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https://www.readbyqxmd.com/read/28771722/co-administration-of-a-tumor-penetrating-peptide-improves-the-therapeutic-efficacy-of-paclitaxel-in-a-novel-air-grown-lung-cancer-3d-spheroid-model
#1
Sweta K Gupta, Elisa A Torrico Guzmán, Samantha A Meenach
Three-dimensional (3D) cell culture platforms are increasingly being used in cancer research and drug development since they mimic avascular tumors in vitro. In the present study, we focused on the development of a novel air-grown multicellular spheroid (MCS) model to mimic in vivo tumors for understanding lung cancer biology and improvement in the evaluation of aerosol anticancer therapeutics. 3D MCS were formed using A549 lung adenocarcinoma cells, comprising cellular heterogeneity with respect to different proliferative and metabolic gradients...
August 2, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28753017/acidity-triggered-ligand-presenting-nanoparticles-to-overcome-sequential-drug-delivery-barriers-to-tumors
#2
Tingting Wang, Dangge Wang, Jianping Liu, Bing Feng, Fangyuan Zhou, Hanwu Zhang, Lei Zhou, Qi Yin, Zhiwen Zhang, Zhonglian Cao, Haijun Yu, Yaping Li
The success of cancer chemotherapy is impeded by poor drug delivery efficiency due to the existence of a series of pathophysiological barriers in the tumor. In this study, we reported a tumor acidity-triggered ligand-presenting (ATLP) nanoparticle for cancer therapy. The ATLP nanoparticles were composed of an acid-responsive diblock copolymer as a sheddable matrix and an iRGD-modified polymeric prodrug of doxorubicin (iPDOX) as an amphiphilic core. A PEG corona of the polymer matrix protected the iRGD ligand from serum degradation and nonspecific interactions with the normal tissues while circulating in the blood...
August 1, 2017: Nano Letters
https://www.readbyqxmd.com/read/28745123/irgd-functionalized-pegylated-nanoparticles-for-enhanced-colon-tumor-accumulation-and-targeted-drug-delivery
#3
Lijun Ma, Qiubing Chen, Panpan Ma, Moon Kwon Han, Zhigang Xu, Yuejun Kang, Bo Xiao, Didier Merlin
AIM: To enhance the tumor accumulation and targeted drug delivery for colon cancer therapy, iRGD peptide was introduced to the surface of PEGylated camptothecin-loaded nanoparticles (NPs). METHODS: Cellular uptake, targeting specificity, biodistribution and antitumor capacity were evaluated. RESULTS: The functionalization of iRGD facilitated tumor accumulation and cellular uptake of NPs by Colon-26 cells. Furthermore, the resultant iRGD-PEG-NPs remarkably improved the therapeutic efficacy of camptothecin in vitro and in vivo by inducing a higher degree of tumor cell apoptosis compared with PEG-NPs...
August 2017: Nanomedicine
https://www.readbyqxmd.com/read/28738522/combination-of-nrp1-mediated-irgd-with-5-fluorouracil-suppresses-proliferation-migration-and-invasion-of-gastric-cancer-cells
#4
Li Zhang, Yanfeng Xing, Qi Gao, Xuejun Sun, Di Zhang, Gang Cao
Gastric cancer is one of the most of common cancers in the world. 5-Fluorouracil (5-FU) has been identified as one of the standard first-line chemotherapy drugs for locally advanced or metastatic gastric cancer. However, poor tumor penetration, bad selectivity and toxic side effects are the major limitations for the application of chemotherapy drugs in anticancer therapy. Recently, plenty of studies demonstrate that the novel tumor-homing peptide iRGD could promote the tumor-penetrating capability of chemotherapy drugs in multiple cancers, and neuropilin-1 (NRP1) protein is the critical mediator for iRGD...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28681981/ros-responsive-polyprodrug-nanoparticles-for-triggered-drug-delivery-and-effective-cancer-therapy
#5
Xiaoding Xu, Phei Er Saw, Wei Tao, Yujing Li, Xiaoyuan Ji, Sushant Bhasin, Yanlan Liu, Dana Ayyash, Jonathan Rasmussen, Marc Huo, Jinjun Shi, Omid C Farokhzad
The application of nanoparticles (NPs) to drug delivery has led to the development of novel nanotherapeutics for the treatment of various diseases including cancer. However, clinical use of NP-mediated drug delivery has not always translated into improved survival of cancer patients, in part due to the suboptimal properties of NP platforms, such as premature drug leakage during preparation, storage, or blood circulation, lack of active targeting to tumor tissue and cells, and poor tissue penetration. Herein, an innovative reactive oxygen species (ROS)-responsive polyprodrug is reported that can self-assemble into stable NPs with high drug loading...
