Bi-specific tenascin-C and fibronectin targeted peptide for solid tumor delivery

Lingasamy, Prakash; Tobi, Allan; Haugas, Maarja; Hunt, Hedi; Paiste, Päärn; Asser, Toomas; Rätsep, Tõnu; Kotamraju, Venkata Ramana; Bjerkvig, Rolf; Teesalu, Tambet

doi:10.1016/j.biomaterials.2019.119373

Cited by 42 publications

(51 citation statements)

References 41 publications

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“…Briefly, the multiwell plates were coated with 20 µg/ml recombinant TNC-C in 100 µl of PBS overnight at 4 °C, followed by blocking with 1% bovine serum albumin (BSA) in PBS overnight at 4 °C. The phage library (5 × 10 8 pfu in 100 µl of PBS-BSA) was incubated overnight at 4 °C, followed by 6 washes with PBS containing 1% BSA and 0.1% Tween-20 (washing buffer) to remove background phages, and by phage rescue and amplification in E. coli strain BLT5403 (Novagen, EMD Biosciences, MA, USA) 8 . The subsequent rounds of selection were performed on Ni-NTA Magnetic Agarose Beads (QIAGEN, Hilden, Germany) coated with His-6X tagged TNC-C (30 µg/10 µl beads) at room temperature for 1 h in 400 µl of PBS.…”

Section: Methodsmentioning

confidence: 99%

“…Nanoparticle synthesis and functionalization. The iron oxide nanoworms (NWs) were prepared according to a published protocol by 8,26,27 . The aminated NWs were PEGylated using maleimide-5K-PEG-NH.…”

Section: Methodsmentioning

confidence: 99%

“…Peptides were coupled to NWs through a thioether bond between the thiol group of a cysteine residue added to the N-terminus of the peptide. The concentration of the NWs was determined by measuring the absorbance of NWs at 400 nm with a NanoDrop 2000c spectrophotometer (Thermo Scientific) 8,27 . Silver nanoparticles (AgNPs) were synthesized and functionalized as described 28 , CF647-N-hydroxysuccinimide-dye (NHS-dye) was conjugated to the PEG terminal amine groups, and biotinylated peptides were coated on the NeutrAvidin (NA) on the surface of the AgNPs.…”

Section: Methodsmentioning

confidence: 99%

“…Tenascin C (TNC) is an ECM glycoprotein that is upregulated during normal tissue repair and in many human malignancies and plays important roles in tumor neovascularization, modulation of adhesion, and local and distant motility of malignant cells, and modulation of tumor immune status 4 . Several affinity ligands of TNC have been developed for targeting payloads to solid tumors, such as G11 single-chain antibody 5 , aptamers 6 , FH peptide 7 , and PL1 peptide 8 . TNC targeting antibodies are in phase I/II/ III clinical trials as affinity targeting modules for cytotoxic or immunomodulatory payloads for therapy of solid tumors including metastatic renal cell carcinoma, metastatic melanoma, pancreatic carcinoma, acute myeloid leukemia, sarcoma and breast carcinoma, lung cancer, colorectal cancer, and glioma 4 .…”

mentioning

confidence: 99%

“…Importantly, malignant transformation is not only able to increase the expression of tenascin-C, but also influence its qualitative composition by modulating the splicing to result in different proportion of its isoforms. In particular, 91-amino acid alternatively spliced type-III homology domain of Tenascin-C FnIII C (TNC-C) has a tumor-restricted expression pattern 5,8,9 . The TNC-C is abundant in the glial tumors of the CNS, as well as in various carcinomas [10][11][12] .…”

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confidence: 99%

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Tumor-penetrating peptide for systemic targeting of Tenascin-C

Lingasamy

Tobi

Kurm

et al. 2020

Sci Rep

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Extracellular matrix in solid tumors has emerged as a specific, stable, and abundant target for affinityguided delivery of anticancer drugs. Here we describe the homing peptide that interacts with the C-isoform of Tenascin-C (TNC-C) upregulated in malignant tissues. TNC-C binding PL3 peptide (amino acid sequence: AGRGRLVR) was identified by in vitro biopanning on recombinant tnc-c. Besides tnc-C, PL3 interacts via its C-end Rule (CendR) motif with cell-and tissue penetration receptor neuropilin-1 (NRP-1). Functionalization of iron oxide nanoworms (NWs) and metallic silver nanoparticles (AgNPs) with PL3 peptide increased tropism of systemic nanoparticles towards glioblastoma (GBM) and prostate carcinoma xenograft lesions in nude mice (eight and five-fold respectively). Treatment of gliomabearing mice with proapoptotic PL3-guided NWs improved the survival of the mice, whereas treatment with untargeted particles had no effect. PL3-coated nanoparticles were found to accumulate in TNC-C and NRP-1-positive areas in clinical tumor samples, suggesting a translational relevance. The systemic tumor-targeting properties and binding of PL3-NPs to the clinical tumor sections, suggest that the PL3 peptide may have applications as a targeting moiety for the selective delivery of imaging and therapeutic agents to solid tumors.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Tumor-penetrating peptide for systemic targeting of Tenascin-C

Lingasamy

Tobi

Kurm

et al. 2020

Sci Rep

Self Cite

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ALPPL2‐Binding Peptide Facilitates Targeted mRNA Delivery for Efficient Hepatocellular Carcinoma Gene Therapy

Lei

Chen

Ming

et al. 2022

Adv Funct Materials

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mRNA-based gene therapy has emerged as an advanced strategy for hepatocellular carcinoma (HCC) treatment. However, one of its main limitations is lacking delivery precision in vivo. Distinguishing HCC cells from other tissues is crucial for maintaining the high stability, positive therapeutic outcomes, and safety of mRNA therapeutics. Here, a novel HCC specific peptide HCC167 is developed by phage display. It is shown that the HCC167 peptide can specifically recognize variety of HCC substrates including patient samples with high affinity. Modifying nanoparticles with the HCC167 peptide facilitates an effective HCC active targeting ability. When loading with Bims-encoding mRNA, the systemically administrated DMP-HCC167/Bims complex efficiently suppresses HCC progression in multiple models including patient-derived xenografts. Furthermore, the ALPPL2 protein is identified as a specific binding receptor of the HCC167 peptide on the HCC cell membrane, uncovering a new active targeting mechanism based on the HCC167-ALPPL2 ligand-receptor complex. The binding structure is also investigated by computer-aided modeling. The study hence exhibits a potent active targeting strategy for mRNA-based HCC therapy.

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Homing Peptides for Cancer Therapy

Lingasamy

Teesalu

2021

Advances in Experimental Medicine and Biology

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Bi-specific tenascin-C and fibronectin targeted peptide for solid tumor delivery

Cited by 42 publications

References 41 publications

Tumor-penetrating peptide for systemic targeting of Tenascin-C

Tumor-penetrating peptide for systemic targeting of Tenascin-C

ALPPL2‐Binding Peptide Facilitates Targeted mRNA Delivery for Efficient Hepatocellular Carcinoma Gene Therapy

Homing Peptides for Cancer Therapy

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