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iRGD

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https://www.readbyqxmd.com/read/28414298/access-granted-irgd-helps-silicasome-encased-drugs-breach-the-tumor-barrier
#1
Erkki Ruoslahti
In this issue of the JCI, Liu et al. use irinotecan-loaded nanoparticles to treat pancreatic adenocarcinomas in mice. Encapsulating drugs into nanoparticles has distinct advantages: it can improve the pharmacokinetics of the drug, enhance efficacy, and reduce unwanted side effects. A drawback is that the large size of nanoparticles restricts their access to the tumor interior. Liu and colleagues show that the cyclic tumor-penetrating peptide iRGD, reported to be capable of enhancing tumor penetration by drugs, can overcome this limitation to a substantial degree when administered together with the nanoparticles...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28414297/tumor-penetrating-peptide-enhances-transcytosis-of-silicasome-based-chemotherapy-for-pancreatic-cancer
#2
Xiangsheng Liu, Paulina Lin, Ian Perrett, Joshua Lin, Yu-Pei Liao, Chong Hyun Chang, Jinhong Jiang, Nanping Wu, Timothy Donahue, Zev Wainberg, Andre E Nel, Huan Meng
Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some improvement in overall survival has been achieved with the introduction of nanocarriers that deliver irinotecan or paclitaxel. Although it is generally assumed that nanocarriers rely principally on abnormal leaky vasculature for tumor access, a transcytosis transport pathway that is regulated by neuropilin-1 (NRP-1) has recently been reported. NRP-1-mediated transport can be triggered by the cyclic tumor-penetrating peptide iRGD...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28377488/u1-adaptors-suppress-the-kras-myc-oncogenic-axis-in-human-pancreatic-cancer-xenografts
#3
Ashley T Tsang, Crissy Dudgeon, Lan Yi, Xin Yu, Rafal Goraczniak, Kristen Donohue, Samuel Kogan, Mark A Brenneman, Eric S Ho, Samuel I Gunderson, Darren R Carpizo
Targeting KRAS and MYC has been a tremendous challenge in cancer drug development. Genetic studies in mouse models have validated the efficacy of silencing expression of both KRAS and MYC in mutant KRAS driven tumors. We investigated the therapeutic potential of a new oligonucleotide-mediated gene silencing technology (U1 Adaptor) targeting KRAS and MYC in pancreatic cancer. Nanoparticles in complex with anti-KRAS U1 Adaptors (U1-KRAS) showed remarkable inhibition of KRAS in different human pancreatic cancer cell lines in vitro and in vivo As a nanoparticle-free approach is far easier to develop into a drug, we refined the formulation of U1 Adaptors by conjugating them to tumor targeting peptides (iRGD and cRGD)...
April 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28373646/strail-irgd-is-a-promising-therapeutic-agent-for-gastric-cancer-treatment
#4
Ying Huang, Xihan Li, Huizi Sha, Lianru Zhang, Xinyu Bian, Xiao Han, Baorui Liu
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells and augments chemotherapeutics in vivo. Here, we developed sTRAIL-iRGD, a recombinant protein consisting of sTRAIL fused to CRGDKGPDC, a C-terminal end binding peptide with an integrin-binding arginine-glycine-aspartic acid (iRGD) motif. CRGDKGPDC is a tumor-homing peptide with high penetration into tumor tissue and cells. We found that sTRAIL-iRGD internalized into cultured gastric cancer tumor cells and localized to both the tumor mass in vivo and three-dimensional multicellular spheroids in vitro...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28358432/irgd-as-a-tumor%C3%A2-penetrating-peptide-for-cancer-therapy-review
#5
Hong Yin, Jie Yang, Qing Zhang, Jie Yang, Haiyu Wang, Jinjing Xu, Junnian Zheng
As a tumor-targeting and ‑penetrating peptide, iRGD binds to αv integrins and neuropilin‑1 receptors, which are expressed at high levels on tumor cells and the surfaces of vasculature. Subsequently, iRGD penetrates deep into the tumor parenchyma with antitumor drugs, imaging agents, immune modulators and biological products. These substances are either chemically linked to the peptide or co‑injected with the peptide. The iRGD peptide can be readily synthesized, exhibits significantly improved penetration, compared with traditional peptides, and can effectively inhibit tumor metastasis...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28260884/topical-ocular-delivery-to-laser-induced-choroidal-neovascularization-by-dual-internalizing-rgd-and-tat-peptide-modified-nanoparticles
#6
Yongchao Chu, Ning Chen, Huajun Yu, Hongjie Mu, Bin He, Hongchen Hua, Aiping Wang, Kaoxiang Sun
