Targeting of Tomato Bushy Stunt Virus with a Genetically Fused C-End Rule Peptide

Luca Marchetti; Lorena Simon-Gracia; Chiara Lico; Mariateresa Mancuso; Selene Baschieri; Luca Santi; Tambet Teesalu

doi:10.3390/nano13081428

Targeting of Tomato Bushy Stunt Virus with a Genetically Fused C-End Rule Peptide

Nanomaterials (Basel). 2023 Apr 21;13(8):1428. doi: 10.3390/nano13081428.

Authors

Luca Marchetti^{1

2}, Lorena Simon-Gracia³, Chiara Lico⁴, Mariateresa Mancuso¹, Selene Baschieri⁴, Luca Santi², Tambet Teesalu^{3

5}

Affiliations

¹ Laboratory of Biomedical Technologies, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, ENEA, Casaccia Research Center, Via Anguillarese 301, 00123 Rome, Italy.
² Department of Agriculture and Forest Sciences (DAFNE), University of Tuscia, Via S. Camillo De Lellis, 01100 Viterbo, Italy.
³ Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14b, 50090 Tartu, Estonia.
⁴ Laboratory of Biotechnologies, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, ENEA, Casaccia Research Center, Via Anguillarese 301, 00123 Rome, Italy.
⁵ Materials Research Laboratory, University of California, Santa Barbara, CA 93106, USA.

Abstract

Homing peptides are widely used to improve the delivery of drugs, imaging agents, and nanoparticles (NPs) to their target sites. Plant virus-based particles represent an emerging class of structurally diverse nanocarriers that are biocompatible, biodegradable, safe, and cost-effective. Similar to synthetic NPs, these particles can be loaded with imaging agents and/or drugs and functionalized with affinity ligands for targeted delivery. Here we report the development of a peptide-guided Tomato Bushy Stunt Virus (TBSV)-based nanocarrier platform for affinity targeting with the C-terminal C-end rule (CendR) peptide, RPARPAR (RPAR). Flow cytometry and confocal microscopy demonstrated that the TBSV-RPAR NPs bind specifically to and internalize in cells positive for the peptide receptor neuropilin-1 (NRP-1). TBSV-RPAR particles loaded with a widely used anticancer anthracycline, doxorubicin, showed selective cytotoxicity on NRP-1-expressing cells. Following systemic administration in mice, RPAR functionalization conferred TBSV particles the ability to accumulate in the lung tissue. Collectively, these studies show the feasibility of the CendR-targeted TBSV platform for the precision delivery of payloads.

Keywords: C-end rule; Tomato Bushy Stunt Virus; drug delivery systems; homing peptide; neuropilin-1; plant virus nanoparticles.

Grants and funding

This research was funded by the European Regional Development Fund (TT, Project No. 2014-2020.4.01.15-0012), the Estonian Research Council (TT, grants PRG230, PRG1788, and EAG79), EuronanomedII projects ECM-CART and iNanoGun (TT), H2020 MSCA-RISE project Oxigenated (TT), AIRC project NANOCROSS (MM, grant IG20314).