On Oc. 30th Prof. Teesalu gave a Cancer Center lecture series talk “Tumor homing peptides: discovery and applications for precision drug delivery” at Fishman auditorium of the SBP La Jolla campus. The talk was preceded and followed by meetings with the SBP faculty members to discuss strategies on using tumor- and central nervous system homing peptides for development of precision drugs to treat cancer and neurodegenerative diseases.
Lingasamy P, Tobi A, Haugas M, Hunt H, Paiste P, Asser T, Rätsep T, Kotamraju VR, Bjerkvig R, Teesalu T.
Biomaterials. 2019 Oct;219:119373. doi: 10.1016/j.biomaterials.2019.119373. Epub 2019 Jul 19.
We report in Biomaterials the identification and development of a novel homing (affinity targeting) peptide that interacts with two landmark proteins in the extracellular matrix of solid tumors: oncofetal fibronectin extra domain B (FN-EDB) and tenascin-C C domain (TNC-C).
We used peptide phage biopanning to identify a 12-mer targeting peptide (PL1, sequence: PPRRGLIKLKTS) that selectively interacts with both TNC-C and FN-EDB. We showed that PL1-functionalized iron oxide nanoworms and silver nanoparticles home to glioblastoma and prostate carcinoma xenografts and to intradermal angiogenic neovessels induced by VEGF-driving adenovirus. PL-1 targeting can be used to improve therapeutic index of anticancer payloads - treatment of glioblastoma-bearing mice with proapoptotic PL1-functionalized nanoparticles resulted in significant reduction of tumor volume and increased survival. Importantly, PL-1 peptide nanoparticles interacted with TNC-C and FN-EDB-positive areas of cryosections of clinical glioma samples. This study suggests that PL1 peptide may have applications as a specific affinity ligand for targeted delivery of diagnostic and therapeutic compounds to solid tumors. EDB antibodies against FN-EDB and TNC-C are in clinical trials as carriers of cytokines to solid tumors, targeting of cancer with a bispecific peptide may allow for a simpler system and more uniform and robust tumor delivery than can be achieved with monospecific antibodies.
This work was performed in collaboration with the Department of Neurosurgery of Tartu University Clinics and Prof. Rolf Bjerkvig at the University of Bergen.
Link to the abstract of the publication: https://www.ncbi.nlm.nih.gov/pubmed/31374479
Elsevier open access link: https://www.sciencedirect.com/science/article/pii/S0142961219304727?via%3Dihub
PL1 IP is owned by the University of Tartu and is available for licensing.
Image: Lead author of the publication, Prakash Lingasamy (left) and Prof. Tambet Teesalu (right). Photograph: Allan Tobi.
In a collaborative study “Peptide-guided nanoparticles for glioblastoma targeting” published in Journal of Controlled Release we evaluated a novel tumor penetrating peptide that targets cell surface p32, LinTT1 (AKRGARSTA), as a GBM targeting ligand for systemically-administered nanoparticles. LinTT1-functionalization increased tumor homing of iron oxide nanoworms (NWs) across a panel of five GBM models ranging from infiltratively-disseminating to angiogenic phenotypes. LinTT1-NWs homed to CD31-positive tumor blood vessels, including to transdifferentiated endothelial cells, and showed co-localization with tumor macrophages and lymphatic vessels. LinTT1-guided proapoptotic NWs exerted strong anti-glioma activity in two models of GBM, including doubling the lifespan of the mice in an aggressive orthotopic stem cell-like GBM that recapitulates the histological hallmarks of human GBM.
Lead authors of this exciting and potentially translationally relevant study were Pille Säälik and Prakash Lingasamy (both Laboratory of Cancer Biology). This work was performed in collaboration with the Department of Neurosurgery of Tartu University Clinics, team of Dr. Dinorah Friedmann-Morvinski at Tel Aviv University, and Prof. Rolf Bjerkvig at the University of Bergen.
Link to the abstract of the paper: https://www.ncbi.nlm.nih.gov/pubmed/31255690
Säälik P, Lingasamy P, Toome K, Mastandrea I, Rousso-Noori L, Tobi A, Simón-Gracia L, Hunt H, Paiste P, Kotamraju VR, Bergers G, Asser T, Rätsep T, Ruoslahti E, Bjerkvig R, Friedmann-Morvinski D, Teesalu T.
J Control Release. 2019 Jun 27. pii: S0168-3659(19)30328-1. doi: 10.1016/j.jconrel.2019.06.018. [Epub ahead of print].
Karolczak-Bayatti M, Forbes K, Horn J, Teesalu T, Harris LK, Westwood M, Aplin JD.
Nanoscale. 2019 Jun 27;11(25):12285-12295. doi: 10.1039/c8nr10337b.
Asciutto EK, Kopanchuk S, Lepland A, Simón-Gracia L, Aleman C, Teesalu T, Scodeller P
J Phys Chem B, 2019 Mar 7;123(9):1973-1982. doi: 10.1021/acs.jpcb.8b11876. Epub 2019 Feb 27.
Hussain S, Joo J, Kang J, Kim B, Braun GB, She ZG, Kim D, Mann AP, Mölder T, Teesalu T, Carnazza S, Guglielmino S, Sailor MJ, Ruoslahti E..
Nat Biomed Eng. 2018 Feb;2(2):95-103. doi: 10.1038/s41551-017-0187-5. Epub 2018 Jan 22.
Prof. Tambet Teesalu gave an inaugural lecture entitled “Nanomedicine: big opportunities in a small world” in the main hall of the University of Tartu on 14.05.2019.
This establishment of a professorship in nanomedicine at the University of Tartu underlines the importance that the University attributes to this exponentially growing interdisciplinary field of medicine.
Hedi Hunt successfully defended her Ph.D. thesis "Precision targeting of intraperitoneal tumors with peptide-guided nanocarriers" on April 18th, 2019. Her thesis dealt with the development of peptide-guided nanoparticles for therapy and imaging of peritoneal carcinomatosis. We wish Hedi good luck in her future career!
Image: Hedi Hunt and her opponent Professor Pirjo Laakkonen PhD of the University of Helsinki (Finland) during the thesis discussion.
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