July 6, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28666009/delivery-of-gene-targeting-sirnas-to-breast-cancer-cells-using-a-multifunctional-peptide-complex-that-promotes-both-targeted-delivery-and-endosomal-release
#6
Jeffrey D Bjorge, Andy Pang, Donald J Fujita
RNA interference has been used to dissect the importance of individual gene products in various human disease processes, including cancer. Small-interfering RNA, or siRNA, is one of the tools utilized in this regard, but specially-designed delivery agents are required to allow the siRNA to gain optimal access to the cell interior. Our laboratory has utilized two different siRNA-binding delivery peptides containing a polyarginine core, and modified by myristoylation and targeting motifs (iRGD or Lyp-1). A third peptide was designed to assist with endosomal release...
2017: PloS One
https://www.readbyqxmd.com/read/28631963/tumor-penetrating-peptide-integrated-thermally-sensitive-liposomal-doxorubicin-enhances-efficacy-of-radiofrequency-ablation-in-liver-tumors
#7
Fei Yan, Song Wang, Wei Yang, S Nahum Goldberg, Hao Wu, Wan-Lu Duan, Zhi-Ting Deng, Hai-Bo Han, Hai-Rong Zheng
Purpose To investigate the role of a tumor-penetrating peptide (internalizing CRGDRGPDC [iRGD])-integrated thermally sensitive liposomal (TSL) doxorubicin (DOX) in combination with radiofrequency (RF) ablation of liver tumors in an animal model. Materials and Methods Approval from the institutional animal care and use committee was obtained. Characterization of iRGD-TSL-DOX was performed in vitro. Next, H22 liver adenocarcinomas were implanted in 138 mice in vivo. The DOX accumulation and cell apoptosis of iRGD-TSL-DOX and TSL-DOX with or without RF were evaluated (n = 5) at different time points after treatment with quantitative analysis or pathologic staining...
June 19, 2017: Radiology
https://www.readbyqxmd.com/read/28615942/irgd-modified-lipid-polymer-hybrid-nanoparticles-loaded-with-isoliquiritigenin-to-enhance-anti-breast-cancer-effect-and-tumor-targeting-ability
#8
Fei Gao, Jinming Zhang, Chaomei Fu, Xiaoming Xie, Fu Peng, Jieshu You, Hailin Tang, Zhiyu Wang, Peng Li, Jianping Chen
Isoliquiritigenin (ISL), a natural anti-breast cancer dietary compound, has poor delivery characteristics and low bioavailability. In order to promote the therapeutic outcome of ISL, a tumor-targeting lipid-polymer hybrid nanoparticle (NP) system modified by tumor-homing iRGD peptides has been developed. The hybrid NPs were prepared by a modified single-step nanoprecipitation method to encapsulate ISL. iRGD peptides were anchored on the surface by a postinsertion method (ISL-iRGD NPs). The stable lipid-polymer structure of ISL-iRGD NPs, with high encapsulation and loading efficiency, was confirmed...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28595131/a-precision-guided-mwnt-mediated-reawakening-the-sunk-synergy-in-ras-for-anti-angiogenesis-lung-cancer-therapy
#9
Yujie Su, Yahui Hu, Yu Wang, Xiangting Xu, Yang Yuan, Yunman Li, Zeyuan Wang, Kerong Chen, Fangrong Zhang, Xuefang Ding, Min Li, Jianping Zhou, Yuan Liu, Wei Wang
Multi-walled carbon nanotube (MWNT) with its versatility has exhibited tremendous superiority in drug delivery. Despite plenty of researches on MWNT based delivery systems, precision-guided assistances to maximize their profitable properties are still lacking in substantive progress. We developed here a dual-targeting and co-delivery system based on MWNT for antiangiogenesis therapy in lung cancer which aimed at renin-angiotensin system (RAS) dysregulation by synergistically conducting angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) pathway...
