Hybridization of Tumor Homing and Mitochondria-Targeting Peptide Domains to Design Novel Dual-Imaging Self-Assembled Peptide Nanoparticles for Theranostic Applications

Abstract A unique dual-targeting dual-imaging peptide-based nanoprobe was successfully designed by investigating the cyclic heptapeptide having Arg-Gly-Asp-Lys-Leu-Ala-Lys sequence composed of RGD homing motif and KALK mitochondria targeting motif linked via amide bond. The designed peptide was further modified through covalent linkage, characterized and self-assembled to form spherical nanoparticles. The novel Cy5.5-SAPD-99mTc nanoparticles were tested in vitro for cytotoxicity, cellular uptake, biocompatibility 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 dual-targeting dual-imaging nanoparticles may serve as an admirable theranostic probe to treat brain tumor glioblastoma multiforme.