A nanoparticle (NP) was developed to target choroidal neovascularization (CNV) via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC) and transactivated transcription (TAT) (RKKRRQRRRC) peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. (1)H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol)- poly(lactic-co-glycolic acid)...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28260064/tumor-penetrating-peptide-fused-to-a-pro-apoptotic-peptide-facilitates-effective-gastric-cancer-therapy
#7
Ying Huang, Xihan Li, Huizi Sha, Lianru Zhang, Xinyu Bian, Xiao Han, Baorui Liu
KLA (sequence, KLAKLAKKLAKLAK) is a peptide which leads to programmed cell death by disrupting the mitochondrial membrane. However, low penetration in tumors greatly limits its application and efficacy. To develop a KLA-based cancer therapy, KLA-iRGD, a recombinant protein was constructed. It consists of the KLA peptide and iRGD (CRGDKGPDC), a tumor-homing peptide with high penetration into tumor tissue and cells. The conjugated KLA exhibits pro-apoptotic activity to prevent the growth of a tumor once it is inside the cell...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28165223/tumor-penetrating-nanoparticles-for-enhanced-anticancer-activity-of-combined-photodynamic-and-hypoxia-activated-therapy
#8
Yazhe Wang, Ying Xie, Jing Li, Zheng-Hong Peng, Yuri Sheinin, Jianping Zhou, David Oupický
Poor tumor penetration is a major challenge for the use of nanoparticles in anticancer therapy. Moreover, the inability to reach hypoxic tumor cells that are distant from blood vessels results in inadequate exposure to antitumor therapeutics and contributes to development of chemoresistance and increased metastasis. In the present study, we developed iRGD-modified nanoparticles for simultaneous tumor delivery of a photosensitizer indocyanine green (ICG) and hypoxia-activated prodrug tirapazamine (TPZ). The iRGD-modified nanoparticles loaded with ICG and TPZ showed significantly improved penetration in both 3D tumor spheroids in vitro and orthotopic breast tumors in vivo...
February 28, 2017: ACS Nano
https://www.readbyqxmd.com/read/28100395/replication-study-coadministration-of-a-tumor-penetrating-peptide-enhances-the-efficacy-of-cancer-drugs
#9
Christine Mantis, Irawati Kandela, Fraser Aird
In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Kandela et al., 2015) that described how we intended to replicate selected experiments from the paper "Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs" (Sugahara et al., 2010). Here we report the results of those experiments. We found that coadministration with iRGD peptide did not have an impact on permeability of the chemotherapeutic agent doxorubicin (DOX) in a xenograft model of prostate cancer, whereas the original study reported that it increased the penetrance of this cancer drug (Figure 2B; Sugahara et al...
January 19, 2017: ELife
https://www.readbyqxmd.com/read/28009503/coadministration-of-oligomeric-hyaluronic-acid-modified-liposomes-with-tumor-penetrating-peptide-irgd-enhances-the-antitumor-efficacy-of-doxorubicin-against-melanoma
#10
Caifeng Deng, Quan Zhang, Yao Fu, Xun Sun, Tao Gong, Zhirong Zhang
A safe and efficient tumor-targeting strategy based on oligomeric hyaluronic acid (HA) modification and coadministration of tumor-penetrating peptide-iRGD was successfully developed. In this study, common liposomes (cLip) were modified by oligomeric HA to obtain HA-Lip. After injection into rats, HA-Lip showed good stealth in the bloodstream and lower liver distribution compared with cLip. Moreover, our HA-Lip could be internalized into B16F10 cells (CD44-overexpressing tumor cells) through HA-CD44 interaction...
January 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27984104/hyperthermia-triggered-drug-delivery-from-irgd-modified-temperature-sensitive-liposomes-enhances-the-anti-tumor-efficacy-using-high-intensity-focused-ultrasound
#11
Zhiting Deng, Yang Xiao, Min Pan, Fei Li, Wanlu Duan, Long Meng, Xin Liu, Fei Yan, Hairong Zheng
An important limitation to successful cancer treatment with chemotherapeutics is the inability to achieve therapeutically effective drug concentrations while avoiding healthy tissue damage. In this work, a new tumor-targeting peptide iRGD (CCRGDKGPDC) was used to modify drug-loaded low temperature-sensitive liposomes (iRGD-LTSL-DOX) to explore the anti-tumor effects in combination with high intensity focused ultrasound (HIFU) in vitro and in vivo. iRGD-LTSL-DOX can specifically target to ανβ3-positive cells and locally release the encapsulated doxorubicin (DOX) in a hyperthermia-triggered manner...
