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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Nanovesicle-templated nanogel: A dual-modal platform integrating intracellular iron homeostasis disruption for ferroptosis and MRI-guided tumor diagnosis

Jicheng Jiang,Yan Peng,Liyan Qiu

Ferroptosis is an emerging form of cell death resulting from iron-dependent massive accumulation of lipid peroxides (LPOs). Efficient iron delivery and powerful iron homeostasis disruption remain quite challenging. Herein, we designed a nanovesicle-templated nanogel PCG-Fe/DHA facilitated by the self-assembly of amphiphilic polyphosphazene and the in situ coordination of gallic acid-modified chito-oligosaccharide with Fe 3+ to co-deliver iron and dihydroartemisinin (DHA) for ferroptosis cancer therapy. PCG-Fe/DHA exhibited excellent capability of dual drug loading as well as pH-responsive Fe 3+ release and esterase-responsive DHA release. The concurrent delivery of Fe 3+ and DHA synergistically disrupted intracellular iron homeostasis via the supplementation of exogenous Fe 3+ and DHA-induced ferritin degradation, resulting in a surge in the intracellular labile iron pool to initiate the Fenton reaction. Meanwhile, the intracellular redox homeostasis was disrupted due to the decline of glutathione peroxidase 4 (GPX4) abundance by Fe 3+ -depleting glutathione (GSH). As a result, the intracellular ROS and LPOs were distinctly accumulated, which consequently enhanced ferroptosis of tumor cells. After intravenous injection of PCG-Fe/DHA, the tumor inhibition ratio in 4 T1 breast tumor-bearing mice achieved 76.8 %. In addition the nanogel could target tumor and produce 3.1 times higher magnetic resonance imaging (MRI) signal intensity than free Fe. These evidences indicated that PCG-Fe/DHA platform could provide a dual-modal strategy for ferroptosis cancer therapy and MRI-guided tumor diagnosis.

研究领域: 癌症治疗 · 磁共振成像 (MRI) · 纳米技术 · 细胞生物学 · 药学
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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

Nano-Metal–Organic Framework Decorated With Pt Nanoparticles as an Efficient Theranostic Nanoprobe for CT/MRI/PAI Imaging-Guided Radio-Photothermal Synergistic Cancer Therapy

Yingjian Ma,Jing Mao,Haojie Qin,Pan Liang,Wenpeng Huang,Chenchen Liu,Jianbo Gao

The multifunctional theranostic nanoplatforms, which can realize changing the contrasts of medical images and enhance cancer therapies simultaneously, have attracted tremendous attention from chemists and medicine in past decades. Herein, a nanoscale metal–organic framework-based material was first synthesized and then decorated with platinum (NMOF545@Pt) successfully for multimodal imaging-guided synergistic cancer therapy. The obtained NMOF545@Pt is advantageous in shortening the longitudinal relaxation time (T1), enhancing photoacoustic effects, and elevating X-ray absorption efficiently. Thus, the enchantments of tripe imaging modalities, computed tomography (CT)/magnetic resonance imaging (MRI)/photoacoustic imaging (PAI), were realized with NMOF545@Pt administration simultaneously and can be cleared from the mice. Meanwhile, in vitro and in vivo experiments demonstrate that the synthesized NMOF545@Pt can dramatically increase photothermal therapy (PTT) and radiotherapy (RT) efficacy. Convincing evidence proves that tumor growth can be wholly inhibited without noticeable side effects or organ damage. The results demonstrated the promise of multifunctional nanocomposites NMOF545@Pt to improve biomedical imaging and synergistic tumor treatments.

