- 标题
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- 实验方案
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Core–Satellite Nanomedicines for <i>in Vivo</i> Real-Time Monitoring of Enzyme-Activatable Drug Release by Fluorescence and Photoacoustic Dual-Modal Imaging
摘要： It remains an unresolved challenge to achieve spatial and temporal monitoring of drug release from nanomedicines (NMs) in vivo, which is of crucial importance in disease treatment. To tackle this issue, we constructed core?satellite ICG/DOX@Gel-CuS NMs, which consist of gelatin (Gel) nanoparticles (NPs) with payloads of near-infrared fluorochrome indocyanine green (ICG) and chemo-drug doxorubicin (DOX) and surrounding CuS NPs. The fluorescence of ICG was initially shielded by satellite CuS NPs within the intact ICG/DOX@Gel-CuS NMs and increased in proportion to the amount of DOX released from NMs in response to enzyme-activated NMs degradation. For more comprehensive understanding of the drug-release profile, a theoretical model derived from computer simulation was employed to reconstruct the enzyme-activatable drug release of the ICG/DOX@Gel-CuS NMs, which demonstrated the underlying kinetics functional relationship between the released DOX amount and recovered ICG fluorescence intensity. The kinetics of drug release in vivo was assessed by administrating ICG/DOX@Gel-CuS NMs both locally and systemically into MDA-MB-231 tumor-bearing mice. Upon accumulation of ICG/DOX@Gel-CuS NMs in the tumor, overexpressed enzymes triggered the degradation of the gelatin scaffold as well as the release of DOX and ICG, which can be visually depicted with the ICG fluorescence signal increasing only in the tumor area by fluorescence imaging. Additionally, the photoacoustic signal from CuS NPs was independent from the physical status of ICG/DOX@Gel-CuS NMs and hence was utilized for real-time NMs tracking. Thus, by taking advantage of the core?satellite architecture and NMs degradability in tumor site, the DOX release profile of ICG/DOX@Gel-CuS NMs was monitored by fluorescence and photoacoustic dual-modal imaging in a real-time noninvasive manner.
关键词： core?satellite,nanomedicines,drug release in vivo,dual-modal imaging,computer simulation
更新于2025-09-23 15:23:52
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Magnetic targeting core/shell Fe3O4/Au nanoparticles for magnetic resonance/photoacoustic dual-modal imaging
摘要： This study reports magnetic targeting guided magnetic (MR)/photoacoustic (PA) dual-modal imaging by core/shell Fe3O4/Au nanoparticles. In this work, MR imaging provides time-dependent tumor location, and PA imaging reveals high resolution vasculatures inside the tumor. It is noted that the synthesized Fe3O4/Au nanoparticles exhibited higher r2 value up to 329 mM?1 s?1 than previously reported T2 contrast agents. Furthermore, the Fe3O4/Au NPs are applied as a promising candidate for in vivo MR/PA imaging of tumors by intravenously injection into LNCaP tumor-beared mice. The MR/PA imaging results show a significantly enhanced MR/PA images in the tumor site. The prepared core/shell Fe3O4/Au nanoparticles will be widely applicable in multi-modal imaging.
关键词： Fe3O4/Au nanoparticles,Magnetic targeting,PA imaging,Dual-modal imaging,MR imaging
更新于2025-09-23 15:22:29
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Multifunctional Two-Dimensional Core-Shell MXene@Gold Nanocomposites for Enhanced Photo-Radio Combined Therapy in the Second Biological Window
摘要： Multi-functional nanoplatforms with special advantages in the diagnosis and treatment of cancer have been widely explored in nanomedicine. Herein, we synthesize two-dimensional core-shell nanocomposites (Ti3C2@Au) via a seed-growth method starting from the titanium carbide (Ti3C2) nanosheets, a classical type of MXene nanostructure. After growing gold on the surface of Ti3C2 nanosheets, the stability and biocompatibility of the nanocomposites are greatly improved by the thiol modification. And importantly, the optical absorption in the near infrared region (NIR) is enhanced. Utilizing the ability of the high optical absorbance and strong X-ray attenuation, the synthesized Ti3C2@Au nanocomposites are used for photoacoustic (PA) and computed tomography (CT) dual-modal imaging. Importantly, the mild photothermal effect of the Ti3C2@Au nanocomposites could improve the tumor oxygenation, which significantly enhances the radiotherapy (RT). None obvious long-term toxicity of the nanocomposites is found at the injected dose. This work highlights the promise of special properties of MXene-based multifunctional nanostructures for cancer theranostics.
