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Jun-Qing Situ, Xiao-Juan Wang, Xiu-Liang Zhu, Xiao-Ling Xu, Xu-Qi Kang, Jing-Bo Hu, Chen-Ying Lu, Xiao-Ying Ying, Ri-Sheng Yu, Jian You, Yong-Zhong Du
Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 μg. mL(-1) and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI...
October 24, 2016: Scientific Reports
Shaghayegh Fathi, Adegboyega K Oyelere
Liposomes are biodegradable and biocompatible self-forming spherical lipid bilayer vesicles. They can encapsulate and deliver one or more hydrophobic and hydrophilic therapeutic agents with poor therapeutic indices to tumor sites. Properties such as lipid bilayer fluidity, charge, size and surface hydration can be modified to extend liposome circulation time in the bloodstream and enhance efficacy. The focus of this review is on ligand-conjugated liposomes and their potential application in tumor-targeted delivery...
October 24, 2016: Future Medicinal Chemistry
Dongxiao Wang, Wanxian Luo, Ge Wen, Li Yang, Shaofu Hong, Shiyu Zhang, Jianxin Diao, Jianguo Wang, Hongqin Wei, Yingjia Li, Ying Wang
We have fabricated a negative-charged nanoparticle (Heparin-Folate-Tat-Taxol NP, H-F-Tat-T NP) with dual ligands, tumor targeting ligand folate and cell-penetrating peptide Tat, to deliver taxol presenting great anticancer activity for sensitive cancer cells, while it fails to overcome multidrug resistance (MDR) in MCF-7/T cells (taxol-resistant breast cancer cells). Ultrasound (US) can increase the sensitivity of positive-charged NPs thereby making it possible to reverse MDR through inducing NPs' drug release...
January 2017: Ultrasonics Sonochemistry
Zhan Zhou, Yuhui Zheng, Cheng Zhang Cheng, Jiajia Wen, Qianming Wang
Here we developed the first case of pyropheophorbide-a-loaded PEGylated-hybrid carbon nanohorns (CNH-Pyro) to study tumor targeting therapy. During incubation with living cells, CNH-Pyro exhibited very intense red emissions. The intracellular imaging results were carried out by flow cytometry based on four different kinds of cell lines (including three adherent cell lines and one suspension cell line). Compared with free pyropheophorbide-a, CNH-Pyro demonstrated enhanced photodynamic tumor ablation efficiency during in vitro experiments due to improved biocompatibility of the hybrid nanomaterial and the photothermal therapy effect derived from carbon-network structure...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Xiao-Bin Fang, Ying-Qi Xu, Hon-Fai Chan, Chun-Ming Wang, Qing Zheng, Fei Xiao, Mei-Wan Chen
Hepatocellular carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer death worldwide. Most current therapeutic agents lack the tumor-targeting efficiency and result in a nonselective biodistribution in the body. In our previous study, we identified a peptide Ala-Pro-Asp-Thr-Lys-Thr-Gln (APDTKTQ) that can selectively bind to the receptor of advanced glycation end-products (RAGE), an immunoglobulin superfamily cell surface molecule overexpressed during HCC malignant progression. Here, we report the design of a mixed micelles system modified with this peptide to target HCC cells...
October 21, 2016: Molecular Pharmaceutics
Yun-Wen Yang, Chun-Mei Zhang, Xian-Jie Huang, Xiao-Xin Zhang, Lin-Kai Zhang, Jia-Huang Li, Zi-Chun Hua
Fas-associated protein with death domain (FADD), a pivotal adaptor protein transmitting apoptotic signals, is indispensable for the induction of extrinsic apoptosis. However, overexpression of FADD can form large, filamentous aggregates, termed death effector filaments (DEFs) by self-association and initiate apoptosis independent of receptor cross-linking. A mutant of FADD, which is truncated of the C-terminal tail (m-FADD, 182-205 aa) named N-FADD (m-FADD, 1-181 aa), can dramatically up-regulate the strength of FADD self-association and increase apoptosis...
October 21, 2016: Scientific Reports
Marc Jansen, Sophie Em Veldhuijzen van Zanten, Dannis G Van Vuurden, Marc Huisman, Danielle J Vugts, Otto S Hoekstra, Guus A M S van Dongen, Gert-Jan Jl Kaspers
: Predictive tools to guide therapy in children with brain tumors are urgently needed. We introduced molecular imaging to facilitate this. We investigated whether bevacizumab can reach the tumor in children with diffuse intrinsic pontine glioma (DIPG) by measuring the tumor uptake of zirconium-89((89)Zr)-labeled bevacizumab by PET. In addition we evaluated the safety of the procedure in children and determined the optimal timing of imaging. METHODS: Patients received 0...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
E Böhmová, R Pola
A tumor-targeting drug delivery system consists of a tumor recognition moiety and a directly linked cytotoxic agent or an agent attached to a water-soluble synthetic polymer carrier through a suitable linker. Conjugation of a drug with a polymer carrier can change its solubility, toxicity, biodistribution, blood clearance and therapeutic specificity. Increased therapeutic specificity of a polymer drug can be achieved by the attachment of a targeting moiety (e.g. a lectin, protein, antibody, or peptide) that specifically interacts with receptors on the target cells...