研究领域: 生物医学工程 · 纳米技术 · 癌症研究 · 医学成像
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APL Bioengineering · 2023 ·Vol. 7 ·期 2 · IF 6

Gold nanorods with iron oxide dual-modal bioprobes in SERS-MRI enable accurate programmed cell death ligand-1 expression detection in triple-negative breast cancer

Pan Ting,Zhang Dinghu,Wu Xiaoxia,Li Zihou,Zeng Hui,Xu Xiawei,Zhang Chenguang,He Yiwei,Gong Yuanchuan,Wang Pin,Mao Quanliang,Yao Junlie,Lin Jie,Wu Aiguo,Shao Guoliang

The efficiency of immunotherapy for triple-negative breast cancer (TNBC) is relatively low due to the difficulty in accurately detecting immune checkpoints. The detection of TNBC-related programmed cell death ligand-1 (PD-L1) expression is important to guide immunotherapy and improve treatment efficiency. Surface-enhanced Raman spectroscopy (SERS) and magnetic resonance (MR) imaging exhibit great potential for early TNBC diagnosis. SERS, an optical imaging mode, has the advantages of high detection sensitivity, good spatial resolution, and “fingerprint” spectral characteristics; however, the shallow detection penetration of SERS bioprobes limits its application in vivo . MR has the advantages of allowing deep penetration with no radiation; however, its spatial resolution needs to be improved. SERS and MR have complementary imaging features for tumor marker detection. In this study, gold nanorod and ultrasmall iron oxide nanoparticle composites were developed as dual-modal bioprobes for SERS-MRI to detect PD-L1 expression. Anti-PD-L1 (aPD-L1) was utilized to improve the targeting ability and specificity of PD-L1 expression detection. TNBC cells expressing PD-L1 were accurately detected via the SERS imaging mode in vitro , which can image at the single-cell level. In addition, bioprobe accumulation in PD-L1 expression-related tumor-bearing mice was simply and dynamically monitored and analyzed in vivo using MR and SERS. To the best of our knowledge, this is the first time a SERS-MRI dual-modal bioprobe combined with a PD-L1 antibody has been successfully used to detect PD-L1 expression in TNBC. This work paves the way for the design of high-performance bioprobe-based contrast agents for the clinical immunotherapy of TNBC.

研究领域: 纳米技术 · 癌症生物学 · 医学影像 · 免疫治疗
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Nano Today · 2022 · IF 18.962

A versatile metal–organic nanoplatform in combination with CXCR4 antagonist and PD-L1 inhibitor for multimodal synergistic cancer therapy and MRI-guided tumor imaging

Di Liu,Hongliang He,Fei Kong,Yixiang Cao,Fengchao Zang,Ming Ma,Ning Gu,Yu Zhang

Currently, multimodal synergistic nanoplatform emerges as an important cancer therapy paradigm, however, multimodal synergistic theranostic nanoplatform remains to be developed. Herein, using the mouse model of breast cancer, a versatile multimodal synergistic theranostic nanoplatform is rationally designed and synthesized for enhancing chemodynamic therapy (CDT), overcoming immunosuppression within tumor microenvironment , and inhibiting metastasis as well as tracking tumor. To fulfill our design, a composite Fe/Mn magnetic nanoparticle is first synthesized by loading with Fe 3 O 4 and BMS-202 (PD-L1 inhibitor) within a poly(lactide-co-glycolide)-based nanoparticle core, which are further modified with in situ synthesis of MnO 2 layer. Then, the composite metal-organic nanoparticle is coated with two targeting moieties hyaluronic acid (HA) and AMD3100 (CXCR4 antagonist), respectively, to achieve the multimodal synergistic theranostic nanoplatform ( [email protected] +AMD). With surface targeting modification, [email protected] +AMD exhibits enhanced tumor accumulation, where it effectively consumes endogenous glutathione to generate Mn 2+ allowing for the enhanced CDT effect, alleviates tumor hypoxia by O 2 generation and reverses the tumor immunosuppression. [email protected] +AMD blocks CXCR4 receptor on cancer cells, thus suppressing the CXCR4-mediated cancer metastasis and invasion. Additionally, [email protected] +AMD would synchronously be achieving tumor tracking by T 1 -T 2 dual-mode magnetic resonance imaging. Collectively, this strategy holds a novel multimodal synergistic theranostics for effective cancer management.

