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
Affiliations
Luca Marchetti
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
Lorena Simon-Gracia
Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14b, 50090 Tartu, Estonia
Chiara Lico
Laboratory of Biotechnologies, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, ENEA, Casaccia Research Center, Via Anguillarese 301, 00123 Rome, Italy
Mariateresa Mancuso
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
Selene Baschieri
Laboratory of Biotechnologies, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, ENEA, Casaccia Research Center, Via Anguillarese 301, 00123 Rome, Italy
Luca Santi
Department of Agriculture and Forest Sciences (DAFNE), University of Tuscia, Via S. Camillo De Lellis, 01100 Viterbo, Italy
Tambet Teesalu
Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14b, 50090 Tartu, Estonia
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.
