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Hao Wu, Haohan Wu, Yanni He, Zhen Gan, Zhili Xu, Meijun Zhou, Sai Liu, Hongmei Liu
Background: Rheumatoid arthritis (RA) is a common inflammatory disorder characterized primarily by synovitis and pannus formation in multiple joints, causing joints destruction and irreversible disability in most cases. Early diagnosis and effective therapy monitoring of RA are of importance for achieving the favorable prognosis. Methods: We first prepared the targeted fluorescence probes, and then explored the feasibility of near-infrared (NIR) fluorescence molecular imaging to detect and evaluate the RA via the targeted fluorescence probes by quantitative analysis in this study...
2018: International Journal of Nanomedicine
Anqing Zhu, Huizi Sha, Shu Su, Fangjun Chen, Jia Wei, Fanyan Meng, Yang Yang, Juan Du, Jie Shao, Fuzhi Ji, Chong Zhou, Zhengyun Zou, Xiaoping Qian, Baorui Liu
Efficient trafficking of lymphocytes to the tumor microenvironment is crucial for the success of an effective antitumor immunotherapy. A major challenge to achieve effective adoptive immunotherapy is poor tumor penetration and inefficient migration of T cells to the tumor site. Several approaches to facilitate the trafficking of lymphocytes to the tumor microenvironment have been suggested to overcome these obstacles. Here, we address this issue with a focus on the tumor-penetrating peptide iRGD, which can specifically increase the permeability of the tumor vasculature and tumor tissue, enhancing drug penetration...
2018: American Journal of Cancer Research
Cuihua Hu, Xiaolong Chen, Yibing Huang, Yuxin Chen
To improve the specificity and penetration of anticancer peptides against tumors, in this study, we examined the effects of co-administration of the membrane-active peptide HPRP-A1 and the tumor homing/penetrating peptide iRGD. iRGD peptide is widely recognized as an efficient cell membrane penetration peptide targeting to αvβ3 integrins and neuropilin-1 (NRP-1) receptors, which show high expression in many tumor cells. The anticancer activity, cancer specificity and penetration activity in vitro and in vivo of the co-administered peptides were examined on 2D monolayer cells, 3D multi-cellular spheroids (MCS) and xenograft nude mice...
February 2, 2018: Scientific Reports
Ruoning Wang, Yue Han, Bo Sun, Ziqiang Zhao, Yaw Opoku-Damoah, Hao Cheng, Huaqing Zhang, Jianping Zhou, Yang Ding
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...
March 2018: Small
Fataneh Karandish, James Froberg, Pawel Borowicz, John C Wilkinson, Yongki Choi, Sanku Mallik
Often cancer relapses after an initial response to chemotherapy because of the tumor's heterogeneity and the presence of progenitor stem cells, which can renew. To overcome drug resistance, metastasis, and relapse in cancer, a promising approach is the inhibition of cancer stemness. In this study, the expression of the neuropilin-1 receptor in both pancreatic and prostate cancer stem cells was identified and targeted with a stimuli-responsive, polymeric nanocarrier to deliver a stemness inhibitor (napabucasin) to cancer stem cells...
March 1, 2018: Colloids and Surfaces. B, Biointerfaces
Takahito Kawano, Masaharu Murata, Jeong-Hun Kang, Jing Shu Piao, Sayoko Narahara, Fuminori Hyodo, Nobuhito Hamano, Jie Guo, Susumu Oguri, Kenoki Ohuchida, Makoto Hashizume
Contrast agents with greater specificity and sensitivity are required for the diagnosis of pancreatic cancers by magnetic resonance imaging (MRI). In this study, small heat shock protein 16.5 (Hsp16.5)-based nanocages conjugated to gadolinium(III)-chelated contrast agents and iRGD peptides (which target neuropilin-1 expressed on pancreatic cancer cells) were developed. To investigate whether template size influences relaxivity, nanocages with one to four hydrophobic domains were designed. MRI data showed that larger nanocages had higher T1 relaxivity than smaller nanocages, which resulted from a reduction in molecular tumbling rates caused by an increase in nanocage size, and a robust cage structure resulting from the introduction of hydrophobic domains...
October 20, 2017: Biomaterials
Zhen Gan, Hao Wu, Hao-Han Wu, Mei-Jun Zhou, Fei Yan, Hong-Mei Liu
OBJECTIVE: To prepare internalized RGD (iRGD) modified echogenic liposomes containing methotrexate (MTX) and indocyanine green (ICG) (iRGD MTX ICG ELIP) and evaluate its targeting efficiency and inhibitory effect combined with ultrasound on synovial cells. METHODS: iRGD MTX ICG ELIP was prepared by the thin film rehydration and freeze-lyophilization method and its general characteristics and acoustic responsiveness were assessed. The targeting effect of the prepared liposome was observed by assessing its cell uptake in vitro...
