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Fluorescence imaging in tumor mice

Felista L Tansi, Ronny Rüger, Ansgar M Kollmeier, Markus Rabenhold, Frank Steiniger, Roland E Kontermann, Ulf K Teichgraeber, Alfred Fahr, Ingrid Hilger
BACKGROUND: Endoglin (CD105) is overexpressed on tumor cells and tumor vasculatures, making it a potential target for diagnostic imaging and therapy of different neoplasms. Therefore, studies on nanocarrier systems designed for endoglin-directed diagnostic and drug delivery purposes would expose the feasibility of targeting endoglin with therapeutics. METHODS: Liposomes carrying high concentrations of a near-infrared fluorescent dye in the aqueous interior were prepared by the lipid film hydration and extrusion procedure, then conjugated to single chain antibody fragments either selective for murine endoglin (termed mEnd-IL) or directed towards human endoglin (termed hEnd-IL)...
March 12, 2018: Biochimica et Biophysica Acta
Xiaoye Yang, Xiaoqun Shi, Jianbo Ji, Guangxi Zhai
The development of imaging-guided smart drug delivery systems for combinational photodynamic/chemotherapy of the tumor has become highly demanded in oncology. Herein, redox-responsive theranostic polymeric nanoparticles (NPs) were fabricated innovatively using low molecular weight heparin (LWMH) as the backbone. Chlorin e6 (Ce6) and alpha-tocopherol succinate (TOS) were conjugated to LMWH via cystamine as the redox-sensitive linker, forming amphiphilic Ce6-LMWH-TOS (CHT) polymer, which could self-assemble into NPs in water and encapsulate paclitaxel (PTX) inside the inner core (PTX/CHT NPs)...
November 2018: Drug Delivery
Changqie Pan, Yuqing Liu, Minyu Zhou, Wensheng Wang, Min Shi, Malcolm Xing, Wangjun Liao
A multifunctional theranostic nanoplatform integrated with environmental responses has been developed rapidly over the past few years as a novel treatment strategy for several solid tumors. We synthesized pH-sensitive poly(β-thiopropionate) nanoparticles with a supermagnetic core and folic acid (FA) conjugation (FA-doxorubicin-iron oxide nanoparticles [FA-DOX@ IONPs]) to deliver an antineoplastic drug, DOX, for the treatment of folate receptor (FR)-overexpressed breast cancer. In addition to an imaging function, the nanoparticles can release their payloads in response to an environment of pH 5, such as the acidic environment found in tumors...
2018: International Journal of Nanomedicine
Yuan-Chung Tsai, Priya Vijayaraghavan, Wen-Hsuan Chiang, Hsin-Hung Chen, Te-I Liu, Ming-Yin Shen, Ayumu Omoto, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu
Therapeutic efficacy of glioblastoma multiforme (GBM) is often severely limited by poor penetration of therapeutics through blood-brain barrier (BBB) into brain tissues and lack of tumor targeting. In this regard, a functionalized upconversion nanoparticle (UCNP)-based delivery system which can target brain tumor and convert deep tissue-penetrating near-infrared (NIR) light into visible light for precise phototherapies on brain tumor was developed in this work. Methods : The UCNP-based phototherapy delivery system was acquired by assembly of oleic acid-coated UCNPs with angiopep-2/cholesterol-conjugated poly(ethylene glycol) and the hydrophobic photosensitizers...
2018: Theranostics
Zhiming Xu, Yangyun Wang, Jianshan Han, Qingqing Xu, Jiawei Ren, Jiaying Xu, Yong Wang, Zhifang Chai
The accurate imaging of the lymph nodes represents a critical indicator for tumor staging and surgical planning (e.g. osteosarcoma). Clinically, nodal tracing using a radionanocolloid is often limited by the inaccessibility of real-time images and inadequate anatomical information. Herein, we present a 99mTc-labeled biomineralization nanoprobe for the advanced detection of osteosarcoma and lymph nodes with multimodal imaging. By exploiting the complementary strengths of MRI/SPECT/NIR fluorescence, the fabricated nanoprobe exhibited suitable stability and biocompatibility characteristics and was shown to be able to locate in osteosarcoma...
