched through the competitive absorption, while it is restored upon the interaction with H 2 S because of the blueshift in absorption of Cy-MTD. Using the stable FL emission of DCNP under 980 nm excitation (F 1550 nm,980Ex ) as the reference signal, NIR-II ratiometric FL imaging (F 1550 nm,808Ex /F 1550 nm,980Ex ) of H 2 S is achieved. The dual-ratiometric response features of the DCNP@Cy-MTD nanoprobe offer a significant advancement over traditional single-signal or single-modality imaging techniques. By providing enhanced accuracy and reliability, this probe allows for the diagnosis of hepatitis by monitoring the H 2 S, surpassing the capabilities of conventional histopathological methods, which provides a new way for more effective diagnostic strategies for liver diseases.

研究领域: 生物医学工程 · 分子影像学 · 肝脏疾病研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Computational and Structural Biotechnology Journal · 2019 · IF 4.72

Single-Component Bismuth Nanoparticles as a Theranostic Agent for Multimodal Imaging-Guided Glioma Therapy

Shu-Ting Lu,Dan Xu,Ru-Fang Liao,Jia-Zhen Luo,Yu-Hang Liu,Zhen-Hua Qi,Cai-Ju Zhang,Nai-Li Ye,Bo Wu,Hai-Bo Xu

Single-component nanomaterials such as bismuth (Bi) based on nanoparticles (NPs) intrinsically having both diagnostic and therapeutic capabilities are widely needed in biomedical fields. However, their design and fabrication still face enormous challenges. Here, a kind of pure Bi NPs with ultrahigh X-ray attenuation coeffcient was developed and evaluated as a simple but powerful theranostic nanomaterals and potent light-to-heat conversion efficiency for photoacuostic imaging (PAI)/photothermal therapy (PTT) in this study. The prepared pure Bi NPs showed excellent photothermal performance and the temperature of NPs solution (1 mg/mL) increased to 70 °C under near-infrared light irradiation within 4 min. The pure Bi NPs showed obvious enhancement effect both in X-ray computed tomography (CT) and PA imaging modalities in vivo . In addition, the glioma growth was efficiently suppressed by the pure Bi NPs after 808 nm laser irradiation, while maintained the biosafety and low toxicity. Thus, it is notable that this type of Bi nanomaterial has great potential in multi-imaging guided cancer treatment.

研究领域: 生物医学工程 · 纳米医学 · 肿瘤学
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Theranostics · 2015 · IF 8.022

Smart MoS2/Fe3O4 Nanotheranostic for Magnetically Targeted Photothermal Therapy Guided by Magnetic Resonance/Photoacoustic Imaging

Jie Yu,Wenyan Yin,Xiaopeng Zheng,Gan Tian,Xiao Zhang,Tao Bao,Xinghua Dong,Zhongliang Wang,Zhanjun Gu,Xiaoyan Ma,Yuliang Zhao

The ability to selectively destroy cancer cells while sparing normal tissue is highly desirable during the cancer therapy. Here, magnetic targeted photothermal therapy was demonstrated by the integration of MoS 2 (MS) flakes and Fe 3 O 4 (IO) nanoparticles (NPs), where MoS 2 converted near-infrared (NIR) light into heat and Fe 3 O 4 NPs served as target moiety directed by external magnetic field to tumor site. The MoS 2 /Fe 3 O 4 composite (MSIOs) functionalized by biocompatible polyethylene glycol (PEG) were prepared by a simple two-step hydrothermal method. And the as-obtained MSIOs exhibit high stability in bio-fluids and low toxicity in vitro and in vivo . Specifically, the MSIOs can be applied as a dual-modal probe for T 2 -weighted magnetic resonance (MR) and photoacoustic tomography (PAT) imaging due to their superparamagnetic property and strong NIR absorption. Furthermore, we demonstrate an effective result for magnetically targeted photothermal ablation of cancer. All these results show a great potential for localized photothermal ablation of cancer spatially/timely guided by the magnetic field and indicated the promise of the multifunctional MSIOs for applications in cancer theranostics.

研究领域: 生物医学工程 · 纳米医学 · 肿瘤学
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