October 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Yin Ren, Jessica E Sagers, Lukas D Landegger, Sangeeta N Bhatia, Konstantina M Stankovic
Vestibular schwannoma (VS) is the most common tumor of the cerebellopontine angle, and it typically presents with sensorineural hearing loss. The genomic landscape of schwannoma is complex and many of the molecules implicated in VS pathogenesis represent targets not amenable to antibody-based or small molecule therapeutics. Tumor-targeted delivery of small interfering RNA (siRNA) therapeutics provides a direct and effective means to interrogate targets while minimizing off-target effects. To establish a preclinical model for therapeutic inhibition of putative targets in VS, archived tumor specimens, fresh tumor cells derived from patients with sporadic VS, and an established schwannoma cell line were screened...
October 10, 2017: Scientific Reports
Dan Yang, Huasen Wang, Chengjie Sun, Hui Zhao, Kuan Hu, Weirong Qin, Rui Ma, Feng Yin, Xuan Qin, Qianling Zhang, Yongye Liang, Zigang Li
A fluorescent dye, FEB, with high fluorescence quantum yield for tumour imaging is reported. FEB dyes can be efficiently synthesized in three steps and then easily modified with either PEG or PEG-iRGD to yield FEB-2000 or FEB-2000-iRGD, respectively. Both modified dyes showed negligible toxicity and were thus able to be adopted for in vivo tumour imaging. PEG modification endowed the dye FEB-2000 with both long circulating times and good tumour targeting properties in a MDA-MB-231 xenograft model. Further conjugation with iRGD to generate FEB-2000-iRGD showed minimal targeting enhancement...
September 1, 2017: Chemical Science
Yuanyuan Yang, Xuefeng Wang, Guochao Liao, Xiqiang Liu, Qiling Chen, Hongmei Li, Ling Lu, Peng Zhao, Zhiqiang Yu
Carbon nanodots (CDs) have been exhibiting increasing applications owing to their luminescence properties and biocompatibility as imaging probes in diagnosis. However, poor tumor targeting and penetration of CDs is still the biggest challenge limiting their tumor imaging efficacy. To improve the tumor targeting and penetration efficiency of CDs, we developed an active tumor targeting imaging system by simply fabricating a tumor-homing penetration peptide iRGD (CRGDKGPDC) to red shift emissive CDs (iRGD-CDs) with a physical method...
September 6, 2017: Journal of Colloid and Interface Science
Xiangsheng Liu, Jinhong Jiang, Andre E Nel, Huan Meng
We demonstrated that activated transcytosis is a major mechanism to complement the classic enhanced permeability and retention effect in pancreatic cancer. This was achieved by using an iRGD peptide that triggers transcytosis pathway at the tumor site. Co-administration of unconjugated iRGD substantially improved the effect of the chemotherapeutics delivering nanocarrier, and resulted in survival improvement in mice. Since the iRGD effect is commensurate with neuropilin-1 expression on tumor vasculature, it is necessary to contemplate a personalized approach to implement this technology...
2017: Molecular & Cellular Oncology
Xiangyou Liu, Gary B Braun, Mingde Qin, Erkki Ruoslahti, Kazuki N Sugahara
In vivo tumor imaging with nanoprobes suffers from poor tumor specificity. Here, we introduce a nanosystem, which allows selective background quenching to gain exceptionally tumor-specific signals. The system uses near-infrared quantum dots and a membrane-impermeable etchant, which serves as a cation donor. The etchant rapidly quenches the quantum dots through cation exchange (ionic etching), and facilitates renal clearance of metal ions released from the quantum dots. The quantum dots are intravenously delivered into orthotopic breast and pancreas tumors in mice by using the tumor-penetrating iRGD peptide...
August 24, 2017: Nature Communications
Dokyoung Kim, Jinyoung Kang, Taejun Wang, Hye Gun Ryu, Jonathan M Zuidema, Jinmyoung Joo, Muwoong Kim, Youngbuhm Huh, Junyang Jung, Kyo Han Ahn, Ki Hean Kim, Michael J Sailor
A major obstacle in luminescence imaging is the limited penetration of visible light into tissues and interference associated with light scattering and autofluorescence. Near-infrared (NIR) emitters that can also be excited with NIR radiation via two-photon processes can mitigate these factors somewhat because they operate at wavelengths of 650-1000 nm where tissues are more transparent, light scattering is less efficient, and endogenous fluorophores are less likely to absorb. This study presents photolytically stable, NIR photoluminescent, porous silicon nanoparticles with a relatively high two-photon-absorption cross-section and a large emission quantum yield...
August 21, 2017: Advanced Materials
Sweta K Gupta, Elisa A Torrico Guzmán, Samantha A Meenach
Three-dimensional (3 D) cell culture platforms are increasingly being used in cancer research and drug development since they mimic avascular tumors in vitro. In this study, we focused on the development of a novel air-grown multicellular spheroid (MCS) model to mimic in vivo tumors for understanding lung cancer biology and improvement in the evaluation of aerosol anticancer therapeutics. 3 D MCS were formed using A549 lung adenocarcinoma cells, comprising cellular heterogeneity with respect to different proliferative and metabolic gradients...
