This is a review article that summarized the research projects undertaken in my lab. It also introduced several related activities from among other groups. Several of our projects have been of interest to public readers. This paper contains much new information and I think this may have been why it has been highly cited. It describes new concepts and methodologies, particularly the concept of nanoparticle self-lighting photodynamic therapy for cancer treatment, the concept of combining photodynamic therapy and radiation therapy for deep cancer treatment, and the applications of nanoparticle photosensitizers for cancer treatment. These are brand new approaches in nanotechnology. In this paper, we introduced several new developments in nanotechnology for biological applications. For example, nanoparticle-based photodynamic therapy is one of the most exciting approaches described in this article. The goal is to find an efficient cancer therapy by developing X-ray luminescence nanoparticles as a light source for photodynamic therapy. Photodynamic therapy has been designated as a "promising new modality in the treatment of cancer" since the early 1980s. Light must be delivered in order to activate photodynamic therapy. Most drugs used for photodynamic therapy require ultraviolet or blue light for activation. Unfortunately, ultraviolet and blue light have minimal penetration into tissue and their application for deep cancer therapy is a problem.
To solve this problem and also to enhance the treatment for deep cancers, we proposed a new photodynamic therapy system in which the light is generated by X-ray luminescence nanoparticles. The X-ray luminescence nanoparticles and afterglow nanoparticles are attached to photoactive drugs and, when the nanoparticle-drug systems are targeted to the tumor and are stimulated by an X-ray during radiotherapy, these nanoparticles will generate light (energy) which activate the drugs for photodynamic therapy. In this case, no direct light delivery to the tumor is necessary and very low doses of radiation are needed. In this modality, the radiation and photodynamic therapies are combined and occur simultaneously, so that the tumor destruction will be more efficient. More importantly, it can be used for deep tumor treatment, as X-rays can penetrate deeply into the tissue. Once demonstrated, this will provide a simple but more efficient modality for breast cancer treatment. I have been working on nanotechnologies for the past 15 years. My original work concentrated on trying to use quantum dots for in vivo imaging, with a concentration on the challenge of light penetration. I also have experience with the design and synthesis scintillation measurement for nanoparticles. I knew light delivery was also a challenging issue for photodynamic therapy, just like in vivo optical imaging. I then arrived at the idea to combine photodynamic therapy with radiation therapy through scintillation nanoparticles for deep cancer treatment. Photodynamic therapy is not new, nor is radiation therapy, but the combination of both through scintillation nanoparticles is new and potentially important for deep cancer treatment. I introduced the concept in a paper published in the Journal of Nanoscience and Nanotechnology in 2006. (Wei Chen and Jun Zhang, "Using Nanoparticles to Enable Simultaneous Radiation and Photodynamic Therapies for Cancer Treatment," Journal of Nanoscience and Nanotechnology 6[4]: 1159-66, April, 2006). Initial results of the studies have been promising. But before "nanoparticle self-lighting photodynamic therapy" becomes a clinical reality, researchers must overcome two main challenges: 1) they need to develop a class of water-soluble scintillation nanoparticles with very high quantum efficiencies of X-ray luminescence, and 2) they need to improve the targeting capabilities of the nanoparticle-photosensitizer compound—but this is a challenge for all drug-based cancer treatments. Most recently, we've used afterglow nanoparticles for photodynamic therapy activation. This is a good solution for improving efficiency since afterglow nanoparticles will maintain their luminescence for a certain period of time after activation. In this case, the radiation dose will be reduced exponentially. This new concept is also introduced in a recent publication: Chen, W. "Nanoparticle self-Lighting photodynamic therapy for cancer treatment," J. Biomed. Nanotechnol 4[4]: 369-76, 2008. This concept is getting more popular and has become intriguing to many investigators. I think this will become quite a hot area during the next decade and that products for practical applications will, sooner or later, be realized. One of our recent review papers has appeared on the ScienceDirect "25 Hottest Articles" list for October—December, 2008: (Juzenas, P., et al.,"Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer," Advanced Drug Delivery Reviews [60]15: 1600-14, December 2008). By the way, many cancer patients and/or their families have contacted me directly and enquired as to the timing for this new modality to become available for patient treatment. I have sensed this urgent need and that is the key motivation for my research. Although there are no obvious political implications for my research, the slowing economy in the USA has really affected the funding of many new scientific projects. Wei Chen, Ph.D. | |||||||
