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https://www.readbyqxmd.com/read/29161013/intelligent-peptide-gathering-mechanical-arm-tames-wild-trojan-horse-peptides-for-the-controlled-delivery-of-cancer-nanotherapeutics
#1
Nian-Qiu Shi, Yan Li, Yong Zhang, Nan Shen, Ling Qi, Shu-Ran Wang, Xian-Rong Qi
Cell-penetrating peptides (CPPs), also called "Trojan-Horse" peptides, have been used for facilitating intracellular delivery of numerous diverse cargoes and even nanocarriers. However, the lack of targeting specificity ("wildness" or nonselectivity) of CPP-nanocarriers remains an intractable challenge for many in vivo applications. In this work, we used an intelligent "peptide-gathering mechanical arm" (Int PMA) to curb CPPs' wildness and enhance the selectivity of R9-liposome-based cargo delivery for tumor targeting...
November 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29158362/cd38-bispecific-antibody-pretargeted-radioimmunotherapy-for-multiple-myeloma-and-other-b-cell-malignancies
#2
Damian J Green, Shyril O'Steen, Yukang Lin, Melilssa L Comstock, Aimee L Kenoyer, Donald K Hamlin, D Scott Wilbur, Darrell R Fisher, Margaret Nartea, Mark D Hylarides, Ajay K Gopal, Theodore A Gooley, Johnnie J Orozco, Brian G Till, Kelly D Orcutt, K Dane Wittrup, Oliver W Press
Pretargeted radioimmunotherapy (PRIT) has demonstrated remarkable efficacy targeting tumor antigens, but immunogenicity and endogenous biotin blocking may limit clinical translation. We describe a new PRIT approach for the treatment of Multiple Myeloma (MM) and other B cell malignancies, for which we developed an anti-CD38 bispecific fusion protein that eliminates endogenous biotin interference and immunogenic elements. In murine xenograft models of MM and non-Hodgkin lymphoma (NHL), the CD38 bispecific construct demonstrated excellent blood clearance and tumor targeting...
November 20, 2017: Blood
https://www.readbyqxmd.com/read/29156717/oligomer-procyanidins-f2-repress-hif-1%C3%AE-expression-in-human-u87-glioma-cells-by-inhibiting-the-egfr-akt-mtor-and-mapk-erk1-2-signaling-pathways-in-vitro-and-in-vivo
#3
Hong-Li Zheng, Li-Hui Wang, Bao-Shan Sun, Yi Li, Jing-Yu Yang, Chun-Fu Wu
Hypoxia-inducible factor-1 (HIF-1) is over-expressed in gliomas and has become one of the most compelling tumor targets. In this study, we found that oligomer procyanidins (F2) can suppress the expressions of HIF-1α and its target genes in U87 cells, and also down-regulate the EGFR/PI3K/AKT/mTOR and MAPK/ERK1/2 pathways in vitro and in vivo. Furthermore, hypoxia-induced formation of tubular structures by human umbilical vascular endothelial cells and the migration and invasion of U87 cells could be inhibited by F2 in a HIF-1 dependent manner...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154537/tools-for-pathogen-proteomics-fishing-with-biomimetic-nanosponges
#4
Ute Distler, Stefan Tenzer
The identification of the major virulence factors that drive pathogenicity is critical for gaining insight into the underlying molecular mechanisms of diseases. Although genetic approaches combined with functional analyses have markedly increased the rate of virulence factor discovery, the divergence between genome and proteome can impair the identification of important markers, in particular, of those that act in concert or depend on specific environmental factors. Recently, membrane-coated nanomaterials mimicking source cells of interest have emerged as powerful tools that can be used for improved tumor targeting and as "nanotraps" to capture chemokines and bacterial toxins...
November 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/29154189/novel-theranostic-zinc-phthalocyanine-phospholipid-complex-self-assembled-nanoparticles-for-imaging-guided-targeted-photodynamic-treatment-with-controllable-ros-production-and-shape-assisted-enhanced-cellular-uptake
#5
Jinyuan Ma, Yang Li, Guihua Liu, Ai Li, Yilin Chen, Xinyi Zhou, Dengyue Chen, Zhenqing Hou, Xuan Zhu
The novel drug delivery system based on self-assembly of zinc phthalocyanine-soybean phosphatidylcholine (ZnPc-SPC) complex was developed by a co-solvent method followed by a nanoprecipitaion technique. DSPE-PEG-methotrexate (DSPE-PEG-MTX) was introduced on the surface of ZnPc-SPC self-assembled nanoparticles (ZS) to endow them with folate receptor-targeting property. NMR, XRD, FTIR, and UV-vis-NIR analysis demonstrated the weak molecular interaction between ZnPc and SPC. The ZS functionalized with DSPE-PEG-MTX (ZSPM) was successfully constructed with an average particle size of ∼170nm, a narrow size distribution, and could remain physiologically stable for at least 7days...