March 5, 2018: Analytical Chemistry
Huiqin Zhuo, Baoshi Zheng, Jianming Liu, Yong Huang, Huiling Wang, Duo Zheng, Naiquan Mao, Jinyu Meng, Sufang Zhou, Liping Zhong, Yongxiang Zhao
BACKGROUND: Anti-CD105 mAb-conjugated immunoliposomes, loaded with secreted mouse endostatin gene, were developed for targeted tumor imaging and antiangiogenic gene therapy. METHODS: The liposomes were investigated for size, zeta-potential, lipid content, antibody binding ability, and pcDNA loading capacity. The ability of immunoliposomes to target tumor-derived endothelial cells and perform gene transfer in vitro was measured and their basic biocompatibility was evaluated...
March 2, 2018: Journal of Experimental & Clinical Cancer Research: CR
Tao Liu, Jing Ning, Bo Wang, Bin Dong, Song Li, Xiangge Tian, Zhenlong Yu, Yulin Peng, Chao Wang, Xinyu Zhao, Xiaokui Huo, Cheng-Peng Sun, Jing-Nan Cui, Lei Feng, Xiaochi Ma
Visualization of endogenous disease-associated enzymes is of great clinical significance, as it could allow earlier clinical diagnosis and timely intervention. Herein, we first synthesized and characterized an enzyme-activatable near-infrared fluorescent probe, GP-DM, for determining the activity of dipeptidyl peptidase IV (DPP IV), which is associated with various pathological processes, especially in diabetes and malignant tumors. GP-DM emitted significant turn-on NIR fluorescent signals simultaneously in response to DPP IV, making it favorable for accurately and dynamically monitoring DPP IV activity in vitro and in vivo...
March 1, 2018: Analytical Chemistry
Sharon M Sagnella, Jennifer Trieu, Himanshu Brahmbhatt, Jennifer A MacDiarmid, Alex MacMillan, Renee M Whan, Christopher M Fife, Joshua A McCarroll, Andrew J M Gifford, David S Ziegler, Maria Kavallaris
Advanced stage neuroblastoma is an aggressive disease with limited treatment options for patients with drug resistant tumors. Targeted delivery of chemotherapy for pediatric cancers offers promise to improve treatment efficacy and reduce toxicity associated with systemic chemotherapy. The EnGeneIC delivery vehicle (EDVTM) is a nanocell which can package chemotherapeutic drugs and target tumors via attachment of bispecific proteins to the surface of the nanocell. Phase 1 trials in adults with refractory tumors have shown an acceptable safety profile...
February 28, 2018: Molecular Cancer Therapeutics
Xiaoxia Cui, Qi Fan, Shengjia Shi, Weihong Wen, Duofang Chen, Haitao Guo, Yantao Xu, Fei Gao, Rongzhi Nie, Harold D Ford, Gordon H Tang, Chaoqi Hou, Bo Peng
Fluorescence imaging signal is severely limited by the quantum efficiency and emission wavelength. To overcome these challenges, novel NIR-emitting K5NdLi2F10 nanoparticles under NIR excitation was introduced as fluorescence imaging probe for the first time. The photostability of K5NdLi2F10 nanoparticles in the water, PBS, FBS and living mice was investigated, respectively. The fluorescence signal was detected with depths of 3.5 and 2.0 cm in phantom and pork tissue, respectively. Fluorescence spectrum with a significant signal-to-background ratio of 10:1 was captured achieved in living mice...
