Ikemoto H, Lingasamy P, Anton Willmore AM, Hunt H, Kurm K, Tammik O, Scodeller P, Simón-Gracia L, Kotamraju VR, Lowy AM, Sugahara KN, Teesalu T.

Tumour Biol. 2017 May;39(5):1010428317701628. doi: 10.1177/1010428317701628.

Hyaluronan-binding peptide for targeting peritoneal carcinomatosis


https://www.ncbi.nlm.nih.gov/pubmed/28468593

Abstract

Peritoneal carcinomatosis results from dissemination of solid tumors in the peritoneal cavity, and is a common site of metastasis in patients with carcinomas of gastrointestinal or gynecological origin. Peritoneal carcinomatosis treatment is challenging as poorly vascularized, disseminated peritoneal micro-tumors are shielded from systemic anticancer drugs and drive tumor regrowth. Here, we describe the identification and validation of a tumor homing peptide CKRDLSRRC (IP3), which upon intraperitoneal administration delivers payloads to peritoneal metastases. IP3 peptide was identified by in vivo phage display on a mouse model of peritoneal carcinomatosis of gastric origin (MKN-45P), using high-throughput sequencing of the peptide-encoding region of phage genome as a readout. The IP3 peptide contains a hyaluronan-binding motif, and fluorescein-labeled IP3 peptide bound to immobilized hyaluronan in vitro. After intraperitoneal administration in mice bearing peritoneal metastases of gastric and colon origin, IP3 peptide homed robustly to macrophage-rich regions in peritoneal tumors, including poorly vascularized micro-tumors. Finally, we show that IP3 functionalization conferred silver nanoparticles the ability to home to peritoneal tumors of gastric and colonic origin, suggesting that it could facilitate targeted delivery of nanoscale payloads to peritoneal tumors. Collectively, our study suggests that the IP3 peptide has potential applications for targeting drugs, nanoparticles, and imaging agents to peritoneal tumors.

Sharma S, Kotamraju VR, Mölder T, Tobi A, Teesalu T, Ruoslahti E.

Nano Lett. 2017 Mar 8;17(3):1356-1364. doi: 10.1021/acs.nanolett.6b03815. Epub 2017 Feb 17.

Tumor-Penetrating Nanosystem Strongly Suppresses Breast Tumor Growth


https://www.ncbi.nlm.nih.gov/pubmed/28178415

Abstract

Peritoneal carcinomatosis is present in more than 60% of gastric cancer, 40% of ovarian cancer, and 35% of colon cancer patients. It is the second most common cause of cancer-related mortality, with a median survival of 1 to 3 months. Cytoreductive surgery combined with intraperitoneal chemotherapy is the current clinical treatment, but achieving curative drug accumulation and penetration in peritoneal carcinomatosis lesions remains an unresolved challenge. Here, we used flexible and pH-sensitive polymersomes for payload delivery to peritoneal gastric (MKN-45P) and colon (CT26) carcinoma in mice. Polymersomes were loaded with paclitaxeland in vitro drug release was studied as a function of pH and time. Paclitaxel-loaded polymersomes remained stable in aqueous solution at neutral pH for up to 4 months. In cell viability assay on cultured cancer cell lines (MKN-45P, SKOV3, CT26), paclitaxel-loaded polymersomes were more toxic than free drug or albumin-bound paclitaxel (Abraxane). Intraperitoneally administered fluorescent polymersomes accumulated in malignant lesions, and immunofluorescence revealed an intense signal inside tumors with no detectable signal in control organs. A dual targeting of tumors was observed: direct (circulation-independent) penetration, and systemic, blood vessel-associated accumulation. Finally, we evaluated preclinical antitumor efficacy of paclitaxel-polymersomes in the treatment of MKN-45P disseminated gastric carcinoma using a total dose of 7 mg/kg. Experimental therapy with paclitaxel-polymersomes improved the therapeutic index of drug over free paclitaxel and Abraxane, as evaluated by intraperitoneal tumor burden and number of metastatic nodules. Our findings underline the potential utility of the polymersome platform for delivery of drugs and imaging agents to peritoneal carcinomatosis lesions.