September 2017: Biomaterials
https://www.readbyqxmd.com/read/28544965/nrgd-modified-lycobetaine-and-octreotide-combination-delivery-system-to-overcome-multiple-barriers-and-enhance-anti-glioma-efficacy
#10
Tijia Chen, Xu Song, Ting Gong, Yao Fu, Liuqing Yang, Zhirong Zhang, Tao Gong
For glioma as one of the most common and lethal primary brain tumors, the presence of BBB, BBTB, vasculogenic mimicry (VM) channels and tumor-associated macrophages (TAMs) are key biological barriers. Here, a novel drug delivery system which could efficiently deliver drugs to glioma by overcoming multi-barriers and increase antitumor efficacy through multi-therapeutic mechanisms was well developed. In this study, a multi-target peptide nRGD was used to transport across the BBB, mediate tumor penetration and target TAMs...
May 15, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28481085/harnessing-phosphato-platinum-bonding-induced-supramolecular-assembly-for-systemic-cisplatin-delivery
#11
Yingqin Hou, Yaoyi Wang, Ruijue Wang, Weier Bao, Xiaobo Xi, Yunlong Sun, Shengtao Yang, Wei Wei, Hua Lu
To improve the therapeutic index of cisplatin (CDDP), we present here a new paradigm of drug-induced self-assembly by harnessing phosphato-platinum complexation. Specifically, we show that a phosphato-platinum cross-linked micelle (PpY/Pt) can be generated by using a block copolymer methoxy-poly(ethylene glycol)-block-poly(l-phosphotyrosine) (mPEG-b-PpY). Coating of PpY/Pt with a R9-iRGD peptide by simple mixing affords a targeting micelle with near neutral-charged surface (iPpY/Pt). The micelles feature in well-controlled sizes below 50 nm and high stability under physiological conditions, and can withstand various environmental stresses...
May 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28470171/co-delivery-of-paclitaxel-and-tetrandrine-via-irgd-peptide-conjugated-lipid-polymer-hybrid-nanoparticles-overcome-multidrug-resistance-in-cancer-cells
#12
Jinming Zhang, Lu Wang, Hon Fai Chan, Wei Xie, Sheng Chen, Chengwei He, Yitao Wang, Meiwan Chen
One of the promising strategies to overcome tumor multidrug resistance (MDR) is to deliver anticancer drug along with P-glycoprotein (P-gp) inhibitor simultaneously. To enhance the cancer cellular internalization and implement the controlled drug release, herein an iRGD peptide-modified lipid-polymer hybrid nanosystem (LPN) was fabricated to coload paclitaxel (PTX) and tetrandrine (TET) at a precise combination ratio. In this co-delivery system, PTX was covalently conjugated to poly (D,L-lactide-co-glycolide) polymeric core by redox-sensitive disulfide bond, while TET was physically capsulated spontaneously for the aim to suppress P-gp in advance by the earlier released TET in cancer cells...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28414298/access-granted-irgd-helps-silicasome-encased-drugs-breach-the-tumor-barrier
#13
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...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28414297/tumor-penetrating-peptide-enhances-transcytosis-of-silicasome-based-chemotherapy-for-pancreatic-cancer
#14
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...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28377488/u1-adaptors-suppress-the-kras-myc-oncogenic-axis-in-human-pancreatic-cancer-xenografts
#15
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)...
August 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28373646/strail-irgd-is-a-promising-therapeutic-agent-for-gastric-cancer-treatment
#16
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
#17
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
#18
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
#19
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
#20
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
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