February 28, 2018: Nanotechnology
Jiaying Lin, Weiwei Hu, Fengli Gao, Jinbao Qin, Chen Peng, Xinwu Lu
It has been a great challenge to develop multifunctional fluorescent nanoprobes for tumor-targeted imaging. In this study, we developed folic acid (FA) gold nanoparticles (AuNPs) through diatrozic acid (DTA) linking for in vitro and in vivo targeted imaging of HeLa cervical cancer cells by computed tomography (CT). G5 dendrimers were used as templates to synthesize AuNPs within the interiors of dendrimers. The synthesized AuNPs were then sequentially modified by fluorescein isothiocyanate, FA, and DTA and the remaining terminal amines on the dendrimers were acetylated...
2018: Journal of Cancer
Meng Li, Yisheng Xu, Jinli Sun, Mingwei Wang, Dahai Yang, Xuhong Guo, Haiyun Song, Song Cao, Yunfeng Yan
Traditional charge-conversion nanoparticles (NPs) need the breakage of acid-labile groups on the surface which impedes the rapid response to the acidic microenvironment. Here, we developed novel rod-like charge-conversion NPs with amphiphilic Dex-b-PLGA, PDMAEMA-b-PCL, and an AIE-active probe through Flash Nanoprecipitation (FNP). These NPs exhibit reversible negative-to-positive charge transition at slightly acidic pH relying on the rapid protonation/deprotonation of polymers. The size and the critical charge-conversion pH can be further tuned by varying the flow rate and polymer ratio...
February 22, 2018: ACS Applied Materials & Interfaces
Wendy Bernhard, Ayman El-Sayed, Kris Barreto, Carolina Gonzalez, Wayne Hill, Angel Casaco Parada, Humphrey Fonge, C Ronald Geyer
Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody that is approved in many countries for the treatment of EGFR-positive cancers. Near infrared (NIR) fluorescent dye-labeled antibodies represent an attractive class of image-guided surgical probes because of their high specificity, tumor uptake, and low dissociation from tumor cells that express the antigen. In this study, we developed a NIR fluorescent dye-labeled nimotuzumab immunoconjugate, IRDye800CW-nimotuzumab, and evaluated in vitro binding with EGFR-positive cells, in vivo tumor uptake by NIR fluorescent imaging, and ex vivo biodistribution...
January 19, 2018: Oncotarget
Tingsheng Lin, Xiaozhi Zhao, Sheng Zhao, Hang Yu, Wenmin Cao, Wei Chen, Hui Wei, Hongqian Guo
Photodynamic therapy (PDT) is an emerging effective treatment for cancer. However, the great promise of PDT for bladder cancer therapy has not yet been realized because of tumor hypoxia. To address this challenge, we fabricated O2 -generating HSA-MnO2 -Ce6 NPs (HSA for human serum albumin, Ce6 for chlorin e6, and NPs for nanoparticles) to overcome tumor hypoxia and thus enhance the photodynamic effect for bladder cancer therapy. Methods: The HSA-MnO2 -Ce6 NPs were prepared. We investigated the O2 generation of NPs in vitro and in vivo ...
2018: Theranostics
Andrew M Prantner, Catherine Yin, Kalika Kamat, Khushboo Sharma, Andrew C Lowenthal, Peter Bawden Madrid, Nathalie Scholler
Mesothelin is an epithelial marker highly expressed at the cell surface of cancer cells from diverse origins, including ovarian and pancreatic adenocarcinomas and mesotheliomas. Previously, we identified and characterized an anti-mesothelin nanobody (NbG3a) for in vitro diagnostic applications. The main goal of this research was to establish the potential of NbG3a as a molecular imaging agent. Site-specific biotinylated NbG3a (bNbG3a) was bound to streptavidin-conjugated reagents for in vitro and in vivo assays...