研究领域: 纳米技术 · 癌症治疗 · 医学成像 · 免疫疗法 · 药物递送系统
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Science China-Chemistry · 2020 ·Vol. 63 ·期 7 ·924-935 · IF 6.356

Copper-thioguanine metallodrug with self-reinforcing circular catalysis for activatable MRI imaging and amplifying specificity of cancer therapy

Yuan Haifeng,Zhao Yan,Yang Chan,Zhang Cheng,Yang Yue,Meng Hongmin,Huan Shuangyan,Song Guosheng,Zhang Xiaobing

For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic efficacy is also greatly limited by the specificity of tumor microenvironment for reactive oxygen species (ROS) based cancer therapeutic strategy ( e.g. , chemodynamic therapy). Herein, we have developed metal-drug coordination nanoplatform that can not only be responsive to tumor microenvironment but also modulate it, so as to achieve efficient treatment of cancer. Excitingly, by employing small molecule drug (6-thioguanine) as ligand copper ions, we achieve a high drug loading rate (60.1%) and 100% of utilization of metal-drug coordination nanoplatform (Cu-TG). Interestingly, Cu-TG possessed high-efficiently horseradish peroxidase-like, glutathione peroxidase-like and catalase-like activity. Under the tumor microenvironment, Cu-TG exhibited the self-reinforcing circular catalysis that is able to amplify the cellular oxidative stress, inducing notable cancer cellular apoptosis. Moreover, Cu-TG could be activated with glutathione (GSH) and facilitated for GSH triggered 6-TG release, higher selective therapeutic effect toward cancer cells, and GSH activated T 1 weight-magnetic resonance imaging. Based on the above properties, Cu-TG exhibited magnetic resonance imaging (MRI) guiding, efficient and synergistic combination of chemodynamic and chemotherapy with self-reinforcing therapeutic outcomes in vivo .

CAS / MDL: 6156-78-1
研究领域: 癌症治疗 · 药物递送系统 · 纳米技术 · 磁共振成像 · 生物医学工程 · 化学生物学
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LANGMUIR · 2016 · IF 3.993

Improving the MR Imaging Sensitivity of Upconversion Nanoparticles by an Internal and External Incorporation of the Gd3+ Strategy for in Vivo Tumor-Targeted Imaging

Hongli Du,Jiani Yu,Dongcai Guo,Weitao Yang,Jun Wang,Bingbo Zhang

Gd3+-ion-doped upconversion nanoparticles (UCNPs), integrating the advantages of upconversion luminescence and magnetic resonance imaging (MRI) modalities, are capturing increasing attention because they are promising to improve the accuracy of diagnosis. The embedded Gd3+ ions in UCNPs, however, have an indistinct MRI enhancement owing to the inefficient exchange of magnetic fields with the surrounding water protons. In this study, a novel approach is developed to improve the MR imaging sensitivity of Gd3+-ion-doped UCNPs. Bovine serum albumin (BSA) bundled with DTPA-Gd3+ (DTPAGd) is synthesized both as the MR imaging sensitivity synergist and phase-transfer ligand for the surface engineering of UCNPs. The external Gd3+ ion attachment strategy is found to significant improve the MR imaging sensitivity of Gd3+-ion-doped UCNPs. The relaxivity analysis shows that UCNPs@BSA·DTPAGd exhibit higher relaxivity values than do UCNPs@BSA without DTPAGd moieties. Another relaxivity study discloses a striking message that the relaxivity value does not always reflect the realistic MRI enhancement capability. The high concentration of Gd3+-ion-containing UCNPs with further surface-engineered BSA·DTPAGd (denoted as UCNPs–H@BSA·DTPAGd) exhibits a more pronounced MRI enhancement capability compared to the other two counterparts [UCNPs–N@BSA·DTPAGd and UCNPs–L@BSA·DTPAGd (−N and –L are denoted as zero and low concentrations of Gd3+ ion doping, respectively)], even though it holds the lowest r1 of 1.56 s–1 per mmol L–1 of Gd3+. The physicochemical properties of UCNPs are essentially maintained after BSA·DTPAGd surface decoration with good colloidal stability, in addition to improving the MR imaging sensitivity. In vivo T1-weighted MRI shows potent tumor-enhanced MRI with UCNPs–H@BSA·DTPAGd. An in vivo biodistribution study indicates that it is gradually excreted from the body via hepatobiliary and renal processing with no obvious toxicity. It could therefore be concluded, with improved MR imaging sensitivity by an internal and external incorporation of Gd3+ strategy, that UCNPs–H@BSA·DTPAGd presents great potential as an alternative in tumor-targeted MR imaging.

