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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
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...
February 10, 2017: Oncology Reports
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
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
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
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
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
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
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
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
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
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
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
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
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
Jianguo Wang, Hangxiang Wang, Jie Li, Zhikun Liu, Haiyang Xie, Xuyong Wei, Di Lu, Runzhou Zhuang, Xiao Xu, Shusen Zheng
Molecularly targeted agents that are designed to target specific lesions have been proven effective as clinical cancer therapies; however, most currently available therapeutic agents are poorly water-soluble and require oral administration, thereby resulting in low bioavailability and a high risk of side effects due to dose intensification. The rational engineering of systemically injectable medicines that encapsulate such therapeutic payloads may revolutionize anticancer therapies and remains an under-explored area of drug development...
August 3, 2016: ACS Applied Materials & Interfaces
Hong-Jun Cho, Sung-Jin Lee, Sung-Jun Park, Chang H Paik, Sang-Myung Lee, Sehoon Kim, Yoon-Sik Lee
A disulfide-bridged cyclic RGD peptide, named iRGD (internalizing RGD, c(CRGDK/RGPD/EC)), is known to facilitate tumor targeting as well as tissue penetration. After the RGD motif-induced targeting on αv integrins expressed near tumor tissue, iRGD encounters proteolytic cleavage to expose the CendR motif that promotes penetration into cancer cells via the interaction with neuropilin-1. Based on these proteolytic cleavage and internalization mechanism, we designed an iRGD-based monolithic imaging probe that integrates multiple functions (cancer-specific targeting, internalization and fluorescence activation) within a small peptide framework...
September 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Xinyu Bian, Puyuan Wu, Huizi Sha, Hanqing Qian, Qing Wang, Lei Cheng, Yang Yang, Mi Yang, Baorui Liu
In this study, we report a novel kind of targeting with paclitaxel (PTX)-loaded silk fibroin nanoparticles conjugated with iRGD-EGFR nanobody recombinant protein (anti-EGFR-iRGD). The new nanoparticles (called A-PTX-SF-NPs) were prepared using the carbodiimide-mediated coupling procedure and their characteristics were evaluated. The cellular cytotoxicity and cellular uptake of A-PTX-SF-NPs were also investigated. The results in vivo suggested that NPs conjugated with the recombinant protein exhibited more targeting and anti-neoplastic property in cells with high EGFR expression...
2016: OncoTargets and Therapy
Zhu Jin, Yaqi Lv, Hui Cao, Jing Yao, Jianping Zhou, Wei He, Lifang Yin
Rapid blood clearance and premature burst release are inherent drawbacks of conventional nanoparticles, resulting in poor tumor selectivity. iRGD peptide is widely recognized as an efficient cell membrane penetration peptide homing to αVβ3 integrins. Herein, core-shell nanocapsules (NCs) and iRGD-modified NCs (iRGD-NCs) with high drug payload for paclitaxel (PTX) were prepared to enhance the antitumor activities of chemotherapy agents with poor water solubility. Improved in vitro and in vivo tumor targeting and penetration were observed with NCs and iRGD-NCs; the latter exhibited better antitumor activity because iRGD enhanced the accumulation and penetration of NCs in tumors...
2016: Scientific Reports
Bárbara Herranz-Blanco, Mohammad-Ali Shahbazi, Alexandra R Correia, Vimalkumar Balasubramanian, Tomáš Kohout, Jouni Hirvonen, Hélder A Santos
Theranostic nanoparticles are emerging as potent tools for noninvasive diagnosis, treatment, and monitoring of solid tumors. Herein, an advanced targeted and multistimuli responsive theranostic platform is presented for the intracellular triggered delivery of doxorubicin. The system consists of a polymeric-drug conjugate solid nanoparticle containing encapsulated superparamagnetic iron oxide nanoparticles (IO@PNP) and decorated with a tumor homing peptide, iRGD. The production of this nanosystem is based on a pH-switch nanoprecipitation method in organic-free solvents, making it ideal for biomedical applications...
August 2016: Advanced Healthcare Materials
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