ZIF-90 nanoparticles modified with a homing peptide for targeted delivery of cisplatin

Adamu Abubakar; Emilia Abdulmalek; Wan Norhamidah Wan Ibrahim; Kyle E Cordova; Mohd Basyaruddin Abdul Rahman

doi:10.3389/fchem.2022.1076350

ZIF-90 nanoparticles modified with a homing peptide for targeted delivery of cisplatin

Front Chem. 2022 Dec 5:10:1076350. doi: 10.3389/fchem.2022.1076350. eCollection 2022.

Authors

Adamu Abubakar^{1

2}, Emilia Abdulmalek¹, Wan Norhamidah Wan Ibrahim³, Kyle E Cordova^{4

5

6}, Mohd Basyaruddin Abdul Rahman^{1

5

6}

Affiliations

¹ Integrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia (UPM), Seri Kembangan, Malaysia.
² Department of Chemical Sciences, Taraba State University, P.M.B, Taraba State, Jalingo, Nigeria.
³ Department of Biology, Faculty of Science, UPM, Selangor Darul Ehsan, Malaysia.
⁴ Materials Discovery Research Unit, Advanced Research Centre, Royal Scientific Society, Amman, Jordan.
⁵ Department of Chemistry, Faculty of Science, UPM, Selangor Darul Ehsan, Malaysia.
⁶ Foundry of Reticular Materials for Sustainability (FORMS), Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology, UPM, Selangor Darul Ehsan, Malaysia.

Abstract

To improve the selective delivery of cisplatin (Cis) to cancer cells, we report and establish the significance of active, targeting drug delivery nanosystems for efficient treatment of lung cancer. Specifically, pH-responsive nano-sized zeolitic imidazolate framework (nZIF-90) was synthesized, post-synthetically modified with an Arg-Gly-Asp peptide motif (RGD@nZIF-90), a known cancer cell homing peptide, and loaded with a large amount of Cis (RGD@Cis⊂nZIF-90). RGD@Cis⊂nZIF-90 was shown to be highly stable under physiological conditions (pH = 7.4) with framework dissociation occurring under slightly acidic conditions (pH = 5.0)-conditions relevant to tumor cells-from which 90% of the encapsulated Cis was released in a sustained manner. In vitro assays demonstrated that RGD@Cis⊂nZIF-90 achieved significantly better cytotoxicity (65% at 6.25 μg ml^-1) and selectivity (selectivity index = 4.18 after 48 h of treatment) against adenocarcinoma alveolar epithelial cancer cells (A549) when compared with the unmodified Cis⊂nZIF-90 (22%). Cellular uptake using A549 cells indicated that RGD@Cis⊂nZIF-90 was rapidly internalized leading to significant cell death. After successfully realizing this nanocarrier system, we demonstrated its efficacy in transporting and delivering Cis to cancer cells.

Keywords: RGD; nanocarrier (nanoparticle); peptide; post-synthetic modification (PSM); targeted delivery; zeolitic imidalozate framework.