CAS / MDL: 98-10-2 112-88-9
研究领域: 纳米技术 · 医学成像 · 材料科学 · 生物医学工程
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Advanced Healthcare Materials · 2022 ·Vol. 11 ·期 14 ·2200841 · IF 11.092

Self-Confirming Magnetosomes for Tumor-Targeted T1/T2 Dual-Mode MRI and MRI-Guided Photothermal Therapy

Gexuan Jiang,Di Fan,Jiesheng Tian,Zhichu Xiang,Qiaojun Fang

Nanomaterials as T 1 / T 2 dual-mode magnetic resonance imaging (MRI) contrast agents have great potential in improving the accuracy of tumor diagnosis. Applications of such materials, however, are limited by the complicated chemical synthesis process and potential biosafety issues. In this study, the biosynthesis of manganese (Mn)-doped magnetosomes (MagMn) that not only can be used in T 1 / T 2 dual-mode MR imaging with self-confirmation for tumor detection, but also improve the photothermal conversion efficiency for MRI-guided photothermal therapy (PTT) is reported. The MagMn nanoparticles (NPs) are naturally produced through the biomineralization of magnetotactic bacteria by doping Mn into the ferromagnetic iron oxide crystals. In vitro and in vivo studies demonstrated that targeting peptides functionalized MagMn enhanced both T 1 and T 2 MRI signals in tumor tissue and significantly inhibited tumor growth by the further MRI-guided PTT. It is envisioned that the biosynthesized multifunctional MagMn nanoplatform may serve as a potential theranostic agent for cancer diagnosis and treatment.

研究领域: 生物医学工程 · 纳米技术 · 癌症研究 · 分子影像 · 诊疗一体化
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NANOTECHNOLOGY · 2021 ·Vol. 33 ·期 2 ·025101 · IF 3.874

Manganese and dysprosium codoped carbon quantum dots as a potential fluorescent/T1/T2/CT quadri-modal imaging nanoprobe

Chunxing Li,Yun Wang,Huayan Nong,Xiaoxi Hu,Yu Wu,Yanjun Zhang,Caimei Liang,Keguang Chen,Songliang Li

It has been challenging to integrate various medical imaging modalities into an ultra-small nanoparticle with good biocompatibility to build highly efficient multimodal imaging nanoprobes. A new manganese and dysprosium codoped carbon quantum dots (Mn,Dy-CQDs) with a mean diameter of 1.77 nm was synthesized for fluorescence imaging, T1/T2-weighted magnetic resonance imaging (T1/T2-weighted MRI), and x-ray computed tomography (CT) imaging using a simple one-step hydrothermal approach. The obtained Mn,Dy-CQDs showed good water solubility, long-term stability, strong stable fluorescence property (fluorescence quantum yield of 31.62%), and excellent biocompatibility. The cell imaging verified that the Mn,Dy-CQDs have high efficiency of fluorescence imaging. The Mn,Dy-CQDs, on the other hand, had a superior x-ray absorption performance (47.344 HU l g−1), a higher longitudinal relaxivity (r1 = 7.47 mM−1 s−1), a higher transverse relaxivity (r2 = 42.686 mM−1 s−1). In vitro T1/T2-weighted MRI and CT imaging showed that Mn,Dy-CQDs can produce a strong contrast enhancement impact. To summarise, the Mn,Dy-CQDs may be used as a T1/T2-weighted MRI/CT/fluorescent quadri-modal imaging nanoprobe, indicating that they have a lot of uses in biomedical multimode imaging and clinics.