December 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27936775/inducing-optimal-antitumor-immune-response-through-coadministering-irgd-with-pirarubicin-loaded-nanostructured-lipid-carriers-for-breast-cancer-therapy
#12
Caifeng Deng, Mengdi Jia, Guangfei Wei, Tiantian Tan, Yao Fu, Huile Gao, Xun Sun, Quan Zhang, Tao Gong, Zhirong Zhang
Chemotherapeutic agents trigger antitumor immune response through inducing immunogenic tumor cell death. However, severe toxicity to immune system and insufficient immunogenic cell death hinder chemotherapy from arousing efficient antitumor immunity in vivo. In this study, the cytotoxic drug, pirarubicin (THP), was entrapped into nanostructured lipid carriers (NLC); THP-NLC significantly reduced the toxicity of THP to immune system and improved immune status of breast cancer bearing mice. When THP-NLC was coinjected with iRGD (a tumor-penetrating peptide), drug accumulation in tumors was greatly elevated, which led to significant control of tumor growth and increase of immunogenic tumor cell death...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27899989/tumor-penetration-and-antitumor-efficacy-of-cetuximab-are-enhanced-by-co-administered-irgd-in-a-murine-model-of-human-nsclc
#13
Yang Zhang, Jie Yang, Manhua Ding, Liantao Li, Zheng Lu, Qing Zhang, Junnian Zheng
Lung cancer is the leading cause of cancer-associated mortality, worldwide. For this reason, novel therapies are required for the treatment of this devastating disease. Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR), which is overexpressed in a variety of solid tumors, including non-small cell lung cancer (NSCLC). The therapeutic efficacy of cetuximab for NSCLC is limited to use as a monotherapy or in combination with chemotherapy. The objective of the present study was to develop a novel strategy to enhance the therapeutic efficacy of cetuximab for NSCLC by a co-administration with the tumor-penetrating internalizing RGD peptide (iRGD)...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27712073/highly-stable-fluorinated-nanocarriers-with-irgd-for-overcoming-the-stability-dilemma-and-enhancing-tumor-penetration-in-an-orthotopic-breast-cancer
#14
Shengnan Ma, Jie Zhou, Yuxin Zhang, Yiyan He, Qian Jiang, Dong Yue, Xianghui Xu, Zhongwei Gu
The stability dilemma and limited tumor penetration of nanocarriers in cancer chemotherapy remain two predominant challenges for their successful clinical translation. Herein, the pH-sensitive fluorocarbon functionalized nanocarriers (SFNs) with a tumor homing and penetrating peptide iRGD are reported to overcome the stability dilemma and enhance tumor accumulation and penetration in an orthotopic breast cancer. The highly stable SFNs with a low critical association concentration provide a safe and spacious harbor for hydrophobic drugs...
October 7, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27646474/irgd-mediated-core-shell-nanoparticles-loading-carmustine-and-o-6-benzylguanine-for-glioma-therapy
#15
Chang Liu, Sen Yao, Xuqian Li, Feng Wang, Yanyan Jiang
iRGD (internalizing RGD) with high affinity to αν integrins was reported to enhance tumor penetrability by binding to neuropilin-1 (NRP-1). Based on our previous study, chitosan surface-modified poly (lactide-co-glycolides) nanoparticles (PLGA/CS NPs), loaded with carmustine (BCNU) and its sensitizer (O(6)-benzylguanine, BG) showed stronger anti-tumor effect than free drugs. In present study, PLGA/CS NPs (NPs) with core-shell structure were prepared and modified with iRGD or mPEG. F98, C6 or U87 cell lines with different receptors levels were selected for in vitro and in vivo studies...
