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Simona Camorani, Billy Samuel Hill, Francesca Collina, Sara Gargiulo, Maria Napolitano, Monica Cantile, Maurizio Di Bonito, Gerardo Botti, Monica Fedele, Antonella Zannetti, Laura Cerchia
While the overall mortality for breast cancer has recently declined, management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and the lack of targeted therapies. Genomic profiling studies highlighted the high level of heterogeneity of this cancer, which comprises different subtypes with unique phenotypes and response to treatment. Platelet-derived growth factor receptor β (PDGFRβ) is an established mesenchymal/stem cell-specific marker in human glioblastoma and, as recently suggested, it may uniquely mark breast cancer cells with stem-like characteristics and/or that have undergone epithelial-mesenchymal transition...
2018: Theranostics
Yutong He, Genlan Ye, Chen Song, Chuangkun Li, Weirong Xiong, Lei Yu, Xiaozhong Qiu, Leyu Wang
The controversy between polypyrrole's (Ppy) biocompatibility and its aggregation on nanofibers impedes application of conductive Ppy-incorporated nanofibers to create engineered cardiac microenvironments. The purpose of this study was to fabricate a functional scaffold for engineering cardiac patches (ECP) using a high concentration of methyl acrylic anhydride-gelatin (GelMA)-Ppy nanoparticles, mussel-inspired crosslinker, and electrospun (ES)-GelMA/polycaprolactone (PCL) nanofibrous membrane. Methods: First, spherical GelMA-Ppy nanoparticles were obtained when the methacrylate groups of GelMA formed a self-crosslinked network through oxidative polymerization of Ppy...
2018: Theranostics
Zhanyao Tan, Kun Chen, Wenjiao Wu, Yanqing Zhou, Jinrong Zhu, Geyan Wu, Lixue Cao, Xin Zhang, Hongyu Guan, Yi Yang, Wei Zhang, Jun Li
High levels of angiogenesis are associated with poor prognosis in patients with gliomas. However, the molecular mechanisms underlying tumor angiogenesis remain unclear. Methods: The effect of homeobox C10 (HOXC10) on tube formation, migration, and proliferation of human umbilical vein endothelial cells (HUVECs) and on chicken chorioallantoic membranes (CAMs) was examined. An animal xenograft model was used to examine the effect of HOXC10 on xenograft angiogenesis or the effect of bevacizumab, a monoclonal antibody against vascular endothelial growth factor A (VEGFA), on HOXC10-overexpressing xenografts...
2018: Theranostics
Jennifer Wischhusen, Katheryne E Wilson, Jean-Guy Delcros, Rodolfo Molina-Peña, Benjamin Gibert, Shan Jiang, Jacqueline Ngo, David Goldschneider, Patrick Mehlen, Juergen K Willmann, Frederic Padilla
In ultrasound molecular imaging (USMI), ligand-functionalized microbubbles (MBs) are used to visualize vascular endothelial targets. Netrin-1 is upregulated in 60% of metastatic breast cancers and promotes tumor progression. A novel netrin-1 interference therapy requires the assessment of netrin-1 expression prior to treatment. In this study, we studied netrin-1 as a target for USMI and its potential as a companion diagnostic in breast cancer models. Methods: To verify netrin-1 expression and localization, an in vivo immuno-localization approach was applied, in which anti-netrin-1 antibody was injected into living mice 24 h before tumor collection, and revealed with secondary fluorescent antibody for immunofluorescence analysis...
2018: Theranostics
Sarah M Cheal, Hong Xu, Hong-Fen Guo, Mitesh Patel, Blesida Punzalan, Edward K Fung, Sang-Gyu Lee, Meghan Bell, Manisha Singh, Achim A Jungbluth, Pat B Zanzonico, Alessandra Piersigilli, Steven M Larson, Nai-Kong V Cheung
In recent reports, we have shown that optimized pretargeted radioimmunotherapy (PRIT) based on molecularly engineered antibody conjugates and 177 Lu-DOTA chelate (DOTA-PRIT) can be used to cure mice bearing human solid tumor xenografts using antitumor antibodies to minimally internalizing membrane antigens, GPA33 (colon) and GD2 (neuroblastoma). However, many solid tumor membrane antigens are internalized after antibody binding and it is generally believed that internalizing tumor membrane antigens are not suitable targets for PRIT...