Copyright © 2017 American Chemical Society.

Simon-Gracia L, Hunt H,  Scodeller P, Gaitzsch J, Kotamraju VR, Sugahara KN, Tammik O, Ruoslahti E, Battaglia G, Teesalu T

Biomaterials. 2016 Jul 20;104:247-257. doi: 10.1016/j.biomaterials.2016.07.023. [Epub ahead of print]

iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes.


http://www.sciencedirect.com/science/article/pii/S0142961216303544

Abstract

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. Here we studied whether intraperitoneally administered paclitaxel-loaded iRGD-polymersomes show improved efficacy in the treatment of peritoneal carcinomatosis. First, we demonstrated that the pH-sensitive polymersomes functionalized with RPARPAR (a prototypic CendR peptide) or iRGD internalize in the cells that express NRP-1, and that internalized polymersomes release their cargo inside the cytosol. CendR-targeted polymersomes loaded with paclitaxel were more cytotoxic on NRP-1-positive cells than on NRP-1-negative cells. In mice bearing peritoneal tumors of gastric (MKN-45P) or colon (CT26) origin, intraperitoneally administered RPARPAR and iRGD-polymersomes showed higher tumor-selective accumulation and penetration than untargeted polymersomes. Finally, iRGD-polymersomes loaded with paclitaxel showed improved efficacy in peritoneal tumor growth inhibition and in suppression of local dissemination compared to the pristine paclitaxel-polymersomes or Abraxane.

Our study demonstrates that iRGD-functionalization improves efficacy of paclitaxel-polymersomes for intraperitoneal treatment of peritoneal carcinomatosis.

Copyright © 2016 Elsevier Ltd. All rights reserved.

KEYWORDS: NRP-1; Paclitaxel; Peritoneal carcinomatosis; Polymersomes; Tumor penetrating peptides; iRGD

Aman P. Mann, Pablo Scodeller, Sazid Hussain, Jinmyoung Joo, Ester Kwon, Gary B. Braun, Tarmo Mölder, Zhi-gang She, Venkata Ramana Kotamraju, Barbara Ranscht, Stan rajewski, Tambet Teesalu, Sangeeta Bhatia, Michael J. Sailor, Erkki Ruoslahti  

Nature Communications 7, Article number: 11980, doi: 10.1038/ncomms11980

A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries



http://www.nature.com/ncomms/2016/160628/ncomms11980/full/ncomms11980.html

Abstract

Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by<in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

Copyright © 2016, Rights managed by Nature Publishing Group

King A, Ndifon C, Lui S, Widdows K, Kotamraju VR, Agemy L, Teesalu T, Glazier JD, Cellesi F, Tireli N, Aplin JD, Ruoslahti E, Harris LK 

Science Advances 06 May 2016: Vol. 2, no. 5, e1600349 DOI: 10.1126/sciadv.1600349

 

Tumor-homing peptides as tools for targeting delivery of payloads to the placenta



http://advances.sciencemag.org/content/2/5/e1600349

Abstract

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. Peptide-coated nanoparticles intravenously injected into pregnant mice accumulated within the mouse placenta, whereas control nanoparticles exhibited reduced binding and/or fetal transfer. We used targeted liposomes to efficiently deliver cargoes of carboxyfluorescein and insulin-like growth factor 2 to the mouse placenta; the latter significantly increased mean placental weight when administered to healthy animals and significantly improved fetal weight distribution in a well-characterized model of fetal growth restriction. These data provide proof of principle for targeted delivery of drugs to the placenta and provide a novel platform for the development of placenta-specific therapeutics.

