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Lise Roth Lilach Agemy V. Ramana Kotamraju Gary Braun Tambet Teesalu Kazuki Sugahara J, Hamzah Erkki Ruoslahti
Published in
Oncogene
We have recently described a class of peptides that improve drug delivery by increasing penetration of drugs into solid tumors. These peptides contain a C-terminal C-end Rule (CendR) sequence motif (R/K)XX(R/K), which is responsible for cell internalization and tissue-penetration activity. Tumor-specific CendR peptides contain both a tumor-homing m...
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J, Wang Y, Liu Tambet Teesalu Kazuki Sugahara Vr, Kotamrajua Jd, Adams Bs, Ferguson Q, Gong Ss, Oh At, Csordas
...
Published in
Proceedings of the National Academy of Sciences
Affinity reagents that bind to specific molecular targets are an essential tool for both diagnostics and targeted therapeutics. There is a particular need for advanced technologies for the generation of reagents that specifically target cell-surface markers, because transmembrane proteins are notoriously difficult to express in recombinant form. We...
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Kazuki Sugahara Tambet Teesalu Priya Karmali V. Ramana Kotamraju Lilach Agemy Dr, Greenwald Erkki Ruoslahti
Published in
Science
Poor penetration of anticancer drugs into tumors can be an important factor limiting their efficacy. We studied mouse tumor models to show that a previously characterized tumor-penetrating peptide, iRGD, increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing coadministered drugs to penetrate into ...
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Hb, Pang Gary Braun Zg, She V. Ramana Kotamraju Kazuki Sugahara Tambet Teesalu Erkki Ruoslahti
Published in
Journal of Controlled Release
The accessibility of extravascular tumor tissue to drugs is critical for therapeutic efficacy. We previously described a tumor-targeting peptide (iRGD) that elicits active transport of drugs and macromolecules (covalently coupled or co-administered) across the vascular wall into tumor tissue. Short peptides (iRGD is a 9-amino acid cyclic peptide) g...
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Kazuki Sugahara Tambet Teesalu Priya Karmali V. Ramana Kotamraju Lilach Agemy Om, Girard D, Hanahan Rf, Mattrey Erkki Ruoslahti
Published in
Cancer Cell International
Poor penetration of drugs into tumors is a major obstacle in tumor treatment. We describe a strategy for peptide-mediated delivery of compounds deep into the tumor parenchyma that uses a tumor-homing peptide, iRGD (CRGDK/RGPD/EC). Intravenously injected compounds coupled to iRGD bound to tumor vessels and spread into the extravascular tumor parench...
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Gary Braun Kazuki Sugahara Om, Yu V. Ramana Kotamraju T, Mölder Am, Lowy Erkki Ruoslahti Tambet Teesalu
Published in
Journal of Controlled Release
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Am, Hamilton S, Aidoudi-Ahmed S, Sharma V. Ramana Kotamraju Pj, Foster Kazuki Sugahara Erkki Ruoslahti Bk, Rutt
Published in
Journal of Molecular Medicine
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Aa, Willmore L, Simón-Gracia K, Toome P, Paiste V. Ramana Kotamraju T, Mölder Kazuki Sugahara Erkki Ruoslahti Gary Braun Tambet Teesalu
...
Published in
Nanoscale
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Renwei Chen Gary Braun X, Luo Kazuki Sugahara Tambet Teesalu Erkki Ruoslahti
Published in
Cancer Research
Bit1 is a proapoptotic mitochondrial protein associated with anoikis. Upon cell detachment, Bit1 is released into the cytoplasm and triggers caspase-independent cell death. Bit1 consists of 179 amino acids; for the C-terminal, two thirds of the molecule functions as a peptidyl-tRNA hydrolase, whereas the N-terminus contains a mitochondrial localiza...
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L, Alberici Lise Roth Kazuki Sugahara Lilach Agemy V. Ramana Kotamraju Tambet Teesalu C, Bordignon C, Traversari Gp, Rizzardi Erkki Ruoslahti
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Published in
Cancer Research
Poor penetration of antitumor drugs into the extravascular tumor tissue is often a major factor limiting the efficacy of cancer treatments. Our group has recently described a strategy to enhance tumor penetration of chemotherapeutic drugs through use of iRGD peptide (CRGDK/RGPDC). This peptide comprises two sequence motifs: RGD, which binds to αvβ3...
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Gary Braun T, Friman Hb, Pang A, Pallaoro T, Hurtado De Mendoza Am, Willmore V. Ramana Kotamraju Ap, Mann Zg, She Kazuki Sugahara
...
