Abstract

Introduction: Chemotherapy is one of the most effective therapy available to treat cancers, but the side effects make it less favourable. Therefore, we aimed to effect selective and targeted delivery of cisplatin to cancer cell via covalent-modification of zeolitic imidazolate framework-90 (ZIF-90) with RGD peptide, a tripeptide that was known for its ability to recognise integrins on cell surface. Due to overexpression of integrins by cancer cell, RGD peptide on the surface of ZIF-90 would be able to guide the delivery of the cancer drug (cisplatin) encapsulated in the pores of ZIF-90, to the intended recipient. Thus, side effect to normal cells will diminish. Methods: Nano-sized ZIF-90 encapsulated cisplatin (RGD@Cis⊂nZIF-90) was prepared by in-situ encapsulation followed by covalent modification with RGD peptide. The drug loading amount and drug released was profiled, and MTT assay on MRC-5 (human fetal lung fibroblast cells) and A549 (lung adenocarcinoma) cells was conducted. Results: Powder XRD confirmed the formation of ZIF-90 and covalent bond to RGD peptide was confirmed with NMR and IR showing formation of imine bond between imidazolcarbaldehyde linker of ZIF-90 and the RGD peptide. The cisplatin loading was measured to be 24.8% using UV-vis and sustained released behaviour at pH 5 was observed with maximum released (92%) observed after 24 hours. The MTT assay showed that RGD@Cis⊂nZIF-90 nanoparticle was more toxic towards A549 (IC50 8.79 μgmL-1) than MRC-5 (IC50 31.07 μgmL-1). The selectivity index was found to be 3.5 suggesting that there is selectivity towards A549 cell in the presence of RGD peptide. Conclusion: RGD-modified nano-sized ZIF-90 encapsulated cisplatin has been successfully synthesized and determined to have good selectivity and toxicity towards lung cancer cell over normal cell. This may lead to more selective and improve performance of cancer therapy with little side effect.

Keywords: ZIF-90, RGD peptide, cisplatin, selective chemotheraphy, cancer drug delivery