October 20, 2016: Physiological Research
Yang Li, Hebin Wang, Kai Wang, Qinglian Hu, Qi Yao, Youqing Shen, Guocan Yu, Guping Tang
A new type of tumor-targeted nanovehicle peptide-conjugated PSPG (PSPGP) is successfully synthesized for co-delivery of paclitaxel (PTX) and TR3 small interfering RNA (siRNA). In vitro and in vivo investigations demonstrate that the redox-responsive PSPGP exhibit enhanced endosomal escape and intracellular degradation, which facilitate PTX and TR3 siRNA release, effectively improving the antitumor efficacy.
October 20, 2016: Small
Man Kyu Shim, Hong Yeol Yoon, Ju Hee Ryu, Heebeom Koo, Sangmin Lee, Jae Hyung Park, Jong-Ho Kim, Seulki Lee, Martin G Pomper, Ick Chan Kwon, Kwangmeyung Kim
Recently, metabolic glycoengineering with bioorthogonal click reactions has focused on improving the tumor targeting efficiency of nanoparticles as delivery vehicles for anticancer drugs or imaging agents. It is the key technique for developing tumor-specific metabolic precursors that can generate unnatural glycans on the tumor-cell surface. A cathepsin B-specific cleavable substrate (KGRR) conjugated with triacetylated N-azidoacetyl-d-mannosamine (RR-S-Ac3 ManNAz) was developed to enable tumor cells to generate unnatural glycans that contain azide groups...
October 20, 2016: Angewandte Chemie
Tetsushi Kubota, Shinji Kuroda, Toshiaki Morihiro, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara
Trastuzumab(Tmab)is a humanized monoclonalantibody that binds to the human epidermalgrowth factor receptor 2 (HER2). It is clinically used for HER2-positive breast and gastric cancers; however, the use of Tmab is restricted to tumors expressing high levels of HER2(accounting for only 20%of tumors), and Tmab cannot be used for tumors resistant to Tmab. Although novel HER2-targeted agents have been developed to treat Tmab-resistant tumors, none of these have shown clinical efficacy in gastric cancer patients...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Ji Woong Lee, Yong Jin Lee, Un Chol Shin, Suhng Wook Kim, Byung Il Kim, Kyo Chul Lee, Jung Young Kim, Ji-Ae Park
Improving the in vivo pharmacokinetics (PK) of positron emission tomography (PET) radiotracers is of critical importance to tumor diagnosis and therapy. In the case of peptide-based radiotracers, the modification and addition of a linker or spacer functional group often offer faster in vivo pharmacokinetic behavior. In this study, the authors introduced two new PEGlyated dimeric c(RGD-ACH-K) conjugates, in which an aminocyclohexane carboxylic acid (ACH) is inserted into the ring chain of the cyclic RGD peptides, with a common bifunctional chelator (DOTA or NOTA) used for labeling with radiometals (including (68)Ga and (64)Cu)...
October 2016: Cancer Biotherapy & Radiopharmaceuticals
Saeed Zavareh, Milad Mahdi, Soheyla Erfanian, Hamid Hashemi-Moghaddam
PURPOSE: Carrier-mediated drug delivery systems can be used to increase the intracellular concentration of drugs in cancerous cells, thereby improving drug biodistribution and minimizing unwanted side effects. This study aimed to investigate the effect of synthesized magnetic molecularly imprinted polydopamine for controlled doxorubicin (DOX) delivery in a breast adenocarcinoma model of BALB/c mice with an external magnetic field. METHODS: The synthesized DOX-imprinted polydopamine (DOX-IP) was characterized using Fourier transform infrared spectroscopy and scanning electron microscopy...
October 17, 2016: Cancer Chemotherapy and Pharmacology
Guangming Gong, Wenya Liu, Shudong Wang
This study aimed to reduce the cytotoxicity and improve the targeting of aclacinomycin (ACM) by covalently coupling it with amino-oxyacetic acid (AOA) to generate an active intermediate, AOA-ACM. AOA-ACM was conjugated with self-assembled human serum albumin (HSA) nanoparticles constructed using tris(2-carboxyethyl)phosphine (TCEP) as disulfide bond breaking molecules in an 'opening stage-intermediate-closing stage' route, in which the hydrophobic interaction, interchange of sulfhydryl and hydrogen bond may be the key factors in the assembling process...