Published in
Nature Materials
There is considerable interest in using nanoparticles as labels or to deliver drugs and other bioactive compounds to cells in vitro and in vivo. Fluorescent imaging, commonly used to study internalization and subcellular localization of nanoparticles, does not allow unequivocal distinction between cell surface-bound and internalized particles, as t...
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Tambet Teesalu Kazuki Sugahara Erkki Ruoslahti
Published in
Frontiers in Oncology
Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC), contains the integrin-...
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Kazuki Sugahara P, Scodeller Gary Braun Th, De Mendoza Cm, Yamazaki Md, Kluger J, Kitayama E, Alvarez Sb, Howell Tambet Teesalu
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Published in
Journal of Controlled Release
Peritoneal carcinomatosis is a major source of morbidity and mortality in patients with advanced abdominal neoplasms. Intraperitoneal chemotherapy (IPC) is an area of intense interest given its efficacy in ovarian cancer. However, IPC suffers from poor drug penetration into peritoneal tumors. As such, extensive cytoreductive surgery is required pri...
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Valentina Fogal Kazuki Sugahara Erkki Ruoslahti S, Christian
Published in
Angiogenesis
Nucleolin is specifically transported to the surface of proliferating endothelial cells in vitro and in vivo. In contrast to its well defined functions in the nucleus and cytoplasm, the function of cell surface nucleolin is poorly defined. We have previously identified the nucleolin-binding antibody NCL3 that specifically binds to cell surface nucl...
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Hb, Pang Gary Braun T, Friman P, Aza-Blanc Me, Ruidiaz Kazuki Sugahara Tambet Teesalu Erkki Ruoslahti
Published in
Nature Communications
Neuropilins (NRPs) are trans-membrane receptors involved in axon guidance and vascular development. Many growth factors and other signalling molecules bind to NRPs through a carboxy (C)-terminal, basic sequence motif (C-end Rule or CendR motif). Peptides with this motif (CendR peptides) are taken up into cells by endocytosis. Tumour-homing CendR pe...
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Kazuki Sugahara Gary Braun Th, De Mendoza V. Ramana Kotamraju Rp, French Am, Lowy Tambet Teesalu Erkki Ruoslahti
Published in
Molecular Cancer Therapeutics
Tumor-specific tissue-penetrating peptides deliver drugs into extravascular tumor tissue by increasing tumor vascular permeability through interaction with neuropilin (NRP). Here, we report that a prototypic tumor-penetrating peptide iRGD (amino acid sequence: CRGDKGPDC) potently inhibits spontaneous metastasis in mice. The antimetastatic effect wa...
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Lilach Agemy Kazuki Sugahara V. Ramana Kotamraju K, Gujraty Om, Girard Y, Kono Rf, Mattrey Ji Ho Park Mj, Sailor Ai, Jimenez
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Published in
Blood
The tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) specifically homes to tumors by binding to fibrin and fibrin-associated clotted plasma proteins in tumor vessels. Previous results show that CREKA-coated superparamagnetic iron oxide particles can cause additional clotting in tumor vessels, which creates more binding sites for the peptide. W...
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D, Sánchez-Martín J, Martínez-Torrecuadrada Tambet Teesalu Kazuki Sugahara A, Alvarez-Cienfuegos P, Ximénez-Embún R, Fernández-Periáñez Mt, Martín I, Molina-Privado I, Ruppen-Cañás
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Published in
Proceedings of the National Academy of Sciences
Antibody cancer therapies rely on systemically accessible targets and suitable antibodies that exert a functional activity or deliver a payload to the tumor site. Here, we present proof-of-principle of in vivo selection of human antibodies in tumor-bearing mice that identified a tumor-specific antibody able to deliver a payload and unveils the targ...
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Tambet Teesalu Kazuki Sugahara Erkki Ruoslahti
Published in
G Protein Coupled Receptors - Structure
Each organ and pathology has a unique vascular ZIP code that can be targeted with affinity ligands. In vivo peptide phage display can be used for unbiased mapping of the vascular diversity. Remarkably, some of the peptides identified by such screens not only bind to target vessels but also elicit biological responses. Recently identified tissue-pen...
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Im, Verma Erkki Ruoslahti Lilach Agemy D, Friedmann-Morvinski V. Ramana Kotamraju Lise Roth Kazuki Sugahara Om, Girard Rf, Mattrey
Published in
Proceedings of the National Academy of Sciences
Antiangiogenic therapy can produce transient tumor regression in glioblastoma (GBM), but no prolongation in patient survival has been achieved. We have constructed a nanosystem targeted to tumor vasculature that incorporates three elements: (i) a tumor-homing peptide that specifically delivers its payload to the mitochondria of tumor endothelial ce...