Hybridization of tumor homing and mitochondria-targeting peptide domains to design novel dual-imaging self-assembled peptide nanoparticles for theranostic applications

• Published in: Drug delivery and translational research 2022-07, Vol.12 (7), p.1774-1785
• Main Authors: Rizvi, Syed Faheem Askari, Shahid, Samiah, Mu, Shuai, Zhang, Haixia
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Pharmaceutical Sciences/Technology; Short Communication
• ISSN: 2190-393X; 2190-3948
• DOI: 10.1007/s13346-021-01066-6

A novel hybridized dual-targeting peptide-based nanoprobe was successfully designed by using the cyclic heptapeptide. This peptide has Arg-Gly-Asp-Lys-Leu-Ala-Lys sequence, in which the RGD homing motif and KALK mitochondria-targeting motif were linked via amide bond. The designed peptide probe was further modified through covalent linkage to induce dual-imaging functionality, and self-assembled to form spherical nanoparticles. The novel Cy5.5-SAPD- 99m Tc nanoparticles were tested for in vitro cytotoxicity, cellular uptake, and apoptosis-inducing functionalities. The cellular internalization, enhanced cytotoxicity and selective receptor binding capabilities against U87MG cells, excellent dual-imaging potential, improved apoptosis-inducing feature by damaging mitochondria, and in vivo preclinical investigations suggested that our newly designed novel hybridized peptide-based dual-imaging nanoparticles may serve as an admirable theranostic probe to treat brain tumor glioblastoma multiforme. Graphical abstract This study describes the development of dual-targeting self-assembled peptide nanoparticles followed by modifications using NIRF dye and radiolabeled with 99m Tc for dual-imaging and enhanced therapeutic efficacy against brain tumor.