共查询到20条相似文献,搜索用时 15 毫秒
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Ultrasmall Nanoplatforms as Calcium‐Responsive Contrast Agents for Magnetic Resonance Imaging 下载免费PDF全文
Albert Moussaron Sandip Vibhute Andrea Bianchi Serhat Gündüz Shady Kotb Lucie Sancey Vincent Motto‐Ros Silvia Rizzitelli Yannick Crémillieux Francois Lux Nikos K. Logothetis Olivier Tillement Goran Angelovski 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(37):4900-4909
The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle‐based, calcium‐responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA‐USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA‐USRPs on a multigram scale. The resulting platforms display the desired MRI activity—i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca2+. Cell viability is probed with the MTT assay using HEK‐293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA‐USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl2 is also administrated. Laser‐induced breakdown spectroscopy experiments confirm accumulation of SCA‐USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium‐sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium‐dependent physiological and pathological processes in a dynamic manner. 相似文献
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A Tumor‐Specific Cascade Amplification Drug Release Nanoparticle for Overcoming Multidrug Resistance in Cancers 下载免费PDF全文
Mingzhou Ye Yuxin Han Jianbin Tang Ying Piao Xiangrui Liu Zhuxian Zhou Jianqing Gao Jianghong Rao Youqing Shen 《Advanced materials (Deerfield Beach, Fla.)》2017,29(38)
A cascade amplification release nanoparticle (CARN) is constructed by the coencapsulation of β‐lapachone and a reactive‐oxygen‐species (ROS)‐responsive doxorubicin (DOX) prodrug, BDOX, in polymeric nanoparticles. Releasing β‐lapachone first from the CARNs selectively increases the ROS level in cancer cells via NAD(P)H:quinone oxidoreductase‐1 (NQO1) catalysis, which induces the cascade amplification release of DOX and overcomes multidrug resistance (MDR) in cancer cells, producing a remarkably improved therapeutic efficacy against MDR tumors with minimal side effects. 相似文献
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Lei Rong Hui‐Zhen Jia Si Chen Xiang‐Ji Liu Guo‐Feng Luo Ren‐Xi Zhuo Xian‐Zheng Zhang 《Small (Weinheim an der Bergstrasse, Germany)》2014,10(3):599-608
Graphene oxide (GO)‐based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti‐tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)‐co‐poly(ethylene glycol) (PEI‐PEG) grafted GO via a MMP2‐cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over‐expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI‐bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology‐responsive therapeutic function. 相似文献
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Microfluidic Synthesis of pH‐Sensitive Multicompartmental Microparticles for Multimodulated Drug Release 下载免费PDF全文
Hyeon Ung Kim Dae Gun Choi Yoon Ho Roh Min Suk Shim Ki Wan Bong 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(25):3463-3470
Stimuli‐responsive carriers releasing multiple drugs have been researched for synergistic combinatorial cancer treatment with reduced side‐effects. However, previously used drug carriers have limitations in encapsulating multiple drug components in a single carrier and releasing each drug independently. In this work, pH‐sensitive, multimodulated, anisotropic drug carrier particles are synthesized using an acid‐cleavable polymer and stop‐flow lithography. The particles exhibit a faster drug release rate at the acidic pH of tumors than at physiological pH, demonstrating their potential for tumor‐selective drug release. The drug release rate of the particles can be adjusted by controlling the monomer composition. To accomplish multimodulated drug release, multicompartmental particles are synthesized. The drug release profile of each compartment is programmed by tailoring the monomer composition. These pH‐sensitive, multicompartmental particles are promising drug carriers enabling tumor‐selective and multimodulated release of multiple drugs for synergistic combination cancer therapy. 相似文献