Copyright © 2016, The Authors

 Simón-Gracia L,Hunt H, Scodeller PD, Gaitzsch J, Braun GB, Willmore AA, Ruoslahti E, Battaglia G, Teesalu T

Mol Cancer Ther. 2016 Feb 15. pii:molcanther.0713.2015 [Epub ahead of print]

Paclitaxel-loaded Polymersomes for Enhanced Intraperitoneal Chemotherapy


http://www.ncbi.nlm.nih.gov/pubmed/26880267

Abstract

Peritoneal carcinomatosis is present in more than 60% of gastric cancer, 40% of ovarian cancer, and 35% of colon cancer patients. It is the second most common cause of cancer-related mortality, with a median survival of 1 to 3 months. Cytoreductive surgery combined with intraperitoneal chemotherapy is the current clinical treatment, but achieving curative drug accumulation and penetration in peritoneal carcinomatosis lesions remains an unresolved challenge. Here, we used flexible and pH-sensitive polymersomes for payload delivery to peritoneal gastric (MKN-45P) and colon (CT26) carcinoma in mice. Polymersomes were loaded with paclitaxeland in vitro drug release was studied as a function of pH and time. Paclitaxel-loaded polymersomes remained stable in aqueous solution at neutral pH for up to 4 months. In cell viability assay on cultured cancer cell lines (MKN-45P, SKOV3, CT26), paclitaxel-loaded polymersomes were more toxic than free drug or albumin-bound paclitaxel (Abraxane). Intraperitoneally administered fluorescent polymersomes accumulated in malignant lesions, and immunofluorescence revealed an intense signal inside tumors with no detectable signal in control organs. A dual targeting of tumors was observed: direct (circulation-independent) penetration, and systemic, blood vessel-associated accumulation. Finally, we evaluated preclinical antitumor efficacy of paclitaxel-polymersomes in the treatment of MKN-45P disseminated gastric carcinoma using a total dose of 7 mg/kg. Experimental therapy with paclitaxel-polymersomes improved the therapeutic index of drug over free paclitaxel and Abraxane, as evaluated by intraperitoneal tumor burden and number of metastatic nodules. Our findings underline the potential utility of the polymersome platform for delivery of drugs and imaging agents to peritoneal carcinomatosis lesions.

Copyright © 2016, American Association for Cancer Research.

Braun GB, Sugahara KN, Yu OM, Kotamraju VR, Mölder T, Lowy AM, Ruoslahti E, Teesalu T

J Control Release. 2016 Apr 19. pii: S0168-3659(16)30240-1. doi: 10.1016/j.jconrel.2016.04.027. [Epub ahead of print]

Urokinase-controlled tumor penetrating peptide


http://www.ncbi.nlm.nih.gov/pubmed/27106816

Abstract

Tumor penetrating peptides contain a cryptic (R/K)XX(R/K) CendR element that must be C-terminally exposed to trigger neuropilin-1 (NRP-1) binding, cellular internalization and malignant tissue penetration. The specific proteases that are involved in processing of phage display identified tumor penetrating peptides are not known. Here we design de novo a tumor-penetrating peptide based on consensus cleavage motif of urokinase-type plasminogen activator (uPA). We expressed the peptide, uCendR (RPARSGR↓SAGGSVA, ↓ shows cleavage site), on phage or coated it onto silver nanoparticles and show that it is cleaved by uPA, and that the cleavage triggers binding to recombinant NRP-1 and to NPR-1-expressing cells. Upon systemic administration to mice bearing uPA-overexpressing breast tumors, FAM-labeled uCendR peptide and uCendR-coated nanoparticles preferentially accumulated in tumors tissue. We also show that uCendR phage internalization into cultured cancer cells and its penetration in explants of murine tumors and clinical tumor explants can be potentiated by combining the uCendR peptide with tumor-homing module, CRGDC. Our work demonstrates the feasibility of designing tumor-penetrating peptides that are activated by a specific tumor protease. As upregulation of protease expression is one of the hallmarks of cancer, and numerous tumor proteases have substrate specificities compatible with proteolytic unmasking of cryptic CendR motifs, the strategy described here may provide a generic approach for designing proteolytically-actuated peptides for tumor-penetrative payload delivery.Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS: C-end rule; Neuropilin-1; Silver nanoparticles; Tumor targeting; Urokinase; α(v) integrins

Copyright © 2015. Published by Elsevier B.V.

