Lingyun Zhao

Nanomedicine for oral chemotherapy

Oral chemotherapy is one of the most important issues in 21st century medicine. It may radically change the current regimen of chemotherapy, as well as greatly improve the quality of life of patients. In comparison with the current practice of chemotherapy (i.e., intravenous injection or infusion), which causes high peak above the maximum tolerable drug concentration in the plasma and fast excretion of the drug from the circulatory system, oral chemotherapy can maintain a sustained and mild drug concentration in the circulation to achieve a prolonged exposure of cancerous cells to the drug. This will increase the therapeutic efficacy and decrease the side effects. Moreover, oral chemotherapy is an important step to realize the patients’ dream of ‘chemotherapy at home’, which will greatly improve their quality of life and give hope to those with late-stage cancer, who have been too weak to tolerate any treatment in the current clinical regimen. Oral chemotherapy provides at least a palliative treatment to give them hope and extend their life [1]. Unfortunately, most anticancer drugs, especially those with excellent anticancer effects such as taxanes (paclitaxel and docetaxel), are not orally bioavailable (i.e., not absorbable/interactive in the GI tract). For paclitaxel, for example, the initial studies reported that its oral bioavailability was less than 1% [2]. As we know, our body is so perfectly structured that all important organs are protected from external toxins by the so-called physiological drug barriers, such as the blood–brain barrier and the gastrointestinal (GI) barrier. The molecular basis of the various physiological drug barriers had been unknown until the past decade when understanding of the molecular biology has made significant progress. For oral bioavailability of taxanes, which are the number one seller among the various anticancer drugs and had US

Nanothermotherapy by high performance magnetic nanoparticles.

3.6 billion annual sale in 2006 in

Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia

“Quae medicamenta non sanat; ferrum sanat. Quae ferrum non sanat; ignis sanat. Huae vero ignis non sanat; insanabilia reportari oportet.” (Those diseases which medicines do not cure, the knife cures; those which the knife cannot cure, fire cures; and those which fire cannot cure, are to be reckoned wholly incurable.) Hippocrates of Kos (ca. 460 BC – ca. 370 BC), Western father of medicine

Effect of hyperthermia on invasion ability and TGF-β1 expression of breast carcinoma MCF-7 cells.

Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46°C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment.

Magnetic Nanocomposite Devices for Cancer Thermochemotherapy

The present study aimed to investigate heating-induced alterations of breast cancer cell invasion abilities and the potential mechanisms associated with TGF-β1 expression. MCF-7 cells were heated at 43, 45, 47 and 37 °C for 30 min. In vitro cell invasion ability was evaluated by matrigel invasion assay. The activity of matrix metalloproteinase (MMP)-2/9 was investigated by gelatin zymographic assays. Expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) was investigated by immunocytochemistry and RT-PCR. Apoptosis was analysed by flow-cytometry. The invasive potential of MCF-7 cells was reduced by heating, and MMP-2/9 secretion and enzymatic activity were suppressed. Furthermore, VEGF and TGF-β1 mRNA and proteins were suppressed by hyperthermia. These results suggest that down-regulation of the expression of TGF-β1, EGF and MMPs by hyperthermia probably accounts for the inhibition of the invasive abilities of MCF-7 cells.

Fabrication, characterization and in-vitro cytotoxicity of magnetic nanocomposite polymeric film for multi-functional medical application

Lingyun Zhao1,3, Yuying Wang1,2, Bing Yang1,2, Xiaoyu Xu1,2, Yan Yan1,2, Meijun Huo1,2, Xiaowen Wang1,3,4 and Jintian Tang1,3,4 1Institute of Medical Physics and Engineering, Department of Engineering Physics, Tsinghua University, Beijing, 100084, 2Department of Pharmaceutics, Beijing University of Chinese Medicine, Beijing, 100102, 3Key Laboratory of Particle and Radiation Imaging, Ministry of Education, Tsinghua University, Beijing, 100084 42nd Hospital Affiliated with Tsinghua University, Beijing China

Evaluation on the Feasibility and Safety of Magnetic Stent Hyperthermia for Esophageal Cancer

