The Development of a Nano-based Approach to Alleviate Cisplatin-Induced Ototoxicity

Abstract

Cisplatin-induced hearing loss is experienced by a high percentage of patients with squamous cell carcinoma undergoing cisplatin chemotherapy. A novel nano-construct capable of sequestering extracellular cisplatin was developed to combat this problem. The nano-construct consisted of superparamagnetic iron oxide nanoparticles (SPIONs) entrapped within polymeric micelles, which were formed from a glutathione diethyl ester-conjugated amphiphilic diblock copolymer. The glutathione-micelles were analyzed at the cellular level and in an organotypic study for safety evaluation. All utilized methods indicated that the micelles do not cause cellular toxicity or organ damage. The micelles' ability to reduce cisplatin-induced cytotoxicity was then probed in an in vitro model. Cisplatin was pre-treated with the novel nano-construct before being added to growing cells. When compared to cells that were exposed to untreated cisplatin, cells in the pre-treated cisplatin group showed a significant increase in cell viability. This clearly demonstrates that the construct is able to protect the cells from cisplatin cytotoxicity and makes it highly likely that the novel nano-construct will be able to play a role in the protection of the inner ear from cisplatin-induced ototoxicity.

Use of Super Paramagnetic Iron Oxide Nanoparticles as Drug Carriers in Brain and Ear: State of the Art and Challenges

“…Polyethylene glycol (PEG) provides both hydrosoluble and liposoluble characteristics to the particles, maintains electroneutrality, and avoids recognition by the reticulo-endothelial system to increase blood circulation time [ 107 ]. These properties have been exploited in multiple studies [ 18 , 40 , 47 , 50 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ]. The efficiency of doxorubicin (DOX) and indocyanine green loaded on 1,2- distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG-SPIONS (SPION@DSPE-PEG/DOX/ICG) was compared to free DOX and SPION@DSPE-PEG NPs on glioma tumors in rats (n = 38) after the confirmation of their in vitro biocompatibility [ 66 ].…”

“…Polymers derived from amino acids were considered as SPIONs coating to increase their biocompatibility: gluthatione [ 58 , 62 ], glycine [ 82 ], glutamic acid [ 82 ], collagen [ 82 ], human serum albumin [ 18 , 82 ], aminosilane [ 112 ], and spermine [ 90 ] ( Table 2 ). The ability to cross a model of BBB in vitro of 5 SPIONs with different coatings in this category: 1—glycine, glutamic acid, bovine serum albumin (GGB), 2—glycine, glutamic acid, collagen (GGC), 3—glycine, glutamic acid, polyvinyl alcohol (GGP), 4—bovine serum albumin, polyethylene glycol (BPC), 5—collagen, polyvinyl alcohol, bovine serum albumin (CPB) showed that CPB-SPIONs, coated with collagen, have the highest in vitro cellular uptake and the best diffusion levels through BBB (2.7 g/mL of CPB were found after 2 h in the receiving well by a Ferrozine assay kit versus 1.9 of BPC and GGP, versus 1.5 of GGB, and versus 1.7 of GGC) [ 82 ].…”

“…Polymers derived from lipids (oleic acid [ 76 , 81 , 112 ], micelles [ 48 , 62 ], DSPE [ 50 , 113 ], phospholipid [ 66 ], DMPC [ 69 ], and lipophilic fluorescence dye [ 111 ]) show good biocompatibility and capacity to cross biological barriers ( Table 2 ). SPIONs coated by a lipophilic fluorescence dye were studied in vitro to evaluate their capacity to cross brain capillary endothelial cells (BCECs) with or without an external magnet with a field strength of 0.39 tesla [ 111 ].…”

“…In order to reach the inner ear, SPIONs could be driven by an EMF though the round window [ 45 , 79 ], using a cochleostomy [ 44 ] or deposited in the middle ear for passive diffusion through the round window [ 111 ]. In vitro, an EMF was used to increase the migration of SPIONs in cochlear cells [ 62 , 96 ]. After verifying the absence of toxicity of NPs on cells derived from the inner ear (EC5V), the NPs were injected through a cochleostomy into the inner ear of guinea pigs [ 44 ].…”

Cisplatin combined with laser‑activated nanotherapy as an adjuvant therapy for head and neck cancer

“…Nanoparticles and nanomaterials have been used in the treatment of cancer to enhance targeted drug delivery and tumor specificity to minimize side-effects (28)(29)(30)(31)(32). The present study focuses on a particular class of laser-activated nanoparticles, specifically, a thermal ablation platform therapy using near-infrared excitation of gold nanorods (AuNRs), laser-activated nanotherapy (LANT).…”