Paasonen L,Sharma S, Braun GB, Kotamraju VR, Chung TD, She ZG, Sugahara KN, Yliperttula M, Wu B, Pellecchia M, Ruoslahti E, Teesalu T

Chembiochem. 2016 Feb 19. doi: 10.1002/cbic.201500564. [Epub ahead of print]

New p32/gC1qR Ligands for Targeted Tumor Drug Delivery


http://www.ncbi.nlm.nih.gov/pubmed/26895508

Abstract

Cell surface p32, the target of LyP-1 homing peptide, is upregulated in tumors and atherosclerotic plaques and has been widely used as a receptor for systemic delivery of payloads. Here, we identified an improved LyP-1-mimicking peptide (TT1, CKRGARSTC). We used this peptide in a fluorescence polarization-based high-throughput screening of a 50 000-compound chemical library and identified a panel of compounds that bind p32 with low micromolar affinity. Among the hits identified in the screen, two compounds were shown to specifically bind to p32 in multiple assays. One of these compounds was chosen for an in vivo study. Nanoparticles surface-functionalized with this compound specifically adhered to surfaces coated with recombinant p32 and, when injected intravenously, homed to p32-expressing breast tumors in mice. This compound provides a lead for the development of p32-targeted affinity ligands that circumvent some of the limitations of peptide-based probes in guided drug delivery.

Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:cancer; drug delivery; high-throughput screening; nanoparticles; peptides

Willmore AA, Simón-Gracia L, Toome K, Paiste P, Kotamraju VR, Mölder T, Sugahara KN, Ruoslahti E, Vraun GB, Teesalu T.

Nanoscale. 2015 Dec 8. [Epub ahead of pront]


http://www.ncbi.nlm.nih.gov/pubmed/26646247

Abstract
Affinity targeting is used to deliver nanoparticles to cells and tissues. For efficient targeting, it is critical to consider the expression and accessibility of the relevant receptors in the target cells. Here, we describe isotopically barcoded silver nanoparticles (AgNPs) as a tool for auditing affinity ligand receptors in cells. Tumor penetrating peptide RPARPAR (receptor: NRP-1) and tumor homing peptide GKRK (receptor: p32) were used as affinity ligands on the AgNPs. The binding and uptake of the peptide-functionalized AgNPs by cultured PPC-1 prostate cancer and M21 melanoma cells was dependent on the cell surface expression of the cognate peptide receptors. Barcoded peptide-functionalized AgNPs were synthesized from silver and palladium isotopes. The cells were incubated with a cocktail of the barcoded nanoparticles [RPARPAR (R), GKRK (K), and control], and cellular binding and internalization of each type of nanoparticle was assessed by inductively coupled plasma mass spectrometry. The results of isotopic analysis were in agreement with data obtained using optical methods. Using ratiometric measurements, we were able to classify the PPC-1 cell line as mainly NRP-1-positive, with 75 ± 5% R-AgNP uptake, and the M21 cell line as only p32-positive, with 89 ± 9% K-AgNP uptake. The isotopically barcoded multiplexed AgNPs are useful as an in vitro ratiometric phenotyping tool and have potential uses in functional evaluation of the expression of accessible homing peptide receptors in vivo.

Zhang H, Tam S, Ingham ES, Mahakian LM, Lai CY, Tumbale SK, Teesalu T, Hubbard NE, Borowsky AD, Ferrara KW

Biomaterials. 2015 Jul;56:104-13. doi: 10.1016/j.biomaterials.2015.03.043. Epub 2015 Apr 16.