October 24, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29151956/strategies-for-bispecific-single-chain-antibody-in-cancer-immunotherapy
#6
REVIEW
Shu-Juan Zhou, Jia Wei, Shu Su, Fang-Jun Chen, Yu-Dong Qiu, Bao-Rui Liu
Genetic engineering has resulted in more than 50 recombinant bispecific antibody formats over the past two decades. Bispecific scFv antibodies represent a successful and promising immunotherapy platform that retargets cytotoxic T cells to tumor cells, with one scFv directed to tumor-associated antigens and the other to T cells. Based on this antibody construct, strategies for both specific tumor targeting and T cell activation are reviewed here. Three distinct types of tumor antigens are considered to optimize specificity and safety in bispecific scFv based treatment: cancer-testis antigens, neo-antigens and virus-associated antigens...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29142997/advanced-smart-photosensitizers-for-more-effective-cancer-treatment
#7
Wooram Park, Soojeong Cho, Jieun Han, Heejun Shin, Kun Na, Byeongdu Lee, Dong-Hyun Kim
Photodynamic therapy (PDT) based upon the use of light and photosensitizers (PSs) has been used as a novel treatment approach for a variety of tumors. It, however, has several major limitations in the clinic: poor water solubility, long-term phototoxicity, low tumor targeting efficacy, and limited light penetration. With advances in nanotechnology, materials science, and clinical interventional imaging procedures, various smart-PSs have been developed for improving their cancer-therapeutic efficacy while reducing the adverse effects...
November 16, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29141148/plasmonically-enhanced-galactoxyloglucan-endowed-gold-nanoparticles-exposed-tumor-targeting-biodistribution-envisaged-in-a-surface-enhanced-raman-scattering-platform
#8
Manu M Joseph, Jyothi B Nair, Kaustabh Kumar Maiti, Sreelekha Therakathinal T
Biopolymer capped gold nanoparticles (AuNPs) were perceived for tracing biodistribution in a solid tumor mice through surface-enhanced Raman scattering (SERS) fingerprinting. In this strategy, a robust and ecofriendly green chemistry approach was adopted to construct galactoxyloglucan (PST001) endowed AuNPs (PST-GNPs) with cancer-cell-selective toxic nature and excellent biocompatibility. Plasmonically enhanced light scattering properties facilitated PST-GNPs to be a superior SERS substrate with high Raman signal enhancement...
November 15, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29139598/preparation-and-comparative-evaluation-of-99m-tc-hynic-cngr-and-99m-tc-hynic-peg2-cngr-as-tumor-targeting-molecular-imaging-probes
#9
Kusum Vats, Drishty Satpati, Rohit Sharma, Chandan Kumar, Haladhar Dev Sarma, Sharmila Banerjee
The tripeptide sequence NGR (asparagine-glycine-arginine) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells as well as tumor vasculature. Thus NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard two NGR peptide ligands, HYNIC-c(NGR) and HYNIC-PEG2 -c(NGR) were synthesized, radiolabeled with (99m) Tc and evaluated in CD13-positive human fibrosarcoma HT-1080 tumor xenografts. The radiotracers, (99m) Tc-HYNIC-c(NGR) and (99m) Tc-HYNIC-PEG2 -c(NGR) could be prepared in ~95% radiochemical purity (RCP) and exhibited excellent in vitro and in vivo stability...
November 15, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29138222/decitabine-enhances-targeting-of-aml-cells-by-cd34-progenitor-derived-nk-cells-in-nod-scid-il2rg-null-mice
#10
Jeannette Cany, Mieke W H Roeven, Janneke S Hoogstad-van Evert, Willemijn Hobo, Frans Maas, Rosalia Franco Fernandez, Nicole M A Blijlevens, Walter J van der Velden, Gerwin Huls, Joop H Jansen, Nicolaas P M Schaap, Harry Dolstra
Combining NK cell adoptive transfer with hypomethylating agents (HMA) is an attractive therapeutic approach for patients with acute myeloid leukemia (AML). However, data regarding the impact of HMA on NK cell functionality are mostly derived from in vitro studies with high non-clinical relevant drug concentrations. Here, we report a comparative study of azacitidine and decitabine in combination with allogeneic NK cells generated from CD34(+) hematopoietic stem and progenitor cells (HSPC-NK cells) in in vitro and in vivo AML models...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29133205/hpma-copolymer-conjugate-with-pirarubicin-in-vitro-and-ex-vivo-stability-and-drug-release-study
#11
Waliul Islam, Jun Fang, Tomas Etrych, Petr Chytil, Karel Ulbrich, Akihiro Sakoguchi, Katsuki Kusakabe, Hiroshi Maeda
We have developed a tumor environment-responsive polymeric anticancer prodrug containing pirarubicin (THP) conjugated to N-(2-hydroxypropyl) methacrylamide copolymer (PHPMA), [P-THP], through a spacer containing pH-sensitive hydrazone bond, that showed remarkable therapeutic effect against various tumor models and in a human pilot study. Toward clinical development, here we report THP release profile from its HPMA copolymer conjugate, the conjugate stability, protein and cell-binding and solubility of P-THP...
