NANOPARTICLE CANCER THERAPY
Methods of potentiating chemotherapy or radiotherapy are disclosed. The methods comprise administering to a subject in need of chemotherapeutic or radiotherapeutic treatment an effective amount of a composition comprising biocompatible nanoparticles under conditions in which the nanoparticles alter one or more cell regulatory mechanisms in cells in which the nanoparticles are localised or other cells. Then one or more doses of a chemotherapeutic or radiotherapeutic treatment are administered to the subject either concurrently with or after the nanoparticles have altered the one or more cell regulatory mechanisms in the cells in which the nanoparticles are localised or other cells. Also disclosed are methods of enhancing the effects of chemotherapy or radiotherapy on a cell population, methods of increasing the amount of strand breaks in DNA in a cell, and methods of inducing cancer cell death.
1 . A method of inducing cancer cell death, the method comprising:
exposing cancer cells to be treated to an effective amount of a nanoparticle composition comprising biocompatible nanoparticles comprising gold, aluminium, carbon, boron, boron nitride, silica, magnesium oxide, titanium, titania, manganese, arsenic, iron-platinum, and/or barium sulfate and having a diameter or longest dimension in the range of 5 nm to 200 nm under conditions in which at least some of the nanoparticles are localised in the cancer cells to form nanoparticle-laden cancer cells and the localised nanoparticles alter one or more cell regulatory mechanisms in the nanoparticle-laden cancer cells or other cells; and
exposing the nanoparticle-laden cancer cells to a chemotherapeutic agent or ionizing radiotherapy concurrently with or after the nanoparticles have altered the one or more cell regulatory mechanisms in the nanoparticle-laden cancer cells or other cells under conditions to cause cancer cell death.
2 . The method of claim 1 , wherein the cancer is selected from the group consisting of breast cancer, prostate cancer, lymphoma, skin cancer, pancreatic cancer, colon cancer, melanoma, malignant melanoma, ovarian cancer, brain cancer, primary brain carcinoma, head-neck cancer, glioma, glioblastoma, liver cancer, bladder cancer, non-small cell lung cancer, head or neck carcinoma, breast carcinoma, ovarian carcinoma, lung carcinoma, small-cell lung carcinoma, Wilms' tumour, cervical carcinoma, testicular carcinoma, bladder carcinoma, pancreatic carcinoma, stomach carcinoma, colon carcinoma, prostatic carcinoma, genitourinary carcinoma, thyroid carcinoma, esophageal carcinoma, myeloma, multiple myeloma, adrenal carcinoma, renal cell carcinoma, endometrial carcinoma, adrenal cortex carcinoma, malignant pancreatic insulinoma, malignant carcinoid carcinoma, choriocarcinoma, mycosis fungoides, malignant hypercalcemia, cervical hyperplasia, leukaemia, acute lymphocytic leukaemia, chronic lymphocytic leukaemia, acute myelogenous leukaemia, chronic myelogenous leukaemia, chronic granulocytic leukaemia, acute granulocytic leukaemia, hairy cell leukaemia, neuroblastoma, rhabdomyosarcoma, Kaposi's sarcoma, polycythemia vera, essential thrombocytosis, Hodgkin's disease, non-Hodgkin's lymphoma, soft-tissue sarcoma, osteogenic sarcoma, primary macroglobulinemia, and retinoblastoma.
3 . The method of claim 1 , wherein the biocompatible nanoparticles are coated.
4 . The method of claim 3 , wherein the biocompatible nanoparticles comprise a metal or metal oxide core and a silica coating.
5 . The method of claim 3 , wherein the biocompatible nanoparticles comprise a metal or metal oxide core and an organic coating.
6 . The method of claim 1 , wherein the biocompatible nanoparticles comprise gold.
7 . The method of claim 1 , wherein the biocompatible nanoparticles comprise aluminium.
8 . The method of claim 1 , wherein the biocompatible nanoparticles have an average size of greater than 200 to 400 nm.
9 . The method of claim 1 , wherein the nanoparticles reduce the expression of thymidylate synthase.
10 . The method of claim 1 , wherein the nanoparticles reduce the expression of ribonucleotide reductase.