Sunday, May 31, 2009
Combining photodynamic therapy and radiation therapy for deep cancer treatment,
Thursday, March 5, 2009
COMPOSITION AND METHOD FOR CANCER TREATMENT USING TARGETED SINGLE-WALLED CARBON NANOTUBES
| United States Patent Application | 20080227687 |
| Kind Code | A1 |
| Harrison; Roger G. ; et al. | September 18, 2008 |
The present invention is a method for detecting and destroying cancer tumors. The method is based on the concept of associating a linking protein or linking peptide such as, but not limited to, annexin V or other annexins to single-walled carbon nanotubes (SWNT) to form a protein-SWNT complex. Said linking protein or peptide can selectively bind to cancerous cells, especially tumor vasculature endothelial cells, rather than to healthy ones by binding to cancer-specific external receptors such as anionic phospholipids including phosphatidylserine expressed on the outer surfaces of cancer cells only. Irradiation of bound SWNTs with specific wavelength is then used to detect and destroy those cells to which the SWNTs are bound via the linking protein or peptide thereby destroying the tumor or cancer cells.
| U.S. Current Class: | 514/2; 606/3 |
| U.S. Class at Publication: | 514/2; 606/3 |
| Intern'l Class: | A61K 38/00 20060101 A61K038/00; A61B 18/18 20060101 A61B018/18 |
1. A method of treating a cancer tumor or cancer cells in a patient, comprising:
providing a composition comprising a protein-carbon nanotube complex comprising a protein or peptide operatively attached to a carbon nanotube, wherein the protein or peptide of the protein-carbon nanotube complex comprises a binding protein or peptide that has binding specific for an external receptor or binding site on a tumor vasculature endothelial cell or on a cancer cell;
administering the composition comprising the protein-carbon nanotube complex to the patient wherein the protein-carbon nanotube complex preferentially binds via the binding protein or peptide to the external receptor or binding site on an outer surface of the endothelial cell of the tumor vasculature of the cancer tumor or on an outer surface of the cancer cell in the patient; and
exposing the patient to electromagnetic radiation comprising a wavelength absorbable by the carbon nanotube causing elevation of the temperature of the carbon nanotube of the protein-carbon nanotube complex to a temperature which induces damage or death of the endothelial cell of the tumor vasculature or of the cancer cell to which the protein-carbon nanotube complex is bound.
[Snip from Description]
[0023]After treatment with the protein-SWNT complex or peptide-SWNT complex of the present invention, the tumor having the SWNTs bound thereto is then selectively exposed to electromagnetic radiation, for example, near-infrared (NIR) radiation. NIR radiation causes excessive local heating of SWNTs but does not otherwise affect biological systems which are not associated to the SWNTs (12). This excessive local heating of the SWNTs bound to the surface of endothelial cells of the tumor vasculature or to surfaces of the cancer cells leads to the destruction of the tumor vasculature or of the cancer cells and thus to the death or inhibition of growth of the tumor or cancer cells. Without wishing to be held to theory, it is believed that the killing of the tumor is by a combination of heating and cutting off the tumor's blood supply. In order to avoid damage to normal blood vessels, it is advantageous to delay the NIR treatment (or treatment with other wavelengths) until there is clearing of free SWNTs from the bloodstream such that substantially the only SWNTs in the body are those bound to the tumor vasculature or cancerous cells. The free SWNTs should clear within a matter of hours after administration. For example, in a recent study (30) with rabbits, SWNTs were injected into the bloodstream, and the SWNT concentration decreased exponentially with a half-life of 1.0.+-.0.1 hour. No adverse effects from low-level SWNT exposure could be detected from behavior or pathological examination.