http://www.ncbi.nlm.nih.gov/pubmed/25934284

Abstract
Ultrasound molecular imaging has great potential to impact early disease diagnosis, evaluation of disease progression and the development of target-specific therapy. In this paper, two neuropilin-1 (NRP) targeted peptides, CRPPR and ATWLPPR, were conjugated onto the surface of lipid microbubbles (MBs) to evaluate molecular imaging of tumor angiogenesis in a breast cancer model. Development of a molecular imaging agent using CRPPR has particular importance due to the previously demonstrated internalizing capability of this and similar ligands. In vitro, CRPPR MBs bound to an NRP-expressing cell line 2.6 and 15.6 times more than ATWLPPR MBs and non-targeted (NT) MBs, respectively, and the binding was inhibited by pretreating the cells with an NRP antibody. In vivo, the backscattered intensity within the tumor, relative to nearby vasculature, increased over time during the ∼6 min circulation of the CRPPR-targeted contrast agents providing high contrast images of angiogenic tumors. Approximately 67% of the initial signal from CRPPR MBs remained bound after the majority of circulating MBs had cleared (8 min), 8 and 4.5 times greater than ATWLPPR and NT MBs, respectively. Finally, at 7-21 days after the first injection, we found that CRPPR MBs cleared faster from circulation and tumor accumulation was reduced likely due to a complement-mediated recognition of the targeted microbubble and a decrease in angiogenic vasculature, respectively. In summary, we find that CRPPR MBs specifically bind to NRP-expressing cells and provide an effective new agent for molecular imaging of angiogenesis.

Copyright © 2015 Elsevier Ltd. All rights reserved.

Sugahara KN, Scodeller P, Braun GB, de mendoza TH, Yamazaki CM, luger MD, Kitayama J, Alvarez E, Howell SB, Teesalu T, Ruoslahti E, Lowy AM

J Control Release. 2015 Jun 11;212:59-69. doi: 10.1016/j.jconrel.2015.06.009. [Epub ahead of print]


http://www.ncbi.nlm.nih.gov/pubmed/26071630

Abstract
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 prior to IPC. Here, we explore the utility of iRGD, a tumor-penetrating peptide, for improved tumor-specific penetration of intraperitoneal compounds and enhanced IPC in mice. Intraperitoneally administered iRGD significantly enhanced penetration of an attached fluorescein into disseminated peritoneal tumor nodules. The penetration was tumor-specific, circulation-independent, and mediated by the neuropilin-binding RXXK tissue-penetration peptide motif of iRGD. Q-iRGD, which fluoresces upon cleavage, including the one that leads to RXXK activation, specifically labeled peritoneal metastases displaying different growth patterns in mice. Importantly, iRGD enhanced intratumoral entry of intraperitoneally co-injected dextran to approximately 300% and doxorubicin to 250%. Intraperitoneal iRGD/doxorubicin combination therapy inhibited the growth of bulky peritoneal tumors and reduced systemic drug toxicity. iRGD delivered attached fluorescein and co-applied nanoparticles deep into fresh human peritoneal metastasis explants. These results indicate that intraperitoneal iRGD co-administration serves as a simple and effective strategy to facilitate tumor detection and improve the therapeutic index of IPC for peritoneal carcinomatosis.

Copyright © 2015 Elsevier B.V. All rights reserved.

Pang HB, Braun GB, Friman T, Aza-Blanc P, Ruidiaz ME, Sugahara KN, Teesalu T, Ruoslahti E.

Nat Commun. 2014 Oct 3;5:4904. doi: 10.1038/ncomms5904.


http://www.ncbi.nlm.nih.gov/pubmed/25277522

Abstract

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 peptides penetrate through tumour tissue and have shown utility in enhancing drug delivery into tumours. Here we show, using RNAi screening and subsequent validation studies, that NRP1-mediated endocytosis of CendR peptides is distinct from known endocytic pathways. Ultrastructurally, CendR endocytosis resembles macropinocytosis, but is mechanistically different. We also show that nutrient sensing networks such as mTOR signalling regulate CendR endocytosis and subsequent intercellular transport of CendR cargo, both of which are stimulated by nutrient depletion. As CendR is a bulk transport pathway, our results suggest a role for it in nutrient transport; CendR-enhanced drug delivery then makes use of this natural pathway.