Cancer comprehensive treatment has been fully acknowledged as it can provide an effective multimodality approach for fighting cancers. In this study, various innovative technologies for cancer treatment including cancer nanotechnology, chemotherapy by sustainable release, as well as magnetic induction hyperthermia (MIH) have been integrated for the purpose of cancer comprehensive treatment. Briefly, such kind of treatment can be realized by applying of the tailored magnetic nanoparticles (MNPs) composite polymeric film. Fe3O4 MNPs acting as the agent for MIH, and anti-cancer drug docetaxel as chemotherapeutic agent were incorporated within the biodegradable polymeric film. Physiochemical characterizations on MNPs and the film have been systematically carried out by various instrumental analyses. Our results demonstrated that the film has been successfully fabricated by the solvent cast method. Hyperthermia could be induced by stimulating the nanocomposite film under an alternative magnetic field (AMF). The incorporation of MNPs, as well as hyperthermia would facilitate the drug release from the polymeric film. The in-vitro cytotoxicity results indicated the bi-modal cancer treatment approach for combined MIH and chemotherapy is more effective than the mono-modal treatment by docetaxel treatment. The magnetic nanocomposite film can realize cancer comprehensive treatment thus has great potential in clinical application.

Magnetic Arterial Embolization Hyperthermia Mediated by Carbonyl Iron Powder for Liver Carcinoma

Magnetic mediated hyperthermia combined with endoscopic placement of a metal stent, which can be termed as magnetic stent hyperthermia (MSH), is a novel locoregional thermotherapy for esophageal cancer. Based on the strategy of MSH, inductive heat can be generated by the esophageal stent upon exposure under an alternative magnetic field (AMF) and therefore the targeted thermotherapy for esophageal cancer can be achieved. In the current work, we conducted systematic research on the feasibility and safety evaluation on the MSH for esophageal cancer. Two types of super-elastic nitinol stents provided by Beijing Institute of Nonferrous Metals, (Beijing, China) were adopted in the study. A commercially available esophageal stent in clinical application with a length of 110mm and a macroscopic diameter of 15mm (type I) was applied to study the heating inductive heating property and the temperature increase within pig’s esophagus.Both in vitro and in vivo investigation has been carried out. Our results suggest that MSH may have clinical significance for esophageal cancer treatment.

Application of Carbonyl Iron Powder as a Novel Mediator for Arterial Embolization Hyperthermia—Feasibility Investigation

Introduction: Magnetic arterial embolizaiton hyperthermia(MAEH) is a novel and very promising localized modality by combining the advantages of magnetic mediated hyperthermia (MMH) and transcatheter arterial embolizaiton (TAE) for liver carcinoma. This study was carried out to investigate the feasibility of carbonyl iron powder (CIP) microparticles as mediators for MAEH. The protocol was approved by institutional animal care and use committee (IACUC) of Tsinghua University. Materials and Methods: CIP microparticles were adopted in the current study. Magnetic property of the CIP was analyzed by the vibrating sample magnetometer (VSM) and inductive heating property was conducted by exposing CIP/Lipiodol suspensions under alternative magnetic field (AMF). In vivo compatibility investigation was performed on Wistar rats by i.v. injection of CIP extracts. VX2 carcinoma-induced rabbit liver tumor models were employed to study the anti-tumor effect of MAEH mediated by CIP/Lipiodol suspensions. Results and Conclusions: CIP demonstrates very good in vivo biocompatibility and ideal inductive heating characteristics under AMF. MAEH mediated by CIP is a safe and effective treatment that can target liver cancers through dual effects of local hyperthermia and arterial embolization. Our investigation provides feasibility study on developing novel and suitable mediator candidature for MAEH.

Hyperthermia inhibits the proliferation and invasive ability of mouse malignant melanoma through TGF-β1

In this study, we proposed carbonyl iron powder (CIP) as a novel mediator for arterial embolization hyperthermia (AEH). In vitro cytotoxicity study with cultured L929 cells was carried out to test the biocompatibility of the CIP. Effect of alternative magnetic field (AMF) on the temperature rise of CIP was performed by exposing the CIP/Lipiodol suspensions under AMF with different field strength. In vivo heating curve of the hepatic artery after transcatheter arterial embolization (TAE) was also conducted by applying New Zealand half lop rabbits as animal model. Cytotoxicity study demonstrated that CIP showed good biocompatibility. Heating curves, both in vitro and in vivo, revealed that CIP possessed ideal property of inductive heating characteristics under AMF. Our findings suggest that CIP is a very promising mediator candidature of AEH for clinical application.