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Yongfei Li Mie Chen Bowen Yao Xun Lu Boyang Song Shauna N. Vasilatos Xiang Zhang Xiaomei Ren Chang Yao Weihe Bian Lizhu Sun 《Small (Weinheim an der Bergstrasse, Germany)》2020,16(32)
Poor deep tumor penetration and incomplete intracellular drug release remain challenges for antitumor nanomedicine application in clinical settings. Herein, a nanomedicine (RLPA‐NPs) is developed that can achieve prolonged blood circulation, deep tumor penetration, active‐targeting of cancer cells, endosome/lysosome escape, and intracellular selectivity self‐amplified drug release for effective drug delivery. The RLPA‐NPs are constructed by encapsulation of a pH‐sensitive polymer octadecylamine‐poly(aspartate‐1‐(3‐aminopropyl) imidazole) (OA‐P(Asp‐API)) and a ROS‐generation agent, β‐Lapachone (Lap), in micelles assembled by the tumor‐penetration peptide internalizing RGD (iRGD)‐modified ROS‐responsive paclitaxel (PTX)‐prodrug. iRGD could promote RLPA‐NPs penetration into deep tumor tissue, and specific targeting to cancer cells. After internalization by cancer cells through receptor‐mediated endocytosis, OA‐P(Asp‐API) can rapidly protonate in the endosome's acidic environment, resulting in RLPA‐NPs escape from the endosome through the “proton sponge effect”. At the same time, the RLPA‐NPs micelle disassembles, releasing Lap and PTX‐prodrug. Subsequently, the released Lap could generate ROS, consequently amplifying and accelerating PTX release to kill tumor cells. The in vitro and in vivo studies demonstrated that RLPA‐NPs can significantly improve the therapeutic effect compared to control groups. Therefore, RLPA‐NPs are a promising nanoplatform for overcoming multiple physiological and pathological barriers to enhance drug delivery. 相似文献
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Deep Tumor Penetrating Bioparticulates Inspired Burst Intracellular Drug Release for Precision Chemo‐Phototherapy 下载免费PDF全文
Ruoning Wang Yue Han Bo Sun Ziqiang Zhao Yaw Opoku‐Damoah Hao Cheng Huaqing Zhang Jianping Zhou Yang Ding 《Small (Weinheim an der Bergstrasse, Germany)》2018,14(12)
The relevance of personalized medicine has inspired research for individually concerted diagnosis and therapy. Numerous efforts are devoted to designing drug particulates with capabilities of tumor penetrating and subcellular trafficking to concurrently discharge theranostics in response to multistimulations. In this study, a bioinspired particulate, formulated with whole components of native high‐density lipoproteins (HDLs) and decorated with the tumor‐penetrating peptide iRGD, is proposed to promote tumor penetration of HDLs (pHDLs) together with payloads. Specifically, paclitaxel (PTX), and the NIR fluorescent probe indocyanine green (ICG) are integrated into pHDLs (pHDL/PTX‐ICG) for synergetic chemo‐phototherapy. Inspired by lipoproteins, pHDLs are not only restored from naturally occurring materials but also possessed artificially endowed functions, leading to an enhanced cellular uptake, higher accumulation, and deep penetration into tumors without causing appreciable adverse effects, compared to reconstituted HDLs or lipid‐based nanoparticles. After intravenous administration, pHDL/PTX‐ICG performs a burst of intracellular drug release and imaging‐guided precision chemo‐phototherapy upon NIR irradiation that completely eradicates xenograft tumors. Neither recurrence nor significant toxicity is observed due to maneuvered regional photodynamic and photothermal therapy. Taken together, pHDL/PTX‐ICG is proven to be a promising platform to achieve deep tumor penetration and imaging‐guided chemo‐phototherapy. 相似文献
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Mengxing Wei Lulu Wang Yanfang Wang Tong Zhang Chenchen Wang Chengfan Wu Changlin Tian Gaolin Liang Yue Yuan 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(29):2300015