关键词： surface modification,the synergistic effect,combined therapy,titanium carbide nanocomposites,dual-modal imaging
更新于2025-09-23 15:19:57
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Gadolinium-doped carbon quantum dots loaded magnetite nanoparticles as a bimodal nanoprobe for both fluorescence and magnetic resonance imaging
摘要： Nowadays, it is highly desired to develop dual-modal fluorescence and magnetic resonance imaging (FI/MRI) probes in medical imaging because it unites the respective advantages of each imaging modality: high sensitivity of FI and superior spatial resolution of MRI. In this study, a facile strategy to fabricate a new bimodal imaging nanoprobe (Gd-CQDs@N-Fe3O4) was reported by integrating the fluorescence ability of carbon quantum dots (CQDs) and T1 and T2 contrast-enhancing functionality of Gd(Ⅲ) ions and Fe3O4 nanoparticles into a single hybrid nanostructure. The hybrid composites were investigated by FT-IR, XRD, TEM, XPS, VSM, and so on, which confirmed that Gd-CQDs@N-Fe3O4 nanoparticles were successfully obtained and exhibited superparamagnetic property at room temperature. The derived nanoprobes presented an excitation wavelength-independent emission behavior. In addition, r1 and r2 relaxivities of the synthesized imaging nanoprobes were measured to be 5.16 and 115.6 mM-1 s-1, which nominated Gd-CQDs@N-Fe3O4 nanocomposites as a suitable T1-T2 contrast agent. The Gd-CQDs@N-Fe3O4 nanoparticles combining two synergetic imaging modalities showed great potential in FI/MRI dual-modal imaging for a more complementary and accurate detection.
关键词： Gd-doped carbon quantum dots,Fluorescence,Fe3O4,Relaxivity,Dual-modal imaging
更新于2025-09-19 17:13:59
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Dual-Modal Imaging-Guided Precise Tracking of Bioorthogonally Labeled Mesenchymal Stem Cells in Mouse Brain Stroke
摘要： Non-invasive and precise stem cell tracking after transplantation in living subject is very important to monitor both stem cell destinations and their in vivo fate, which was closely related to their therapeutic efficacy. Herein, we developed bicyclo[6.1.0]nonyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-NPs) as a delivery system of dual-modal stem cell imaging probes. Near-infrared fluorescent (NIRF) dye, Cy5.5, was chemically conjugated to the BCN-NPs and then oleic acid-coated superparamagnetic iron oxide nanoparticles (OA-Fe3O4 NPs) were encapsulated into BCN-NPs, in resulting Cy5.5-labeled and OA-Fe3O4 NP-encapsulated BCN-NPs (BCN-dual-NPs). For bioorthogonal labeling of human adipose-derived mesenchymal stem cells (hMSCs), firstly, hMSCs were treated with tetra-acetylated N-azidoacetyl-D-mannosamine (Ac4ManNAz) for generating azide (-N3) groups onto their surface via metabolic glycoengineering. Second, azide groups on the cell surface were successfully chemically labeled with BCN-dual-NPs via bioorthogonal click chemistry in vitro. This bioorthogonal labeling of hMSCs could greatly increase the cell labeling efficiency, safety, and imaging sensitivity, compared to only nanoparticle-derived labeling technology. The dual-modal imaging-guided precise tracking of bioorthogonally labeled hMSCs was tested in the photothrombotic stroke mouse model via intraparenchymal injection. Finally, BCN-dual-NPs-labeled hMSCs could be effectively tracked of their migration from implanted site to brain stroke lesion using NIRF/T2-weighted magnetic resonance (MR) dual-modal imaging for 14 days. Our observation would provide a potential application of bioorthogonally labeled stem cell imaging in regenerative medicine by providing safety and high labeling efficiency in vitro and in vivo.
关键词： metabolic engineering,dual-modal imaging,bioorthogonal click chemistry,stem cell tracking,imaging probe,brain stroke
更新于2025-09-16 10:30:52
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Highly Erbium-Doped Nanoplatform with Enhanced Red Emission for Dual-Modal Optical-Imaging-Guided Photodynamic Therapy
摘要： Generally, luminescence quenching at high doping concentrations typically limits the concentration of doped ions in the lanthanide material to less than 0.05?20 mol %, and this is still a major hindrance in designing nanoplatforms with improved brightness. In this research, a nanoplatform capable of dual-modal imaging and synergetic antitumor cells therapy was designed. NaYF4:x%Er@NaXF4 (x = 5, 25, 50, and 100; X = Lu and Y) core@shell nanoparticles with Er3+ ion concentration up to 100 mol % were synthesized, and the luminescence properties under near-infrared (NIR) excitation were detected. The results show the strong coupled of surface and concentration quenching effects in upconversion nanoparticles (UCNP). Upconversion luminescence (UCL) and NIR-II emission intensity increased with negligible concentration quenching effect under 980 and 800 nm NIR lasers because of the growth of epitaxial shells. Therefore, the enhanced red luminescence transfers energy to photosensitizer ZnPc as the photodynamic therapy (PDT) agent for tumor inhibition efficacy.
