Journal of Gastrointestinal & Digestive System
Open Access

Research Article

Novel Dual Magnetic Drug Targeting and Hyperthermia Therapy in Hepatocellular Carcinoma with Thermosensitive Polymer-Coated Nanoparticles

Chang PEJ^1,6*, Purushotham S², Rumpel H³, Kee IHC⁴, Ng RTH⁴, Chow PKH^4-6, Ramanujan RV² and Tan CK^1,6

¹Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore

²School of Materials Science and Engineering, Nanyang Technological University, Singapore

³Department of Diagnostic Radiology, Singapore General Hospital, Singapore

⁴Department of Experimental Surgery, Singapore General Hospital, Singapore

⁵Department of General Surgery, Singapore General Hospital, Singapore

⁶Duke-NUS Graduate Medical School, Singapore

Corresponding Author:

Dr Jason Chang Pik Eu
Department of Gastroenterology and Hepatology
Singapore General Hospital, Outram Road, Singapore 169608
Tel: (+65) 62223322
Fax: (+65) 62273623
E-mail: jason.chang@sgh.com.sg

Received Date: May 26, 2014; Accepted Date: July 28, 2014; Published Date: August 05, 2014

Citation: Chang PEJ, Purushotham S, Rumpel H, Kee IHC, Ng RTH, et al. (2014) Novel Dual Magnetic Drug Targeting and Hyperthermia Therapy in Hepatocellular Carcinoma with Thermosensitive Polymer-Coated Nanoparticles. J Gastroint Dig Syst 4:198. doi:10.4172/2161-069X.1000198

Copyright: © 2014 Chang PEJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Background: Magnetic drug targeting (MDT) uses magnetic fields to localize magnetic nanoparticles (MNP) to tumor. Once localized, applying an alternating magnetic field (AMF) to the MNPs generates heat energy. Poly-N-isopropylacrylamide (PNIPA) is a thermosensitive polymer that contracts when heated, releasing any drugs which are bound to it. Utilizing these properties, MNP coated with PNIPA polymer on to which doxorubicin is loaded can be localized to hepatocellular carcinoma (HCC) with an external magnetic field. Application of an AMF will then generate localized magnetic hyperthermia (MH) within the tumor, thus releasing bound doxorubicin. This study explores this novel drug delivery model which can be used for targeted dual therapy (MDT and MH) of HCC.

Aim: To demonstrate that doxorubicin-loaded-PNIPA-coated-MNP can be delivered intra-arterially to target HCC in a rat model and that heat is generated and doxorubicin is released when an AMF is applied.

Methods: Morris hepatoma cells are implanted into the livers of buffalo rats. HCC development is confirmed on MRI using a specially-constructed rat-MRI coil. 0.5 ml of doxorubicin-loaded-PNIPA-coated-MNP solution is injected into the hepatic artery and localization of MNP in HCC is confirmed with MRI. Rats are sacrificed for histology of liver and other organs. AMF is applied to doxorubicin-loaded-PNIPA-coated-MNP solution and the temperature measured to demonstrate local hyperthermia in vitro. The amount of doxorubicin released is measured by spectrophotometry.

Results: Successful intra-arterial delivery of MNP was confirmed on post-injection MRI. On histology, iron particles were seen in HCC but not in normal liver or other organs. When AMF was applied, temperature of the suspension reached the target temperature of 42°C within 5 minutes and remained within hyperthermia range(42°C-48°C) for 15 minutes. During this period of hyperthermia, 4.7% (~71 μg) of loaded doxorubicin was released.

Conclusions: We have demonstrated in a rat model the feasibility of intra-arterial doxorubicin-loaded-PNIPA-coated-MNP for synergistic dual therapy of HCC using targeted hyperthermia and doxorubicin.

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