The characterization and evaluation of cisplatin-loaded magnetite-hydroxyapatite nanoparticles as dual treatment of hyperthermia and chemotherapy for lung cancer therapy

• Main Authors: Jian-Yuan Huang, 黃建元
• Other Authors: Feng-Huei Lin
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/10838293515831673973

博士 === 國立臺灣大學 === 醫學工程學研究所 === 103 === A malignant neoplasm is abnormal cell growth in a tissue and affect human quality of life and lifespan. Lung cancer was the second most commonly estimated cancer case and the first leading cause of cancer death both in human. Therefore, lung cancer brought out over one million death worldwide each year. However, in the era of medical technology developed, the five-year relative survival rates of lung cancer, especially in advanced stage, would not significantly improve. Various chemotherapeutic drugs, such as cisplatin, were widely accepted as a standard first-line treatment for advanced NSCLC (non-small cell lung cancer). However, cisplatin performs excellent treatment, but the drug resistance may be the major obstacle to affect the treatment. This study proposed a micro-emulsion method to synthesize cisplatin-loaded magnetite-hydroxyapatite nanoparticles (mHAp/CDDP) to combine chemotherapy and hyperthermia in one nanoparticle system for lung cancer therapy. Magnetite can act as a thermal seed under an alternating magnetic field for hyperthermia. The loading efficiency of the cisplatin in the synthesized nanoparticles was 22.9%. The major phase of the synthesized mHAP/CDDP nanoparticle was identified as hydroxyapatite by XRD; with where the magnetite and CDDP crystal were precipitated on the surface of hydroxyapatite along [211] and [200], respectively. The individual grain size of synthetic nanoparticles were in the range of 50-80 nm directly under TEM examination. The magnetic particles revealed a superparamagnetic property by SQUID; that could induce heat generation within minutes by an external alternating magnetic field and can be used for hyperthermia application. Moreover, the synthesized nanoparticle can be engulfed by A549 cells through endocytosis process. Therefore, hydroxyapatite can be dissolved in endosome-lysosome hybrid which would be breakdown by osmotic pressure and then cisplatin would escape from the vesicles into nucleus leading A549 cells toward apoptosis via ERK signaling pathway. Based on the results of in vitro and in vivo studies, to combine hyperthermia and chemotherapy in mHAp/CDDP nanoparticle could provide synergistic effect to inhibit A549 proliferation and tumor growth. We believed that the mHAp/CDDP nanoparticles have great potential on lung cancer treatment.