2018: Theranostics
Lei Hua, Zhen Wang, Liang Zhao, Honglin Mao, Guanghui Wang, Kairuo Zhang, Xuejiao Liu, Dongmei Wu, Yuanlin Zheng, Jun Lu, Rutong Yu, Hongmei Liu
Treatment of malignant glioma is a challenge facing cancer therapy. In addition to surgery, and chemotherapy, radiotherapy (RT) is one of the most effective modalities of glioma treatment. However, there are two crucial challenges for RT facing malignant glioma therapy: first, gliomas are known to be resistant to radiation due to their intratumoral hypoxia; second, radiosensitizers may exhibit a lack of target specificity, which may cause a lower concentration of radiosensitizers in tumors and toxic side effects in normal tissues...
2018: Theranostics
Qiqing Sun, Bo Zhang, Qiangsheng Hu, Yi Qin, Wenyan Xu, Wensheng Liu, Xianjun Yu, Jin Xu
Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most challenging lethal tumors and has a very poor prognosis. In addition to cancer cells, the tumor microenvironment created by a repertoire of resident and recruited cells and the extracellular matrix also contribute to the acquisition of hallmarks of cancer. Among these factors, cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment. CAFs originate from the activation of resident fibroblasts and pancreatic stellate cells, the differentiation of bone marrow-derived mesenchymal stem cells and epithelial-to-mesenchymal transition...
2018: Theranostics
Huan Liang, Zhanwei Zhou, Renjie Luo, Mangmang Sang, Bowen Liu, Minjie Sun, Wei Qu, Feng Feng, Wenyuan Liu
Photodynamic therapy relies on photosensitizers to generate cytotoxic reactive oxygen species (ROS) resulting in the apoptois of tumor cells. However, there is an antioxidant system that impedes the elevation of oxidation levels in tumor cells. Thus, photodynamic therapy may exhibit insufficient curative effects due to ungenerous reactive oxygen species levels. Herein, we describe tumor-specific activated photodynamic therapy using an oxidation-regulating strategy. Methods: We first synthesised a reactive oxygen species-sensitive amphipathic prodrug of gambogic acid-grafted hyaluronic acid (HA-GA)...
2018: Theranostics
Jiaju Lu, Xuezhen Shen, Xun Sun, Heyong Yin, Shuhui Yang, Changfeng Lu, Yu Wang, Yifan Liu, Yingqi Huang, Zijin Yang, Xianqi Dong, Chenhao Wang, Quanyi Guo, Lingyun Zhao, Xiaodan Sun, Shibi Lu, Antonios G Mikos, Jiang Peng, Xiumei Wang
Even small cartilage defects could finally degenerate to osteoarthritis if left untreated, owing to the poor self-healing ability of articular cartilage. Stem cell transplantation has been well implemented as a common approach in cartilage tissue engineering but has technical complexity and safety concerns. The stem cell homing-based technique emerged as an alternative promising therapy for cartilage repair to overcome traditional limitations. In this study, we constructed a composite hydrogel scaffold by combining an oriented acellular cartilage matrix (ACM) with a bone marrow homing peptide (BMHP)-functionalized self-assembling peptide (SAP)...
2018: Theranostics
Muhammad Suhaeri, Mi Hee Noh, Ji-Hoi Moon, In Gul Kim, Seung Ja Oh, Sang Su Ha, Jong Ho Lee, Kwideok Park
Skin injuries are frequently encountered in daily life, but deep wounds often poorly self-heal and do not recover completely. In this study, we propose a novel skin patch that combines antibiotic, cell-derived extracellular matrix (ECM) and biocompatible polyvinyl alcohol (PVA) hydrogel. Methods: Decellularized human lung fibroblast-derived matrix (hFDM) was prepared on tissue culture plate (TCP) and PVA solution was then poured onto it. After a freeze-thaw process, PVA was peeled off from TCP along with hFDM tightly anchored to PVA...