关键词： photodynamic therapy,upconversion nanoparticles,luminescence quenching,nanoplatform,synergetic antitumor cells therapy,NaYF4:x%Er@NaXF4,dual-modal imaging
更新于2025-09-10 09:29:36
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Rare earth-functionalized nanodiamonds for dual-modal imaging and drug delivery
摘要： Nanodiamonds (NDs) have attracted much attention in biomedical research for their high chemical stability, low toxicity and good biocompatibility. However, the insufficient fluorescence of NDs largely inhibit their multi-functional bio-applications ， such as simultaneous diagnosis and chemotherapy. Herein, a multifunctional NDs-based nanoparticles(ND-TTA:RE) with excellent fluorescence and paramagnetic properties has been fabricated by covalently functionalizing NDs with rare-earth (RE=Eu3+, Gd3+) 2-Thenoyltrifluoroacetone (TTA) complexes. The NDs-based nanoparticles exhibit intense red emission and could enhance the T1-weighted MR image due to the coordinated RE ions. The in vitro/in vivo experiments demonstrate its large potential for optical and MR imaging. In addition, the ND-TTA:RE also shows good drug storage capability that reach to 375 ug/mg toward anticancer drug doxorubicin (Dox) and exhibits significant pH-dependent drug-release behavior. The MTT assays shows that the as-synthesized ND-TTA:RE have low toxicity in a concentration range from 0 to 150 mg/mL, while the Dox-loaded ND-TTA:RE (ND-TTA:RE-Dox) shows effective chemotherapy towards gastric cancer cells. The dual-mode imaging and drug delivery abilities make ND-TTA:RE a promising nanomaterial for multifunctional applications. In addition, this work may also provide a new strategy for the design of multi-functional nanoplatform.
关键词： Dual-modal imaging,Nanodiamond,Rare earth,Drug delivery.
更新于2025-09-10 09:29:36
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Targeted Methotrexate Prodrug Conjugated With Heptamethine Cyanine Dye Improving Chemotherapy and Monitoring Itself Activating by Dual-Modal Imaging
摘要： Theranostic prodrug plays a vital role in reducing the side effects and evaluating the therapeutic efficiency of prodrug in vivo. In particular, small conjugate-based theranostic prodrugs have attracted much attention because of their clear and simple structures. In this work, we synthesized a novel tumor-targeting and glutathione-activated conjugate-based theranostic prodrug (Cy-SS-MTX). The prodrug was constructed by conjugating Cy (IR780) to methotrexate (MTX) via a disulfide bond. The Cy dye as targeting molecule bring prodrug to cancer cells and then the prodrug was activated by the high levels of glutathione in tumor. In cell experiments, the results showed the excellent ability of prodrug to target tumor. Meanwhile, the prodrug apparently improved the anti-tumor ability and hugely reduced toxicity of free MTX on normal cells. Furthermore, owing to intramolecular charge transfer between Cy and MTX, the Cy structure in the prodrug showed an absorption peak at 654 nm in UV-Vis spectroscopy. However, when the disulfide bond of prodrug was broken by glutathione, a new UV-Vis absorption peak at 802 nm of Cy structure in prodrug was arised. At the same time, the fluorescence (FL) emission peak at 750 nm (excitation at 640 nm) would turn into 808 nm (excitation at 745 nm). What’s more, the photoacoustic (PA) signal with excitation at 680 and 808 nm also changed. The experimental results in vivo showed that the prodrug has been successfully utilized for real-timely tracking MTX activation by FL and PA imaging upon near infrared laser excitation and cancer targeting therapy. Our studies further encourage application of small conjugate-based prodrug based on tumor-targeted heptamethine cyanine dye as reporter group for targeted therapy and real-timely tracking activation of drug.
关键词： small conjugate-based prodrug,heptamethine cyanine dye,dual-modal imaging,targeting therapy,monitoring prodrug activation,theranostic
更新于2025-09-04 15:30:14