October 6, 2016: Journal of Drug Targeting
https://www.readbyqxmd.com/read/27619239/development-of-a-multi-target-peptide-for-potentiating-chemotherapy-by-modulating-tumor-microenvironment
#16
Xu Song, Zhuoya Wan, Tijia Chen, Yao Fu, Kejun Jiang, Xiaoli Yi, Huan Ke, Jianxia Dong, Liuqing Yang, Lin Li, Xun Sun, Tao Gong, Zhirong Zhang
Finding effective cures against aggressive malignancy remains a major challenge in cancer chemotherapy. Here, we report a "tadpole"-like peptide by covalently conjugating the alanine-alanine-asparagine "tail" residual to the cyclic tumor homing peptide iRGD (CCRGDKGPDC) to afford nRGD, which significantly enhanced tumoricidal effects of doxorubicin, by either co-administered as a physical mixture or as a targeting ligand covalently conjugated to the liposomal carrier. Given twice at an equivalent dose of 5 mg/kg, doxorubicin loaded liposomes modified with nRGD (nRGD-Lipo-Dox) showed excellent antitumor efficacy in 4T1 breast cancer mice, of which 44...
November 2016: Biomaterials
https://www.readbyqxmd.com/read/27513518/tumor-specific-peptide-selected-from-a-phage-peptide-library-enhances-antitumor-activity-of-lactaptin
#17
Anna A Nemudraya, Anna A Makartsova, Alexandr S Fomin, Anna A Nushtaeva, Olga A Koval, Vladimir A Richter, Elena V Kuligina
A recombinant analogue of lactaptin (RL2), a new potential anticancer molecule, induces apoptosis in cultured tumor cells. The tumor suppression efficacy of RL2 was shown against mouse hepatoma-1 cells and MDA-MB-231 human breast adenocarcinoma cells. The RL2-based therapeutic drug lactaptin is distributed evenly throughout the organism, which reduces its antitumor efficacy. In the current study, we obtained a genetic construct that allows production of the recombinant fusion protein T3-RL2, consisting of RL2 and T3 peptide (YTYDPWLIFPAN), in E...
2016: PloS One
https://www.readbyqxmd.com/read/27511949/targeted-cancer-therapy-ph-switch-nanoprecipitation-of-polymeric-nanoparticles-for-multimodal-cancer-targeting-and-intracellular-triggered-delivery-of-doxorubicin-adv-healthcare-mater-15-2016
#18
Bárbara Herranz-Blanco, Mohammad-Ali Shahbazi, Alexandra R Correia, Vimalkumar Balasubramanian, Tomáš Kohout, Jouni Hirvonen, Hélder A Santos
Targeted theranostic nanoparticles with dual pH and magnetic responsive properties for intracellular delivery are described by B. Herranz-Blanco, H. A. Santos, and co-workers on page 1904. Using a pH-switch nanoprecipitation method in organic-free solvents, a polymeric-drug conjugate solid nanoparticle containing encapsulated superparamagnetic iron oxide nanoparticles and decorated with a tumor homing peptide, iRGD, are targeted to endothelial and metastatic cancer cells.
August 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27472162/irgd-peptide-conjugation-potentiates-intraperitoneal-tumor-delivery-of-paclitaxel-with-polymersomes
#19
Lorena Simón-Gracia, Hedi Hunt, Pablo Scodeller, Jens Gaitzsch, Venkata Ramana Kotamraju, Kazuki N Sugahara, Olav Tammik, Erkki Ruoslahti, Giuseppe Battaglia, Tambet Teesalu
Polymersomes are versatile nanoscale vesicles that can be used for cytoplasmic delivery of payloads. Recently, we demonstrated that pH-sensitive polymersomes exhibit an intrinsic selectivity towards intraperitoneal tumor lesions. A tumor homing peptide, iRGD, harbors a cryptic C-end Rule (CendR) motif that is responsible for neuropilin-1 (NRP-1) binding and for triggering extravasation and tumor penetration of the peptide. iRGD functionalization increases tumor selectivity and therapeutic efficacy of systemic drug-loaded nanoparticles in many tumor models...
October 2016: Biomaterials
https://www.readbyqxmd.com/read/27386551/tumor-homing-peptides-as-tools-for-targeted-delivery-of-payloads-to-the-placenta
#20
Anna King, Cornelia Ndifon, Sylvia Lui, Kate Widdows, Venkata R Kotamraju, Lilach Agemy, Tambet Teesalu, Jocelyn D Glazier, Francesco Cellesi, Nicola Tirelli, John D Aplin, Erkki Ruoslahti, Lynda K Harris
The availability of therapeutics to treat pregnancy complications is severely lacking mainly because of the risk of causing harm to the fetus. As enhancement of placental growth and function can alleviate maternal symptoms and improve fetal growth in animal models, we have developed a method for targeted delivery of payloads to the placenta. We show that the tumor-homing peptide sequences CGKRK and iRGD bind selectively to the placental surface of humans and mice and do not interfere with normal development...
May 2016: Science Advances
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