2018: Theranostics
Christian J Konopka, Marcin Wozniak, Jamila Hedhli, Agata Ploska, Aaron Schwartz-Duval, Anna Siekierzycka, Dipanjan Pan, Gnanasekar Munirathinam, Iwona T Dobrucki, Leszek Kalinowski, Lawrence W Dobrucki
The receptor for advanced glycation end-products (RAGE) is central to multiple disease states, including diabetes-related conditions such as peripheral arterial disease (PAD). Despite RAGE's importance in these pathologies, there remains a need for a molecular imaging agent that can accurately assess RAGE levels in vivo . Therefore, we have developed a multimodal nanoparticle-based imaging agent targeted at RAGE with the well-characterized RAGE ligand, carboxymethyllysine (CML)-modified human serum albumin (HSA)...
2018: Theranostics
Zhi Huang, Wei Zhou, Yongtao Li, Mei Cao, Tianqi Wang, Yakun Ma, Qingxiang Guo, Xin Wang, Chao Zhang, Chenglan Zhang, Wenzhi Shen, Yanhua Liu, Yanan Chen, Jianyu Zheng, Shengyong Yang, Yan Fan, Rong Xiang
Despite initial progress in preclinical models, most known histone deacetylase inhibitors (HDACis) used as a single agent have failed to show clinical benefits in nearly all types of solid tumours. Hence, the efficacy of HDACis in solid tumours remains uncertain. Herein, we developed a hybrid HDAC inhibitor that sensitized solid tumours to HDAC-targeted treatment. Methods: A hybrid molecule, Roxyl-zhc-84 was designed and synthesized with novel architecture. The pharmacokinetics and toxicity of Roxyl-zhc-84 were analysed...
2018: Theranostics
Anais Moyon, Philippe Garrigue, Laure Balasse, Samantha Fernandez, Pauline Brige, Marie Nollet, Guillaume Hache, Marcel Blot-Chabaud, Françoise Dignat-George, Benjamin Guillet
This study aimed to develop a PET imaging agent of angiomotin (AMOT) expression, a potential biomarker of functional tissue regeneration in post-ischaemic conditions. Methods: Hindlimb ischaemia was induced by ligature and resection of the right femoral artery in mice, and clinical score and limb perfusion were evaluated up to 30 days after surgery. AMOT expression was evaluated by histology and Western blot analysis. NODAGA-conjugates of AMOT ligand, sCD146, were designed, synthesised and radiolabelled with gallium-68...
2018: Theranostics
Huan Wang, Yang Yang, Xin Sun, Fang Tian, Shuyuan Guo, Wei Wang, Zhen Tian, Hong Jin, Zhiguo Zhang, Ye Tian
In advanced atherosclerotic plaques, defective efferocytosis of apoptotic foam cells and decreased cholesterol efflux contribute to lesion progression. In our previous study, we demonstrated that 5-aminolevulinic acid (ALA)-mediated sonodynamic therapy (SDT) could induce foam cells apoptosis via the mitochondrial-caspase pathway. In the current research, we sought to explore ALA-SDT-induced apoptosis of phagocytes and the effects of cholesterol efflux and efferocytosis in advanced apoE-/- mice plaque. Methods: apoE-/- mice fed western diet were treated with ALA-SDT and sacrificed at day 1, day 3, day 7 and day 28 post treatment...
2018: Theranostics
Matthias Brendel, Anna Jaworska, Felix Overhoff, Tanja Blume, Federico Probst, Franz-Josef Gildehaus, Peter Bartenstein, Christian Haass, Bernd Bohrmann, Jochen Herms, Michael Willem, Axel Rominger
Beta secretase (BACE) inhibitors are promising therapeutic compounds currently in clinical phase II/III trials. Preclinical [18 F]-florbetaben (FBB) amyloid PET imaging facilitates longitudinal monitoring of amyloidosis in Alzheimer's disease (AD) mouse models. Therefore, we applied this theranostic concept to investigate, by serial FBB PET, the efficacy of a novel BACE1 inhibitor in the PS2APP mouse, which is characterized by early and massive amyloid deposition. Methods: PS2APP and C57BL/6 (WT) mice were assigned to treatment (PS2APP: N=13; WT: N=11) and vehicle control (PS2APP: N=13; WT: N=11) groups at the age of 9...
