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Pharmaceutics 2018, 10(2), 63; https://doi.org/10.3390/pharmaceutics10020063

Dual Acting Polymeric Nano-Aggregates for Liver Cancer Therapy

1
Institute of Science and Technology in Medicine, School of Pharmacy, Keele University, Keele ST5 5BG, UK
2
College of Pharmacy, Mosul University, Mosul 41002, Iraq
3
College of Dentistry, University of Basrah, Basrah 61004, Iraq
*
Author to whom correspondence should be addressed.
Received: 2 May 2018 / Revised: 16 May 2018 / Accepted: 24 May 2018 / Published: 26 May 2018
(This article belongs to the Special Issue Nanotechnology Advances in Cancer Treatment)
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Abstract

Liver cancer treatments are often hindered by poor drug physicochemical properties, hence there is a need for improvement in order to increase patient survival and outlook. Combination therapies have been studied in order to evaluate whether increased overall efficacy can be achieved. This study reports the combined treatment of liver cancer cells with a combination treatment of chemotherapeutic agent paclitaxel and pro-apoptotic protein cytochrome C. In order to administer both agents in a single formulation, a poly(allylamine)-based amphiphile has been fabricated with the incorporation of a hybrid iron oxide-gold nanoparticle into its structure. Here, the insoluble paclitaxel becomes incorporated into the hydrophobic core of the self-assemblies formed in an aqueous environment (256 nm), while the cytochrome C attaches irreversibly onto the hybrid nanoparticle surface via gold-thiol dative covalent binding. The self-assemblies were capable of solubilising up to 0.698 mg/mL of paclitaxel (700-fold improvement) with 0.012 mg/mL of cytochrome C also attached onto the hybrid iron oxide-gold nanoparticles (HNPs) within the hydrophobic core. The formulation was tested on a panel of liver cancer cells and cytotoxicity was measured. The findings suggested that indeed a significant improvement in combined therapy (33-fold) was observed when compared with free drug, which was double the enhancement observed after polymer encapsulation without the cytochrome C in hepatocellular carcinoma (Huh-7D12) cells. Most excitingly, the polymeric nanoparticles did result in improved cellular toxicity in human endothelian liver cancer (SK-hep1) cells, which proved completely resistant to the free drug. View Full-Text
Keywords: combination therapy; drug delivery; liver cancer; paclitaxel; hybrid nanoparticles combination therapy; drug delivery; liver cancer; paclitaxel; hybrid nanoparticles
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Al-Shakarchi, W.; Alsuraifi, A.; Curtis, A.; Hoskins, C. Dual Acting Polymeric Nano-Aggregates for Liver Cancer Therapy. Pharmaceutics 2018, 10, 63.

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