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

Drug Delivery and Translational Research volume 12, pages 1774–1785 (2022)Cite this article

Abstract

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-99mTc 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 99mTc for dual-imaging and enhanced therapeutic efficacy against brain tumor.

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Acknowledgements

The authors are cordially thankful to the Director INMOL, and Dr. Munir Ahmad, INMOL, Lahore-Pakistan, for providing Hot-Lab facilities and access to SPECT/CT camera for animal studies.

Funding

This research work was financially supported by the National Natural Science Foundation of China (No. 21575055).

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Authors and Affiliations

  1. College of Chemistry and Chemical Engineering, Gansu Province, Lanzhou University, Lanzhou-730000, People’s Republic of China

    Syed Faheem Askari Rizvi, Shuai Mu & Haixia Zhang

  2. Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore-54000, Punjab, Pakistan

    Samiah Shahid

Authors
  1. Syed Faheem Askari Rizvi
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  2. Samiah Shahid
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  3. Shuai Mu
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  4. Haixia Zhang
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Contributions

S.F.A.R.: conceptualization; methodology; validation; investigation; writing—original draft. S.S.: formal analysis, visualization, resources. S.M.: validation, visualization. H.Z.: validation; project administration; writing—review and editing; supervision.

Corresponding author

Correspondence to Haixia Zhang.

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All animal studies performed in this study were in accordance with the compliance of the animal ethical committee of the National Institute of Health and National Regulation of China for Care and Use of Laboratory Animals (Lanzhou University, Gansu, China).

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Rizvi, S.F.A., Shahid, S., Mu, S. et al. Hybridization of tumor homing and mitochondria-targeting peptide domains to design novel dual-imaging self-assembled peptide nanoparticles for theranostic applications. Drug Deliv. and Transl. Res. 12, 1774–1785 (2022). https://doi.org/10.1007/s13346-021-01066-6

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Keywords

  • Hybridized peptides
  • Dual-imaging
  • Mitochondria-targeting motif
  • Theranostic agent
  • Glioblastoma multiforme