Magnetic resonance imaging (MRI) is a superior and noninvasive imaging technique with unlimited tissue penetration depth and superb spatiotemporal resolution, however, using intracellular self-assembly of Gd-containing nanoparticles to enhance the T2-weighted MR contrast of cancer cells in vivo for precise tumor MRI is rarely reported. The lysosomal cysteine protease cathepsin B (CTSB) is regarded as an attractive biomarker for the early diagnosis of cancers and metastasis. Herein, taking advantage of a biocompatible condensation reaction, a “smart” Gd-based CTSB-responsive small molecular contrast agent VC-Gd-CBT is developed, which can self-assemble into large intracellular Gd-containing nanoparticles by glutathione reduction and CTSB cleavage to enhance the T2-weighted MR contrast of CTSB-overexpressing MDA-MB-231 cells at 9.4 T. In vivo T2-weighted MRI studies using MDA-MB-231 murine xenografts show that the T2-weighted MR contrast change of tumors in VC-Gd-CBT-injected mice is distinctly larger than the mice injected with the commercial agent gadopentetate dimeglumine, or co-injected with CTSB inhibitor and VC-Gd-CBT, indicating that the accumulation of self-assembled Gd-containing nanoparticles at tumor sites effectively enhances the T2-weighted MR tumor imaging. Hence, this CTSB-targeted small molecule VC-Gd-CBT has the potential to be employed as a T2 contrast agent for the clinical diagnosis of cancers at an early stage. 相似文献
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Zheyu Shen Wenpei Fan Zhen Yang Yijing Liu Vladimir I. Bregadze Swadhin K. Mandal Bryant C. Yung Lisen Lin Ting Liu Wei Tang Lingling Shan Yuan Liu Shoujun Zhu Sheng Wang Weijing Yang L. Henry Bryant Duong T. Nguyen Aiguo Wu Xiaoyuan Chen 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(41)
Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non‐specificity, and low r1) that limit their applications. Herein, a wet‐chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES‐GON‐PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T1‐weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r1 = 70.2 ± 1.8 mM?1 s?1, and r2/r1 = 1.02 ± 0.03, at 1.5 T). The r1 is much higher and the r2/r1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES‐GON‐PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES‐GON‐PAA@RGD2) for T1‐weighted MRI of tumors that overexpress RGD receptors (i.e., integrin αvβ3). The maximum signal enhancement (ΔSNR) for T1‐weighted MRI of tumors reaches up to 372 ± 56% at 2 h post‐injection of ES‐GON‐PAA@RGD2, which is much higher than commercial Gd‐chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES‐GON‐PAA@RGD2 with remarkable relaxivities is a promising and powerful T1‐weighted MRI contrast agent. 相似文献
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Zhenni Wei Zhenqi Jiang Chunshu Pan Jianbi Xia Kaiwei Xu Ting Xue Bo Yuan Ozioma Udochukwu Akakuru Chengjie Zhu Guilong Zhang Zheng Mao Xiaozhong Qiu Aiguo Wu Zheyu Shen 《Small (Weinheim an der Bergstrasse, Germany)》2020,16(11)
The market of available contrast agents for clinical magnetic resonance imaging (MRI) has been dominated by gadolinium (Gd) chelates based T1 contrast agents for decades. However, there are growing concerns about their safety because they are retained in the body and are nephrotoxic, which necessitated a warning by the U.S. Food and Drug Administration against the use of such contrast agents. To ameliorate these problems, it is necessary to improve the MRI efficiency of such contrast agents to allow the administration of much reduced dosages. In this study, a ten‐gram‐scale facile method is developed to synthesize organogadolinium complex nanoparticles (i.e., reductive bovine serum albumin stabilized Gd‐salicylate nanoparticles, GdSalNPs‐rBSA) with high r1 value of 19.51 mm ?1 s?1 and very low r2/r1 ratio of 1.21 (B0 = 1.5 T) for high‐contrast T1‐weighted MRI of tumors. The GdSalNPs‐rBSA nanoparticles possess more advantages including low synthesis cost (≈0.54 USD per g), long in vivo circulation time (t1/2 = 6.13 h), almost no Gd3+ release, and excellent biosafety. Moreover, the GdSalNPs‐rBSA nanoparticles demonstrate excellent in vivo MRI contrast enhancement (signal‐to‐noise ratio (ΔSNR) ≈ 220%) for tumor diagnosis. 相似文献
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Smart‐Dust‐Nanorice for Enhancement of Endogenous Raman Signal,Contrast in Photoacoustic Imaging,and T2‐Shortening in Magnetic Resonance Imaging 下载免费PDF全文
Christoph Pohling Jos L. Campbell Timothy A. Larson Dominique Van de Sompel Jelena Levi Sanjiv S. Gambhir 《Small (Weinheim an der Bergstrasse, Germany)》2018,14(19)