Sugahara KN1, Braun GB2, de Mendoza TH3, Kotamraju VR4, French RP5, Lowy AM6, Teesalu T3, Ruoslahti E3

Mol Cancer Ther. 2014 Nov 12. pii: molcanther.0366.2014. [Epub ahead of print]


http://www.ncbi.nlm.nih.gov/pubmed/25392370

Abstract

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 anti-metastatic effect was mediated by the NRP-binding RXXK peptide motif (CendR motif), and not by the integrin-binding RGD motif. iRGD inhibited migration of tumor cells and caused chemorepulsion in vitro in a CendR- and NRP-1-dependent manner. The peptide induced dramatic collapse of cellular processes and partial cell detachment, resulting in the repellent activity. These effects were prominently displayed when the cells were seeded on fibronectin, suggesting a role of CendR in functional regulation of integrins. The anti-metastatic activity of iRGD may provide a significant additional benefit when this peptide is used for drug delivery to tumors.

Copyright © 2014, American Association for Cancer Research.

Hu Q, Chen R, Teesalu T, Ruoslahti E, Clegg DO.
Stem Cells Transl Med. 2014 Oct 8. pii: sctm.2014-0038.

Braun GB, Friman T, Pang HB, Pallaoro A, de Mendoza TH, Willmore AM, Kotamraju VR, Mann AP, She ZG, Sugahara KN, Reich NO, Teesalu T, Ruoslahti E.
Nat Mater. 2014 Jun 8. doi: 10.1038/nmat3982.

Hong-Bo Pang, Gary B. Braun, Zhi-Gang She, Venkata R. Kotamraju, Kazuki N. Sugahara, Tambet Teesalu, Erkki Ruoslahti
J Control Release. 2014 Feb 10;175:48-53. doi: 10.1016/j.jconrel.2013.12.006. Epub 2013 Dec 15.

Sánchez-Martín D, Martínez-Torrecuadrada J, Teesalu T, Sugahara KN, Alvarez-Cienfuegos A, Ximénez-Embún P, Fernández-Periáñez R, Martín MT, Molina-Privado I, Ruppen-Cañás I, Blanco-Toribio A, Cañamero M, Cuesta AM, Compte M, Kremer L, Bellas C, Alonso-Camino V, Guijarro-Muñoz I, Sanz L, Ruoslahti E, Alvarez-Vallina L
Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13791-6. doi: 10.1073/pnas.1300013110. Epub 2013 Aug 5

Tumor-penetrating peptides

Tuesday, 05 November 2013 14:37

Teesalu T, Sugahara KN, Ruoslahti E
Front. Oncol., 27 August 2013 | doi: 10.3389/fonc.2013.00216

Zanuy D, Kotla R, Nussinov R, Teesalu T, Sugahara KN, Alemán C, Haspel N.
J Struct Biol. 2013 Feb 24. doi:pii: S1047-8477(13)00043-9. 10.1016/j.jsb.2013.02.006. [Epub ahead of print]

Missirlis D, Teesalu T, Black M, Tirrell M.
PLoS One. 2013;8(1):e54611. doi: 10.1371/journal.pone.0054611. Epub 2013 Jan 17.

Chen R, Braun GB, Luo X, Sugahara KN, Teesalu T, Ruoslahti E.
Cancer Res. 2013 Feb 15;73(4):1352-61. doi: 10.1158/0008-5472.CAN-12-1979. Epub 2012 Dec 17.

Alberici L, Roth L, Sugahara KN, Agemy L, Kotamraju VR, Teesalu T, Bordignon C, Traversari C, Rizzardi GP, Ruoslahti E.
Cancer Res. 2013 Jan 15;73(2):804-12. doi: 10.1158/0008-5472.CAN-12-1668. Epub 2012 Nov 14.

Teesalu T, Sugahara KN, Ruoslahti E.
Methods Enzymol. 2012;503:35-56. doi: 10.1016/B978-0-12-396962-0.00002-1.