October 17, 2016: Nanotechnology
Qing Chang, Rui Geng, Shanzheng Wang, Ding Qu, Xiangfei Kong
Treatment for multiple myeloma (MM) with a combined strategy of bone and tumor targeting remains a crucial technical challenge due to the incorporation of various functional components into one single system. Here, we developed dioleoyl phosphatidic acid (DOPA)-based paclitaxel (PTX)-loaded liposomes with modifications of alendronate and transferrin (Ald-/Tf-modified PTX-L), which were capable of bone affinity mediated by phosphate groups in DOPA and alendronate, and tumor targeting offered by transferrin. Ald-/Tf-modified PTX-L had clear and well-defined spherical shape with an intermediated size of 118...
October 17, 2016: Drug Delivery
Elham Ajorlou, Ahmad Yari Khosroushahi
PURPOSE: The dawn of the state-of-the-art methods of cancer treatments, nano-based delivery systems, has dispensed with the mainstream chemotherapy for being inadequate in yielding productive results and the numerous reported side effects. The popularity of this complementary approach in the course of the last two decades has been primarily attributed to its capacity to elevate the therapeutic index of anticancer drugs as well as removing the impassable delivery barriers in solid tumors with the minimal damage to the normal tissues...
October 15, 2016: Cancer Chemotherapy and Pharmacology
Dan Ishihara, Laurentiu Pop, Tsuguhide Takeshima, Puneeth Iyengar, Raquibul Hannan
Cancer immunotherapy exploits the immune system's ability to differentiate between tumor target cells and host cells. Except for limited success against a few tumor types, most immunotherapies have not achieved the desired clinical efficacy until recently. The field of cancer immunotherapy has flourished with a variety of new agents for clinical use, and remarkable progress has been made in the design of effective immunotherapeutic regimens. Furthermore, the therapeutic outcome of these novel agents is enhanced when combined with conventional cancer treatment modalities including radiotherapy (RT)...
October 14, 2016: Cancer Immunology, Immunotherapy: CII
Amr S Abu Lila, Masakazu Fukushima, Cheng-Long Huang, Hiromi Wada, Tatsuhiro Ishida
Pemetrexed (PMX) is a key drug for the treatment of malignant pleural mesothelioma (MPM). However, its therapeutic efficacy is cruelly restricted in many clinical settings by the over-expression of thymidylate synthase (TS) gene. Recently, we emphasized the efficacy of locally administered shRNA designed against TS gene in enhancing the cytotoxic effect of PMX against orthotopically implanted MPM cells in tumor xenograft tumor model. In the present study, we investigated the efficacy of systemic, rather than local, delivery of TS RNAi molecule in sensitizing MPM cells to the cytotoxic effect of PMX...
October 14, 2016: Molecular Pharmaceutics
Meng-Qing Gong, Cong Wu, Xiao-Yan He, Jing-Yi Zong, Jin-Long Wu, Ren-Xi Zhuo, Si-Xue Cheng
PURPOSE: To overcome multi-drug resistance (MDR) in tumor chemotherapy, a polymer/inorganic hybrid drug delivery platform with tumor targeting property and enhanced cell uptake efficiency was developed. METHOD: To evaluate the applicability of our delivery platform for the delivery of different drug resistance inhibitors, two kinds of dual-drug pairs (doxorubicin/buthionine sulfoximine and doxorubicin/tariquidar, respectively) were loaded in heparin-biotin/heparin/protamine sulfate/calcium carbonate nanovesicles to realize simultaneous delivery of an anticancer drug and a drug resistance inhibitor into drug-resistant tumor cells...
October 13, 2016: Pharmaceutical Research
Hui Liu, Mei Zhao, Jin Wang, Mingpei Pang, Zhenzhou Wu, Liqing Zhao, Zhinan Yin, Zhangyong Hong
Photodynamic therapy (PDT) has many advantages in treating cancers, but the lack of ideal photosensitizers continues to be a major limitation restricting the clinical utility of PDT. This study aimed to overcome this obstacle by generating pyropheophorbide-a-loaded polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles (NPs) for efficient tumor-targeted PDT. The fabricated NPs were efficiently internalized in the mitochondrion by cancer cells, and they efficiently killed cancer cells in a dose-dependent manner when activated with light...
2016: International Journal of Nanomedicine
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