CAS / MDL: 15059-52-6 6381-92-6
研究领域: 材料科学 · 纳米技术 · 生物医学工程 · 医学成像
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2019 ·Vol. 20 ·期 12 ·2988 · IF 4.183

Targeting Pancreatic Cancer Cells with Peptide-Functionalized Polymeric Magnetic Nanoparticles

Xiuliang Zhu,Nan Lu,Ying Zhou,Shaoyan Xuan,Jiaojiao Zhang,Francesca Giampieri,Yongping Zhang,Fangfang Yang,Risheng Yu,Maurizio Battino,Zuhua Wang

Pancreatic cancer is a concealed and highly malignant tumor, and its early diagnosis plays an increasingly weighty role during the course of cancer treatment. In this study, we developed a polymeric magnetic resonance imaging (MRI) nanoplatform for MRI contrast agents. To improve tumor-targeting delivery of MRI contrast agents, we employed a pancreatic cancer targeting CKAAKN peptide to prepare a peptide-functionalized amphiphilic hyaluronic acid–vitamin E succinate polymer (CKAAKN–HA–VES) for delivering ultra-small superparamagnetic iron oxide (USPIO), namely, CKAAKN–HA–VES@USPIO. With the modification of the CKAAKN peptide, CKAAKN–HA–VES@USPIO could specifically internalize into CKAAKN-positive BxPC-3 cells. The CKAAKN–HA–VES@USPIO nanoparticles presented a more specific accumulation into pancreatic cancer cells than normal pancreatic cells, and an obvious decrease in signal intensity was observed in CKAAKN-positive BxPC-3 cells, compared with CKAAKN-negative HPDE6-C7 cells and non-targeting HA–VES@USPIO nanoparticles. The results demonstrated that our polymeric MRI nanoplatform could selectively internalize into CKAAKN-positive pancreatic cancer cells by the specific binding of CKAAKN peptide with pancreatic cancer cell membrane receptors, which provided a novel polymeric MRI contrast agent with high specificity for pancreatic cancer diagnosis, and makes it a very promising candidate for magnetic resonance imaging contrast enhancement.Keywords:pancreatic cancer;CKAAKN peptide;MRI contrast agent;polymer

研究领域: 肿瘤学 · 医学影像学 · 生物材料学
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PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION · 2020 ·Vol. 37 ·期 3 ·1900427 · IF 3.099

Metal–Drug–Protein Assemblies: Gd3+ Self-Enhanced Magnetic Resonance Imaging, High-Sensitive Tumor-Targeting Imaging and Efficient Chemo-Phototherapy

Jia Zhou,Tianliang Li,Yiran Zhang,Xiaoyu Xu,Chunlei Zhang,Yuehua Li,Daxiang Cui,Yingsheng Cheng

Magnetic resonance imaging (MRI) contrast agents are broadly employed for better clinical trials in MR imaging. Magnevist solution (Gd-DTPA), a clinical MRI contrast agent, possesses inherent shortcomings like poor r 1 relaxation, short half-time, nephrotoxicity, etc. To overcome these problems, Gd-DTPA-grafted protein assemblies (Gd-P-ABs) loading with anticancer drug cisplatin and photosentizer IR-780 are constructed via chelation of Gd 3+ . Gd-P-ABs exhibit dual MR/fluorescence (FL) imaging–guided chemo/photothermal therapy. Interestingly, Gd-P-ABs behave as aggregation-enhanced magnetic resonance imaging with an extremely high r 1 value of 26.391 s −1 m m −1 , which is about 5.5-fold larger than Gd-DTPA (≈4.8 s −1 m m −1 ). Consequently, better MRI performance is presented with the same concentration of Gd ions. When exposed to acidic tumor microenvironment and light irradiation, Gd-P-ABs show significant drug release capacity. Good cell killing ability in vitro is also determined due to effective folate-targeting ability and high photo–heat conversion. In vivo MR/FL imaging results reveal that Gd-P-ABs possess high-sensitivity tumor-targeting imaging and long tumor retention, which are attributed to the folate-targeting ability and small size effect. Combined chemo/photothermal therapy in vivo demonstrates that the tumor can be eventually ablated. Altogether, the Gd-P-ABs possess great potential for clinical imaging-guided tumor therapy.