November 15, 2017: International Journal of Cancer. Journal International du Cancer
Tingting Wang, Dangge Wang, Jianping Liu, Bing Feng, Fangyuan Zhou, Hanwu Zhang, Lei Zhou, Qi Yin, Zhiwen Zhang, Zhonglian Cao, Haijun Yu, Yaping Li
The success of cancer chemotherapy is impeded by poor drug delivery efficiency due to the existence of a series of pathophysiological barriers in the tumor. In this study, we reported a tumor acidity-triggered ligand-presenting (ATLP) nanoparticle for cancer therapy. The ATLP nanoparticles were composed of an acid-responsive diblock copolymer as a sheddable matrix and an iRGD-modified polymeric prodrug of doxorubicin (iPDOX) as an amphiphilic core. A PEG corona of the polymer matrix protected the iRGD ligand from serum degradation and nonspecific interactions with the normal tissues while circulating in the blood...
September 13, 2017: Nano Letters
Lijun Ma, Qiubing Chen, Panpan Ma, Moon Kwon Han, Zhigang Xu, Yuejun Kang, Bo Xiao, Didier Merlin
AIM: To enhance the tumor accumulation and targeted drug delivery for colon cancer therapy, iRGD peptide was introduced to the surface of PEGylated camptothecin-loaded nanoparticles (NPs). METHODS: Cellular uptake, targeting specificity, biodistribution and antitumor capacity were evaluated. RESULTS: The functionalization of iRGD facilitated tumor accumulation and cellular uptake of NPs by Colon-26 cells. Furthermore, the resultant iRGD-PEG-NPs remarkably improved the therapeutic efficacy of camptothecin in vitro and in vivo by inducing a higher degree of tumor cell apoptosis compared with PEG-NPs...
August 2017: Nanomedicine
Li Zhang, Yanfeng Xing, Qi Gao, Xuejun Sun, Di Zhang, Gang Cao
Gastric cancer is one of the most of common cancers in the world. 5-Fluorouracil (5-FU) has been identified as one of the standard first-line chemotherapy drugs for locally advanced or metastatic gastric cancer. However, poor tumor penetration, bad selectivity and toxic side effects are the major limitations for the application of chemotherapy drugs in anticancer therapy. Recently, plenty of studies demonstrate that the novel tumor-homing peptide iRGD could promote the tumor-penetrating capability of chemotherapy drugs in multiple cancers, and neuropilin-1 (NRP1) protein is the critical mediator for iRGD...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Xiaoding Xu, Phei Er Saw, Wei Tao, Yujing Li, Xiaoyuan Ji, Sushant Bhasin, Yanlan Liu, Dana Ayyash, Jonathan Rasmussen, Marc Huo, Jinjun Shi, Omid C Farokhzad
The application of nanoparticles (NPs) to drug delivery has led to the development of novel nanotherapeutics for the treatment of various diseases including cancer. However, clinical use of NP-mediated drug delivery has not always translated into improved survival of cancer patients, in part due to the suboptimal properties of NP platforms, such as premature drug leakage during preparation, storage, or blood circulation, lack of active targeting to tumor tissue and cells, and poor tissue penetration. Herein, an innovative reactive oxygen species (ROS)-responsive polyprodrug is reported that can self-assemble into stable NPs with high drug loading...
September 2017: Advanced Materials
Jeffrey D Bjorge, Andy Pang, Donald J Fujita
RNA interference has been used to dissect the importance of individual gene products in various human disease processes, including cancer. Small-interfering RNA, or siRNA, is one of the tools utilized in this regard, but specially-designed delivery agents are required to allow the siRNA to gain optimal access to the cell interior. Our laboratory has utilized two different siRNA-binding delivery peptides containing a polyarginine core, and modified by myristoylation and targeting motifs (iRGD or Lyp-1). A third peptide was designed to assist with endosomal release...
2017: PloS One
Fei Yan, Song Wang, Wei Yang, S Nahum Goldberg, Hao Wu, Wan-Lu Duan, Zhi-Ting Deng, Hai-Bo Han, Hai-Rong Zheng
Purpose To investigate the role of a tumor-penetrating peptide (internalizing CRGDRGPDC [iRGD])-integrated thermally sensitive liposomal (TSL) doxorubicin (DOX) in combination with radiofrequency (RF) ablation of liver tumors in an animal model. Materials and Methods Approval from the institutional animal care and use committee was obtained. Characterization of iRGD-TSL-DOX was performed in vitro. Next, H22 liver adenocarcinomas were implanted in 138 mice in vivo. The DOX accumulation and cell apoptosis of iRGD-TSL-DOX and TSL-DOX with or without RF were evaluated (n = 5) at different time points after treatment with quantitative analysis or pathologic staining...
November 2017: Radiology
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