2018: Theranostics
Dong Wang, Michelle Mei Suet Lee, Wenhan Xu, Ryan Tsz Kin Kwok, Jacky Wing Yip Lam, Ben Zhong Tang
The utilization of luminogens with aggregation-induced emission (AIE) characteristics has recently been developed at a tremendous pace in the area of theranostics, mainly because AIE luminogens (AIEgens) hold various distinct advantages, such as good biocompatibility, excellent fluorescence properties, simple preparation and modification, perfect size of nano-aggregation for enhanced permeability and retention effect, promoted efficiencies of photodynamic and photothermal therapies, efficient photoacoustic imaging, and ready constructions of multimodal imaging and therapy...
2018: Theranostics
Qi-Long Wang, XiaoYing Zhuang, Mukesh K Sriwastva, Jingyao Mu, Yun Teng, Zhongbin Deng, Lifeng Zhang, Kumaran Sundaram, Anil Kumar, Donald Miller, Jun Yan, Huang-Ge Zhang
Tumor-specific delivery of therapeutics is challenging. One of the major hurdles for successfully delivering targeted agents by nanovectors is the filtering role of the liver in rapidly sequestering nanovectors from the circulation. Exosomes, a type of endogenous nanoparticle, circulate continuously in the peripheral blood and play a role in intercellular communication. The aim of this study was to determine whether the level of endogenous exosomes has an effect on nanovector delivery efficiency of targeted agents...
2018: Theranostics
Zaigang Zhou, Baoli Zhang, Haoran Wang, Ahu Yuan, Yiqiao Hu, Jinhui Wu
Tumors are usually hypoxic, which limits the efficacy of current tumor therapies, especially radiotherapy in which oxygen is essential to promote radiation-induced cell damage. Herein, by taking advantage of the ability of perfluorocarbon (PFC) to promote red blood cell penetration, we developed a simple but effective two-stage oxygen delivery strategy to modulate the hypoxic tumor microenvironment using PFC nanoparticles. Methods: We first examined the two-stage oxygen delivery ability of PFC nanoparticles on relieving tumor hypoxia through platelet inhibition...
2018: Theranostics
Xi He, Jinxiao Zhang, Chao Li, Yu Zhang, Yifei Lu, Yujie Zhang, Lisha Liu, Chunhui Ruan, Qinjun Chen, Xinli Chen, Qin Guo, Tao Sun, Jianjun Cheng, Chen Jiang
Efficient drug accumulation in tumor is essential for chemotherapy. We developed redox-responsive diselenide-based high-loading prodrug nanoparticles (NPs) for targeted triple negative breast cancer (TNBC) treatment. Method: Redox-responsive diselenide bond (Se-Se) containing dimeric prodrug (PTXD-Se) was synthesized and co-precipitated with TNBC-targeting amphiphilic copolymers to form ultra-stable NPs (uPA-PTXD NPs). The drug loading capacity and redox-responsive drug release behavior were studied. TNBC targeting effect and anti-tumor effect were also evaluated in vitro and in vivo...
2018: Theranostics
Mingxi Li, Yang Liu, Jinpeng Chen, Taotao Liu, Zhuxiao Gu, Jianqiong Zhang, Xiaochun Gu, Gaojun Teng, Fang Yang, Ning Gu
Since the expected therapeutic results of ischemic stroke are strictly time dependent, early and accurate diagnosis as well as short intervals between diagnosis and treatment are key factors for the survival of stroke patients. In this study, we fabricated platelet (PLT) membrane-derived biomimetic nanobubbles (PNBs) for timely perfusion intervention and ultrasound imaging of acute ischemic stroke. Methods: The PNBs are fabricated by sonication-assisted reassembly of repeatedly freeze-thawed live platelet-derived PLT membrane vesicles (PMVs)...
2018: Theranostics
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