CAS / MDL: 98-10-2 67-68-5 121-44-8
研究领域: 放射学 · 分子影像 · 癌症治疗 · 纳米医学 · 生物医学工程
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ADVANCED FUNCTIONAL MATERIALS · 2017 ·Vol. 27 ·期 11 ·1605313 · IF 12.124

Single Molecular Wells–Dawson-Like Heterometallic Cluster for the In Situ Functionalization of Ordered Mesoporous Carbon: A T 1- and T 2-Weighted Dual-Mode Magnetic Resonance Imaging Agent and Drug Delivery System

Qianqian Zhang,Peiyuan Wang,Yun Ling,Xiaomin Li,Lixue Xia,Yongtai Yang,Xiaofeng Liu,Fan Zhang,Yaming Zhou

Developing a feasible way to prepare highly dispersed heterometallic nanoparticles incorporated in porous carbon composites is of significant importance for multifunctional materials. In this work, heterometallic γ-Fe 2 O 3 and GdPO 4 nanoparticles that are incorporated in ordered mesoporous carbon composites are facilely prepared by a one-pot in situ method using a Wells–Dawson-like cluster of [Fe 6 Gd 6 (μ 3 -O) 2 (CO 3 )(O 3 PPh) 6 (O 2 C t Bu) 18 ] ({Fe 6 Gd 6 P 6 } for short) as the precursor. It is verified that the γ-Fe 2 O 3 and GdPO 4 nanoparticles are highly dispersed and embedded into the carbon matrix with a particle size smaller than 5 nm, even when the carbon matrix is changed from 2D hexagonal P6mm to 3D body-centered cubic Im-3m symmetry. Additionally, a formation mechanism is proposed. Furthermore, dual-mode magnetic resonance (MR) imaging and drug carrier properties are evaluated by in vitro experiments, which show a satisfactory T 1 - and T 2 -weighted MR imaging effect with r 1 and r 2 relaxivity values of 2.7 and 183.7 mM −1 s −1 , respectively, and doxorubicin hydrochloride carrier amount of 102 mg g −1 , identifying a combined function for potential diagnostic and therapy.

研究领域: 材料科学 · 纳米技术 · 生物医学工程 · 磁共振成像 · 药物递送系统
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2016 · IF 3.902

Functionalized magnetic nanochains with enhanced MR imaging: A novel nanosystem for targeting and inhibition of early glioma

Yi Zhang,Zhongbing Huang,Zhi Wu,Guangfu Yin,Lei Wang,Fabao Gao

Absence of efficient targeting limits the application of magnetic nanochains (NCs) in the diagnosis of early brain cancer. Herein, dextran-coated NCs (more than 100   nm length and ∼10   nm cores diameter), which were modified by cyclic pentapeptide c(RGDyC) or chlorotoxin (CTX) as the targeting molecules, were fabricated via carbodiimide chemistry and thiol technique. The analysis results revealed that the obtained slender NCs exhibited good biocompatibility, superparamagnetic property, high transverse relaxivity ( R 2 ) and longer blood circulation time. The test results of human umbilical vein endothelial cells and U251 human glioma cells indicated that the conjugation of c(RGDyC) could obviously increase the cyto-internalization of c(RGDyC)-NCs, however, CTX modification could significantly enhance accumulation of CTX-NCs in U251 cells, leading to cellular apoptosis. The results of in vivo biodistribution tests and in vivo magnetic resonance (MR) imaging indicated that, although the c(RGDyC)-NCs could target early glioma to some extent and obviously enhance the contrast of MR imaging, CTX-NCs possessed higher tumor-targeting ability and good inhibition effect than the c(RGDyC)-NCs, suggesting that CTX-NCs are promising candidates for the diagnosis and therapy of early glioma.

研究领域: 生物医学工程 · 肿瘤学 · 分子影像学
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