February 20, 2018: Molecular Pharmaceutics
Yuanyuan Zhang, Dan Yang, Hongzhong Chen, Wei Qi Lim, Fiona Soo Zeng Phua, Guanghui An, Piaoping Yang, Yanli Zhao
In this study, a reduction-sensitive supramolecular polymeric drug delivery system was developed for combinational photothermal-chemotherapy of cancer. The multifunctional system was self-assembled by specific host-guest interactions between hydrophilic β-cyclodextrin functionalized hyaluronic acid and adamantane linked camptothecin/dye conjugate, where a near-infrared (NIR) absorbing dye IR825 was loaded. The hydrophilic hyaluronic acid shell endows the assembly with excellent colloidal stability and biocompatibility...
February 9, 2018: Biomaterials
Reju George Thomas, Myeong Ju Moon, Suchithra Poilil Surendran, Hyeong Ju Park, In-Kyu Park, Byeong-Il Lee, Yong Yeon Jeong
PURPOSE: Paclitaxel (PTX) loaded hydrophobically modified glycol chitosan (HGC) micelle is biocompatible in nature, but it requires cancer targeting ability and stimuli release property for better efficiency. To improve tumor retention and drug release characteristic of HGC-PTX nanomicelles, we conjugated cancer targeting heptamethine dye, MHI-148, which acts as an optical imaging agent, targeting moiety and also trigger on-demand drug release on application of NIR 808 nm laser. PROCEDURES: The amine group of glycol chitosan modified with hydrophobic 5β-cholanic acid and the carboxyl group of MHI-148 were bonded by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide chemistry...
February 15, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Tessa Buckle, Danny M van Willigen, Silvia J Spa, Albertus W Hensbergen, Steffen van der Wal, Clarize M de Korne, Mick M Welling, Henk G van der Poel, James C H Hardwick, Fijs W B van Leeuwen
Objectives: The potential of (receptor-mediated) fluorescence-based image-guided surgery tracers is generally linked to the near-infrared emission profile and good manufacturing production (GMP) availability of fluorescent dyes. Surprisingly, little is known about the critical interaction between the structural composition of the dye and the pharmacokinetics of the tracers. In this study, a bimodal/hybrid tracer design was used to systematically and quantitatively evaluate the influence of elongation of the polymethine chain in a fluorescent cyanine (Cy) dye on the imaging potential of a targeted (RGD-based) tracer...
February 15, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Ann L B Seynhaeve, Timo L M Ten Hagen
Tumor and tumor vessel development, as well as tumor response to therapeutics, are highly dynamic biological processes. Histology provides static information and is often not sufficient for a correct interpretation. Intravital evaluation, in which a process is followed in time, provides extra and often unexpected information. With the creation of transgenic animals expressing cell-specific markers and live cell tracers, improvements to imaging equipment, and the development of several imaging chambers, intravital microscopy has become an important tool to better understand biological processes...
January 19, 2018: Journal of Visualized Experiments: JoVE
Yang Qiao, Joy Gumin, Christopher J MacLellan, Feng Gao, Richard Bouchard, Frederick F Lang, R Jason Stafford, Marites P Melancon
OBJECTIVE: To evaluate the feasibility of visualizing bone marrow-derived human mesenchymal stem cells (MSCs) labeled with a gold-coated magnetic resonance (MR)-active multifunctional nanoparticle and injected via the carotid artery for assessing the extent of MSC homing in glioma-bearing mice. MATERIALS AND METHODS: Nanoparticles containing superparamagnetic iron oxide coated with gold (SPIO@Au) with a diameter of ∼82 nm and maximum absorbance in the near infrared region were synthesized...
April 20, 2018: Nanotechnology
Sajal K Ghosh, Abhishek Ganta, Remco A Spanjaard
BACKGROUND: Chemotherapy and targeted therapies have made important strides in cancer treatment yet they often fail and new therapies are still needed. Here, we employed a phenotypic screen to identify and analyze the mechanism of action of novel small molecules that interfere with critical pathways involved in tumor cell growth, using chemoresistant A375 melanoma cells as a model. METHODS: Cell culture studies were performed in ATCC-recommended media. Compounds, and compound libraries were obtained from Boston University or purchased commercially...
February 8, 2018: Journal of Biomedical Science
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