Biocompatibility study of P (N-isopropylacrylamide)-based nanocomposite and its cytotoxic effect on HeLa cells as a drug delivery system for Cisplatin

Abstract

Cisplatin (CDDP) is widely used as an effective drug in the treatment of various cancers. In spite of its therapeutic effects, there are disadvantages in using CDDP, including causing toxicity in healthy cells, also tumor cells become resistant in prolonged use. The use of magnetic nanogels (nanocomposite), as a drug delivery system, can be a potential strategy to overcome these disadvantages. In this study, the biocompatibility (hemocompatibility and cytocompatibility) of the magnetic, pH, and thermo-responsive poly (N-isopropylacrylamide-co-N, N-dimethylaminoethyl methacrylate-co-4-acrylamidofluorescein)-Fe3O4 nanocomposite was assessed in normal cells. Moreover, we evaluated the cytotoxicity, apoptosis, and drug-resistant genes expression of CDDP-loaded nanocomposite against free CDDP in the cervical cancer cell line (HeLa cells) to investigate its potentials as a vector for drug delivery. The results exhibited that the prepared nanocomposite had an appropriate hemocompatibility. Also, the nanocomposite displayed a good cytocompatibility using LDH test. In addition, the MTT assay of the blank nanocomposite, free CDDP, and CDDP-loaded nanocomposite in the HeLa cells indicated that the blank nanocomposite, had no cytotoxic effects on the cells. However, the Free CDDP and CDDP-loaded nanocomposites demonstrated considerable amount of cytotoxicity effect on the HeLa cells (p < 0.05). The results from the Real Time PCR illustrated that the CDDP-loaded nanocomposite could increase the expression of apoptosis genes and reduce the expression of drug resistance genes in the cancer cells. Our data suggested that the synthetized nanocomposite could be used as an effective and biocompatible drug delivery system for smart delivery and intravenous administration of CDDP. Literature mining-based network discovery proposed candidates for tumor sensitivity/resistance to Cisplatin, viz NR4A1, NR1I2, TP73, and TP53 transcription factors as well as EDN1, CD40LG, INS, and TNFSF11 secreted ligands.