November 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29132812/the-antitumor-effect-of-folic-acid-conjugated-auricularia-auricular-polysaccharide-cisplatin-complex-on-cervical-carcinoma-cells-in-nude-mice
#12
Junqiang Qiu, Hua Zhang, Zhenyu Wang, Didi Liu, Shumin Liu, Wei Han, Joe M Regenstein, Lin Geng
A tumor-targeted, folic acid (FA) conjugated-Auricularia auricular polysaccharide (AAP) -cis-diaminedichloroplatinum (CDDP) complex (FA-AAP-CDDP) was used for cervical carcinoma chemotherapy. The drug delivery system was able to enhance the antitumor potency of CDDP, and to reduce the toxic side effects of CDDP. The kidney of mice treated by FA-AAP-CDDP complex had higher superoxide dismutase, catalase, and glutathione peroxidase activities, and lower malondialdehyde. FA-AAP-CDDP complex could induce more interleukin-2, interleukin-4, and interferon-γ in mice...
November 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29132238/nanomicelle-drug-with-acid-triggered-doxorubicin-release-and-enhanced-cellular-uptake-ability-based-on-mpeg-graft-poly-n-2-aminoethyl-l-aspartamide-hexahydrophthalic-acid-copolymers
#13
Li Cao, Yi Xiao, Wei Lu, Shiyuan Liu, Lin Gan, Jiahui Yu, Jin Huang
In order to achieve the passive tumor targeting and acid-triggered drugs release in lysosomes, optimized delivery system for doxorubicin based on pH-sensitive complex nanomicelles with suitable particle size was developed in this research. Particularly, poly(L-succinimide) was thoroughly ring-opened by ethylenediamine to give the poly(N-(2-aminoethyl)-L-aspartamide). Then, graft copolymer mPEG-graft-poly(N-(2-aminoethyl)-L-aspartamide)-hexahydrophthalic acid (mPEG-g-P(ae-Asp)-Hap) was synthesized by grafting mPEG-2000 and hexahydrophthalic anhydride onto poly(N-(2-aminoethyl)-L-aspartamide)...
January 1, 2017: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/29130625/comparative-evaluation-of-68-ga-labeled-nodaga-dotaga-and-hbed-cc-conjugated-cngr-peptide-chelates-as-tumor-targeted-molecular-imaging-probes
#14
Drishty Satpati, Rohit Sharma, Haladhar Dev Sarma, Ashutosh Dash
The biological behavior of (68) Ga-based radiopharmaceuticals can be significantly affected by the chelators' attributes (size, charge, lipophilicity). Thus this study aimed at examining the influence of three different chelators, DOTAGA, NODAGA and HBED-CC on the distribution pattern of (68) Ga-labeled NGR peptides targeting CD13 receptors. (68) Ga-DOTAGA-c(NGR), (68) Ga-NODAGA-c(NGR) and (68) Ga-HBED-CC-c(NGR) were observed to be hydrophilic with respective log P values being -3.5±0.2, -3.3±0.08 and -2...
November 11, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29129804/recent-advances-in-galactose-engineered-nanocarriers-for-the-site-specific-delivery-of-sirna-and-anticancer-drugs
#15
REVIEW
Ashay Jain, Atul Jain, Prahlad Parajuli, Vijay Mishra, Gargi Ghoshal, Bhupinder Singh, Uma Shankar Shivhare, Om Prakash Katare, Prashant Kesharwani
Galactosylated nanocarriers have recently emerged as viable and versatile tools to deliver drugs at an optimal rate specifically to their target tissues or cells, thus maximizing their therapeutic benefits while circumventing off-target effects. The abundance of lectin receptors on cell surfaces makes the galactosylated carriers suitable for the targeted delivery of bioactives. Additionally, tethering of galactose (GAL) to various carriers, including micelles, liposomes, and nanoparticles (NPs), might also be appropriate for drug delivery...