Raman microspectroscopy provides chemo‐selective image contrast, sub‐micrometer resolution, and multiplexing capabilities. However, it suffers from weak signals resulting in image‐acquisition times of up to several hours. Surface‐enhanced Raman scattering (SERS) can dramatically enhance signals of molecules in close vicinity of metallic surfaces and overcome this limitation. Multimodal, SERS‐active nanoparticles are usually labeled with Raman marker molecules, limiting SERS to the coating material. In order to realize multimodal imaging while acquiring the rich endogenous vibronic information of the specimen, a core–shell particle based on “Nanorice”, where a spindle‐shaped iron oxide core is encapsulated by a closed gold shell, is developed. An ultrathin layer of silica prevents agglomeration and unwanted chemical interaction with the specimen. This approach provides Raman signal enhancement due to plasmon resonance effects of the shell while the optical absorption in the near‐infrared spectral region provides contrast in photoacoustic tomography. Finally, T2‐relaxation of a magnetic resonance imaging (MRI) experiment is altered by taking advantage of the iron oxide core. The feasibility for Raman imaging is evaluated by nearfield simulations and experimental studies on the primate cell line COS1. MRI and photoacoustics are demonstrated in agarose phantoms illustrating the promising translational nature of this strategy for clinical applications in radiology. 相似文献
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Lucia Cardo Lydia Martínez-Parra Michele Cesco Begoña M. Echeverría-Beistegui Marta Martínez-Moro Natalia Herrero-Álvarez Marta-Beraza Cabrerizo Susana Carregal-Romero Pedro Ramos-Cabrer Jesús Ruiz-Cabello Maurizio Prato 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(31):2206442
Carbon Dots (CDs) are luminescent quasi-spherical nanoparticles, possessing water solubility, high biocompatibility, and tunable chemical and physical properties for a wide range of applications, including nanomedicine and theranostics. The evaluation of new purification criteria, useful to achieve more reliable CDs, free from the interference of artifacts, is currently an object of debate in the field. Here, new CDs doped with gadolinium (Gd (III)), named Gd@CNDs, are presented as multifunctional probes for Magnetic Resonance Imaging (MRI). This new system is a case of study, to evaluate and/or combine different purification strategies, as a crucial approach to generate CDs with a better performance. Indeed, these new amorphous Gd@CNDs display good homogeneity, and they are free from emissive side products. Gd@CNDs (7–10 nm) contain 7% of Gd (III) w/w, display suitable and stable longitudinal relaxivity (r1) and with emissive behavior, therefore potentially useful for both MR and fluorescence imaging. They show good biocompatibility in both cellular and in vivo studies, cell permeability, and the ability to generate contrast in cellular pellets. Finally, MRI recording T1-weighted images on mice after intravenous injection of Gd@CNDs, show signal enhancement in the liver, spleen, and kidney 30 min postinjection. 相似文献
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Qichen Zhan Xianqing Shi Jiahong Zhou Lin Zhou Shaohua Wei 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(3)
Controlled drug release systems can enhance the safety and availability but avoid the side effect of drugs. Herein, the concept of DNA complementary base pairing rules in biology is used to design and prepare a photothermal‐triggered drug release system. Adenine (A) modified polydopamine nanoparticles (A‐PDA, photothermal reagent) can effectively bind with thymine (T) modified Zinc phthalocyanine (T‐ZnPc, photosensitizer) forming A‐PDA = T‐ZnPc (PATP) complex based on A = T complementary base pairing rules. Similar to DNA, whose base pairing in double strands will break by heating, T‐ZnPc can be effectively released from A‐PDA after near infrared irradiation–triggered light‐thermal conversion to obtain satisfactory photodynamic–photothermal synergistic tumor treatment. In addition, PDA can carry abundant Gd3+ to provide magnetic resonance imaging guided delivery and theranostic function. 相似文献