## 1 Introduction  
Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer mortality in men in Western countries [1]. Current management options for prostate cancer include watchful waiting, surgery, cryosurgery, radiation therapy, hormonal therapy, and chemotherapy. Choosing the best treatment for localized or locally advanced prostate cancer is based on the age, stage, grade of the tumor, general health and evaluation of the risk and benefit. Because prostate cancer cell growth is dependent on androgen, androgen-deprivation therapy (ADT) is used for men with advanced disease and results in suppression of the disease for many years. However, long-term ADT results in progression to a stage referred to as castration-resistant prostate cancer (CRPC), which may present as either a continuous rise the serum prostate-specific antigen (PSA)levels, the progression of pre-existing disease, and/or the occurrence of metastatic disease. Treatments for patients with CRPC have changed dramatically with the development of drugs targeting the androgen receptor axis (abiraterone and enzalutamide) and a new taxane (cabazitaxel) [2]. However, docetaxel (DTX)-based chemotherapy is now considered the standard treatment for patients with CRPC and detectable metastatic disease. The current regimen requires administration of high doses of DTX, which induces toxic reactions; thus, combination of DTX with other agents is difficult. Acquired resistance to DTX-based therapy has also been observed [3]. To improve the survival and quality of life of patients with CRPC, it is necessary to modify classical chemotherapies and develop new combination therapies, as well as develop novel therapeutic strategies targeting the molecular basis of CRPC.  
Nanomaterials, which are at the leading edge of the developing field of nanotechnology, offer great potential in medicine and pharmacology. Among nanomaterials, nanoparticles (NPs) are defined as ranging in length from 1 to 100 nm in two or three dimensions and show different properties from those of the bulk material [4]. Among various types of NPs, iron oxide (Fe\({}_{3}\)O\({}_{4}\) and \(\gamma\)-Fe\({}_{2}\)O\({}_{3}\)) NPs, which have biocompatible and superparamagnetic properties, appear particularly promising. Importantly, NPs exhibit the superparamagnetism phenomenon, i.e., they become magnetized up to their saturation magnetization in an external magnetic field but do not exhibit any residual magnetic interaction out of the magnetic field [5]. These magnetic iron oxide NPs have immense potential in a variety of biomedical applications, such as drug delivery, magnetofection, hyperthermia, and magnetic resonance imaging [5]. In addition to these properties, these NPs have been shown to have cytotoxicity in cancer cells [6; 7]. Combination of Fe\({}_{3}\)O\({}_{4}\) NPs with chemotherapeutic agents has been also applied for leukemia, lung cancer, pancreatic cancer, and prostate cancer cells [8; 9; 10; 11; 12]. However, Fe\({}_{3}\)O\({}_{4}\) NPs had little or no effect on normal cells as same as previous studies [6; 12]. In addition, combined application of Fe\({}_{3}\)O\({}_{4}\) NPs with other chemotherapeutic drugs may pave the way for reuse of chemotherapeutic drugs, such as platinum compounds and mammalian target of rapamycin (mTOR) inhibitors.  
In this study, we aimed to clarify the combined effects of Fe\({}_{3}\)O\({}_{4}\) NPs and chemotherapeutic agents (rapamycin and carboplatin) for prostate cancer cell growth in vitro.