Method for tumor detection and targeted hyperthermia

Abstract

The present invention provides stem cells loaded with bi-functional magnetic nanoparticles (nanoparticle-loaded stem cells (NLSC)) that both: a) heat in an alternating magnetic field (AMF); and b) provide MRI contrast enhancement for MR-guided hyperthermia. The nanoparticles in the NLSC are non-toxic, and do not alter stem cell proliferation and differentiation, the nanoparticles do however, become heated in an alternating magnetic field, enabling therapeutic applications for cancer treatment. Due to the fact that circulating stem cells home to tumors and metastasis, and participate in neovascularization of growing tumors, the NLSC of the present invention allows tracking of the tissue distribution of infused stem cells and selective heating of targeted tissues with AMF. NLSC can deliver hyperthermia to hypoxic areas in tumors for sensitization of those areas to subsequent treatment, thus delivering therapy to the most treatment-resistant tumor regions. The heating of diseased tissue either results in direct cell killing or makes the tumor more susceptible to radio- and/or chemotherapy. The targeted hyperthermia provided by the present invention has clinical potential because it is associated with fewer side effects, and can also be used in combination with conventional treatment modalities, significantly enhancing their effectiveness. The NLSC of the present invention can be used for MR image-guided hyperthermia in oncology, in stem cell research for cell tracking and heating, and for elimination of mis-injected stem cells.

1 - 18 . (canceled) 
     
     
         19 . A method for treating a tumor in a subject, comprising:
 a) administering intravenously to the subject an amount of mesenchymal stem cells loaded with bi-functional nanoferrite magnetic nanoparticles; and   b) allowing sufficient time for the mesenchymal stem cells loaded with the bi-functional nanoferrite magnetic nanoparticles to localize to the tumor.   
     
     
         20 . The method of  claim 19 , further comprising:
 c) detecting the tumor by imaging the mesenchymal stem cells loaded with the bi-functional nanoferrite magnetic nanoparticles localized at the tumor through magnetic resonance imaging (MM).   
     
     
         21 . The method of  claim 20 , wherein the tumor is a solid tumor. 
     
     
         22 . The method of  claim 21 , wherein the solid tumor is alveolar rhabdomyosarcoma, bone cancer, brain cancer, breast cancer, cancer of anus, anal canal, or anorectum, cancer of eye, cancer of intrahepatic bile duct, cancer of joints, cancer of neck, gallbladder, or pleura, cancer of nose, nasal cavity, or middle ear, cancer of oral cavity, cancer of vulva, colon cancer, esophageal cancer, cervical cancer, gastrointestinal carcinoid tumor, hypopharynx cancer, kidney cancer, larynx cancer, liver cancer, lung cancer, malignant mesothelioma, melanoma, nasopharynx cancer, ovarian cancer, pancreatic cancer, peritoneum, omentum, and mesentery cancer, pharynx cancer, prostate cancer, rectal cancer, renal cancer, renal cell carcinoma (RCC), small intestine cancer, soft tissue cancer, stomach cancer, testicular cancer, thyroid cancer, ureter cancer, or urinary bladder cancer. 
     
     
         23 . The method of  claim 20 , wherein the tumor is a metastatic tumor. 
     
     
         24 . The method of  claim 19 , wherein the mesenchymal stem cells loaded with the bi-functional nanoferrite magnetic nanoparticles localize to a hypoxic region in the tumor. 
     
     
         25 . The method of  claim 24 , wherein the mesenchymal stem cells loaded with the bi-functional nanoferrite magnetic nanoparticles participate in tumor vasculature formation. 
     
     
         26 . The method of  claim 19 , further comprising: administering a pharmaceutical composition comprising one or more chemotherapeutic agents before or after the mesenchymal stem cells loaded with the bi-functional nanoferrite magnetic nanoparticles are localized at the tumor. 
     
     
         27 . The method of  claim 26 , wherein the one or more chemotherapeutic agents are cell-cycle specific agent, cell-cycle nonspecific agent, alkylating agent, angiogenesis inhibitor, aromatase inhibitor, antimetabolite, anthracycline, antitumor antibiotic, antibody, platinum agent, topoisomerase inhibitor, plant alkaloid, radioisotope or radionuclide. 
     
     
         28 . The method of  claim 26 , wherein the one or more chemotherapeutic agents are administered after the mesenchymal stem cells loaded with the bi-functional nanoferrite magnetic nanoparticles are localized at the tumor. 
     
     
         29 . The method of  claim 19 , wherein the bi-functional nanoferrite magnetic nanoparticles comprise magnetite. 
     
     
         30 . The method of  claim 19 , wherein the mesenchymal stem cells comprise stem cells selected from the group consisting of autologous stem cells and allogenic stem cells. 
     
     
         31 . The method of  claim 30 , wherein the autologous stem cells are selected from the group consisting of: a) cells derived from circulation or endothelial progenitor cells; b) cells derived from bone marrow; and c) cells obtained from cell banks. 
     
     
         32 . The method of  claim 30 , wherein the allogenic stem cells are selected from the group consisting of: a) cells derived from non-embryonic tissues or adult stem cells; and b) cells derived from human embryonic stem cell (hESC) lines from in vitro fertilization (IVF) embryos. 
     
     
         33 . The method of  claim 19 , wherein the bi-functional nanoferrite magnetic nanoparticles comprise a biocompatible coating. 
     
     
         34 . The method of  claim 19 , wherein the mesenchymal stem cells are isolated from the subject and expanded in cell culture. 
     
     
         35 . The method of  claim 19 , wherein the mesenchymal stem cells are isolated from an allogeneic donor and expanded in cell culture. 
     
     
         36 . The method of  claim 19 , wherein the mesenchymal stem cells loaded with the bi-functional nanoferrite magnetic nanoparticles are incorporate into the primary tumor or metastasis tumor with active vasculature formation. 
     
     
         37 . The method of  claim 19 , further comprising: monitoring homing and progression of the mesenchymal stem cells loaded with the bi-functional nanoferrite magnetic nanoparticles in the tumor. 
     
     
         38 . The method of  claim 19 , further comprising: administering a radiotherapy before or after the mesenchymal stem cells loaded with the bi-functional nanoferrite magnetic nanoparticles are localized at the tumor.