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As chemo-radiotherapy continues to increase the lifespan of patients with nasopharyngeal carcinoma (NPC), adverse reaction and drug resistance remain two major problems when using cisplatin (CDDP). In this study, we took the lead in designing a dual-mechanism anti-cancer system modified with cell-penetrating peptide on the surface of superparamagnetic iron oxide nanoparticles (SPION) to enhance CDDP delivery efficacy to NPC cells, especially CDDP resistant NPC cells. The combinatorial delivery of CDDP and iron oxide nanoparticles showed an unexpected effect on reversal of CDDP resistance due to the Fenton reaction with an average decrease in the half maximal inhibitory concentration (IC 50) of 85% and 94% in HNE-1/DDP and CNE-2/DDP resistant cells respectively compared to CDDP alone. On this basis, modification with TAT peptide (YGRKKRRQRRR) significantly improved tumor intracellular uptake, devoting to better curative effects and minimized side effects by reducing CDDP therapeutic doses. Furthermore, we specifically labelled CDDP with fluorescence for detection of intracellular nanoparticles uptake and mechanism research through drug tracing. This novel compound provides a promising therapy for reducing chemotherapy side effects and reversing CDDP-resistant nasopharyngeal carcinoma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A prodrug gelation strategy was developed for the sustained and dual stimuli-response release of doxorubicin hydrochloride (DOX·HCl), a commonly used anticancer drug. For this purpose, the chemical conjugation of DOX·HCl onto thiolated hyaluronic acid (HA) was carried out by an acid liable hydrazone linkage and verified by (1)H NMR analyses. When exposed to the air, such a polysaccharide conjugate showed unique self-gelation ability in aqueous solution. The gelation time and extent depended mainly on the content of thiol groups on thiolated HA. The resultant hydrogel exhibited a dominant elastic response and a thixotropic property. In particular, it could release sustainably conjugated DOX·HCl in dual pH- and reduction-responsive modes. The cumulative drug release was found to be significantly accelerated under the conditions mimicking the intracellular environments of cancer cells. The in vitro cytotoxicity assays for the human nasopharyngeal carcinoma CNE2 cells treated with various release media confirmed the effectiveness of this conjugate hydrogel for cancer cell inhibition., (Copyright © 2015 Elsevier Ltd. All rights reserved.)