Source
Note:
No --administering to the patient an immunostimulant to enhance the patient's immune response to antigens released from the cancer cells or tumor vasculature endothelial cells-- in this application. (See United States Patent Application 20090062785 below, for that.)
PAIR (to follow the USPTO prosecution history) - After the entry page - Insert '20080227687' in the box and select 'Publication Number'.
COMPOSITIONS AND METHODS FOR CANCER TREATMENT USING TARGETED SINGLE-WALLED CARBON NANOTUBES
| United States Patent Application | 20090062785 |
| Kind Code | A1 |
| Harrison, JR.; Roger G. ; et al. | March 5, 2009 |
The present invention is a method for detecting and destroying cancer tumors. The method is based on the concept of associating a linking protein or linking peptide such as, but not limited to, annexin V or other annexins to single-walled carbon nanotubes (SWNT) to form a protein-SWNT complex. Said linking protein or peptide can selectively bind to cancerous cells, especially tumor vasculature endothelial cells, rather than to healthy ones by binding to cancer-specific external receptors such as anionic phospholipids including phosphatidylserine expressed on the outer surfaces of cancer cells only. Irradiation of bound SWNTs with one or more specific electromagnetic wavelengths is then used to detect and destroy those cells to which the SWNTs are bound via the linking protein or peptide thereby destroying the tumor or cancer cells and preferably an immunostimulant is provided to the patient to enhance the immune response against antigens released from the tumor or cancer cells.
| Inventors: | Harrison, JR.; Roger G.; (Norman, OK) ; Resasco; Daniel E.; (Norman, OK) |
administering the composition comprising the protein-carbon nanotube complex to the patient wherein the protein-carbon nanotube complex preferentially binds via the binding protein or peptide to the external receptor or binding site on an outer surface of the endothelial cell of the tumor vasculature of the cancer tumor or on an outer surface of the cancer cell in the patient;
exposing the patient to electromagnetic radiation comprising a wavelength absorbable by the carbon nanotube causing elevation of the temperature of the carbon nanotube of the protein-carbon nanotube complex to a temperature which induces damage or death of the endothelial cell of the tumor vasculature or of the cancer cell to which the protein-carbon nanotube complex is bound; and
administering to the patient an immunostimulant to enhance the patient's immune response to antigens released from the cancer cells or tumor vasculature endothelial cells.
[Snip from Description]
[0027]After treatment with the protein-SWNT complex or peptide-SWNT complex of the present invention, the tumor having the SWNTs bound thereto is then selectively exposed to electromagnetic radiation, for example, radio frequency radiation, near-infrared (NIR) radiation, visible light, or UV radiation. The energy level of NIR radiation can be adjusted to give excessive local heating of SWNTs but not otherwise affect biological systems which are not associated to the SWNTs (12). This excessive local heating of the SWNTs bound to the surface of endothelial cells of the tumor vasculature or to surfaces of the cancer cells leads to the destruction of the tumor vasculature or of the cancer cells and thus to the death or inhibition of growth of the tumor or cancer cells. Without wishing to be held to theory, it is believed that the killing of the tumor is by a combination of heating and cutting off the tumor's blood supply. In order to avoid damage to normal blood vessels, it is advantageous to delay the NIR treatment (or treatment with other wavelengths) until there is clearing of free SWNTs from the bloodstream such that substantially the only SWNTs in the body are those bound to the tumor vasculature or cancerous cells. The free SWNTs should clear within a matter of hours after administration. For example, in a recent study (30) with rabbits, SWNTs were injected into the bloodstream, and the SWNT concentration decreased exponentially with a half-life of 1.0.+-.0.1 hour. No adverse effects from low-level SWNT exposure could be detected from behavior or pathological examination.
Source
Notes:
Resasco; Daniel E. is Chief Scientist and Founder of SouthWest NanoTechnologies, Inc. (SWeNT)
IP for Harrison; Roger G
US Patent filings
US Patents