November 10, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/29129789/dual-ph-responsive-multifunctional-nanoparticles-for-targeted-treatment-of-breast-cancer-by-combining-immunotherapy-and-chemotherapy
#16
Yuanyuan Liu, Linan Qiao, Sipei Zhang, Guoyun Wan, Bowei Chen, Ping Zhou, Ning Zhang, Yinsong Wang
In the present study, a dual pH-responsive multifunctional nanoparticle system was designed for combining immunotherapy and chemotherapy to treat breast cancer through targeting immune cells and cancer cells. A proven anti-tumor immune regulator, R848, was encapsulated with poly(L-histidine) (PHIS) to form PHIS/R848 nanocores. Doxorubicin (DOX) was conjugated to hyaluronic acid (HA) through an acid-cleavable hydrazone bond linkage to synthesize polymeric prodrug HA-DOX, which was subsequently coated outside PHIS/R848 nanocores to form HA-DOX/PHIS/R848 nanoparticles...
November 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29129050/metal-free-cycloaddition-chemistry-driven-pretargeted-radioimmunotherapy-using-%C3%AE-particle-radiation
#17
Manan Shah, Xiuli Zhang, Raffaella Rossin, Marc S Robillard, Darrell Fisher, Tyler Bueltmann, Freek J M Hoeben, Thomas Quinn
The pretargeted radioimmunotherapy approach (PRIT) decouples the administration of tumor targeting monoclonal antibodies (mAb) from that of the radiolabeled ligand. This multi-step strategy allows delivery of high doses of radiation to tumor cells while minimizing non-specific normal tissue irradiation. In this study, we evaluated the potential of pretargeted α-particle radioimmunotherapy based on inverse electron demand Diels-Alder reaction (IEDAA) between trans-cyclooctene (TCO) and tetrazine (Tz). Two tetrazine based chelators, DOTA-Tz and TCMC-Tz, were synthesized and compared for their radiolabeling efficiency with 212Pb, radiochemical stability and in-vivo pharmacokinetics...
November 12, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29128847/versatile-hyaluronic-acid-modified-aq4n-cu-ii-gossypol-infinite-coordination-polymer-nanoparticles-multiple-tumor-targeting-highly-efficient-synergistic-chemotherapy-and-real-time-self-monitoring
#18
Shihong Shen, Youshen Wu, Ke Li, Ya Wang, Jimin Wu, Yun Zeng, Daocheng Wu
A novel strategy for the preparation of infinite coordination polymer nanoparticles (ICPs) based nanomedicines was developed, with which hyaluronic acid modified AQ4N-Cu(II)-gossypol nanoparticles (HA@AQ4N-Cu(II)-gossypol NPs) were obtained. This is a highly efficient nanomedicine, in which gossypol serves as a chemotherapeutic agent and a self-carrier material; Cu(II) serves as the connecting point and anti-tumor enhancer; AQ4N not only serves as a chemotherapeutic agent and self-carrier material, but also as the self-monitor based on its inherent fluorescence...
November 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/29128832/delivery-of-paclitaxel-using-nanoparticles-composed-of-poly-ethylene-oxide-b-poly-butylene-oxide-peo-pbo
#19
Lijiang Wang, Ju Yao, Xiaomin Zhang, Yingxin Zhang, Chang Xu, Robert J Lee, Gary Yu, Bo Yu, Lesheng Teng
An amphiphilic block copolymer poly(ethylene oxide)-b-poly(butylene oxide) (PEO-PBO) was evaluated as a carrier for therapeutic delivery of paclitaxel (PTX). PEO-PBO and PTX form nanoparticles (NPs) by self-assembly upon hydration. The size of these NPs was about 92.71nm and the zeta potential was -5.06mV, which met the requirements for passive tumor targeting through the enhanced permeability and retention effect. Compared with a commonly used block copolymer poly(ethylene glycol)-b-poly-D,L-(lactic acid) (PEG-PDLLA), PEO-PBO forms nanoparticles with superior pharmacokinetic, biodistribution, and tumor inhibitory properties...
November 7, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29127457/the-promise-and-challenges-of-exploiting-the-proton-coupled-folate-transporter-for-selective-therapeutic-targeting-of-cancer
#20
REVIEW
Larry H Matherly, Zhanjun Hou, Aleem Gangjee
This review considers the "promise" of exploiting the proton-coupled folate transporter (PCFT) for selective therapeutic targeting of cancer. PCFT was discovered in 2006 and was identified as the principal folate transporter involved in the intestinal absorption of dietary folates. The recognition that PCFT was highly expressed in many tumors stimulated substantial interest in using PCFT for cytotoxic drug targeting, taking advantage of its high level transport activity under the acidic pH conditions that characterize many tumors...
November 10, 2017: Cancer Chemotherapy and Pharmacology
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