Future Medicine

The photonic nanomedicine revolution:
Let the human side of nanotechnology emerge
Naomi J Halas

Department of Electrical & Computer Engineering & the Laboratory for Nanophotonics,
Rice University, 6100 Main St., Houston, TX 77005-1892, USA. halas@rice.edu

Nanoparticle-based photothermal ablation is showing extraordinary promise as an unusually effective and potentially revolutionary cancer therapy. This approach uses light at near-infrared wavelengths that pass through tissue, in combination with gold-based nanoparticles specifically engineered to absorb that light and convert it to heat. The light-absorbing nanoparticles serve as highly localized heat sources that destroy cells in their immediate vicinity by hyperthermia [4]. This method has been shown to be highly effective in extensive animal studies, with tumor remission rates above 90%. Extensive toxicity studies have been performed on nanoshells, the nanoparticles most utilized to date in these studies, and this is being followed by similar studies on other types of noble metal nanoparticles that are also promising candidates for this therapeutic modality. The US FDA has recently granted approval for initial human trials of this therapy for head and neck cancer. Given the extraordinary promise of these potentially revolutionary therapeutic nanodevices and their impending availability, research into nanoparticle-based therapeutics is beginning to move into the next critical phase: the development of nanoparticle-assisted therapeutic practices specifically for clinical use.
One of the most extraordinary aspects of nanoparticle-assisted photothermal therapy for tumor remission is that it is drug free: cell death is induced by the localized heat generated when the nanoparticles absorb near-infrared light. This is an exceedingly important aspect: with heat as the source of cell death, this approach is independent of the specifics of the immune systems of various animals on which it may be tested. This also means that with this therapeutic approach, the nanoparticles can be classified as a device, rather than a drug. They are nanoscale lenses, delivering highly focused light to cancer cells or within tumors much like a lens that captures sunlight delivers enough heat to a leaf to enable it to burst into flames. However, in the case of nanoparticle-based photothermal therapy, the heat required to induce cell death is only approximately 15–20? above physiological temperatures. Because the nanoparticles are devices and not drugs, operating only on heat and light and not interacting chemically with living systems, this therapy, and other variants of this approach, may be available for patients and practitioners in just a few years.
For cancer, this nanoparticle-based strategy will ultimately allow the clinician to remove localized tumors with a simple, minimally invasive, nonsurgical procedure performed, for example, with a portable laser in an outpatient clinic instead of a surgical suite. This could fundamentally revolutionize the treatment of virtually all soft-tissue cancers, transforming this feared, life-threatening disease to an actively managed illness that can be treated and contained prophylactically.
While early detection and treatment of localized, noninvasive tumors is ideal, in reality it is not the typical diagnostic scenario. In any given year, invasive carcinoma diagnoses far outnumber the diagnosed cases of localized cancer. While nanoparticle-based photothermal therapy appears to be highly promising for the removal of localized tumors, an important and immediate challenge is to develop strategies to address more advanced stages of cancer with this powerful new modality. The proliferation of cancer to the lymph nodes directly adjacent to the primary tumor is a key diagnostic for cancer clinicians, and determines the course of treatment. In conventional surgery, these adjacent lymph nodes are typically removed along with the primary tumor. Recent advances in the development of strongly enhanced fluorescent markers for deep-tissue imaging may make resolution at the limit of a few cells possible. Targeted imaging of cancer in lymph nodes, to quantify the proliferation of cancer beyond carcinoma in situ, could be combined with photothermal destruction of targeted cancer cells using nanoparticle-based probes. This would provide a method for removing the cancer cells in the lymph nodes while preserving, largely intact, the lymphatic system of the cancer patient. As markers become available this general approach should be extendable to additional strategies for the treatment of metastatic disease.
The centers of solid tumors are frequently observed to be largely necrotic, resulting from prolonged hypoxia: insufficient availability of oxygen and glucose to meet the metabolic demands of the malignant cells. Because of the decreased blood flow in these tumor regions, they are inaccessible by, and therefore highly resistant to, conventional chemotherapies. One possible scenario for the progression of cancer to its latter, highly fatal stages is that cells surviving in these inaccessible hypoxic regions may themselves be the source of subsequent local recurrence and distant metastasis. One of the body’s responses to the presence of a malignant neoplasm is to recruit peripheral blood monocytes into the tumor, which then differentiate into macrophages. These cells have been shown to promote metastatic disease. One potentially promising scenario is to induce uptake of nanoshells into monocytes, which are then recruited into the hypoxic regions of tumors: the presence of the nanoshells would then permit photothermal destruction of the necrotic region. This type of approach may provide a critical new strategy for thwarting tumor metastasis.
An exciting new use of nanoparticle-assisted photothermal therapy is in delivery methods for gene therapy. It is widely recognized that gene-based therapies hold extraordinary therapeutic promise for cancer: many genetic markers have been discovered, and numerous DNA-based therapeutics have been proposed for the targeting of pathogenic genes for various cancers. Genetic vaccines have also been suggested for certain forms of cancer now believed to have a hereditary basis, such as the 42–57% of prostate cancer cases that correlate with inherited genetic factors. However, while the discovery of gene targets and the development of gene-based therapies at the molecular level has been pursued aggressively for more than 15 years, the transition of these therapies from the research laboratory to the clinic is at a virtual impasse and fraught with severe challenges. Unprotected gene therapy drugs (DNA- or RNA-based) introduced into the bloodstream are rapidly broken down, preventing their diffusion to the region of disease. Viruses, the initial carrier of choice in most gene therapy research, present a variety of potential problems to the patient – toxicity, immune and inflammatory responses, and gene control and targeting issues. The first clinical gene therapy studies utilizing a viral delivery vector resulted in patient death, and had to be terminated in their initial stage. There is a clear critical need for nonviral delivery vectors for gene therapy for this field to advance towards its many clinical applications. Nanoparticle–biomolecule light-actuated complexes are being developed and tested with clinically relevant genetic markers. For example, by combining gold nanoparticles with specific oligonucleotides, the nanoparticle complex can serve as a nonviral gene-delivery vector, where incident light can trigger the release of the nucleotide once the complex has been taken up by cells. Initial release data in cell culture studies show that this approach has outstanding promise for gene delivery. Light-triggered nucleotide release from these nanoparticle–molecule complexes makes them particularly well suited for the localized administration of gene therapy drugs into the tissue or organ of interest.
In conclusion, nanoparticle-assisted, photothermal therapeutic strategies have the capability of providing revolutionary tools in many battles against human disease, with the clear potential for highly effective therapy for cancer and other diseases. Moreover, this approach is unparalleled in its level of noninvasiveness and in its low, essentially nonexistent toxicity. The long-term impact of the development of these new treatment methods will be to change the way we treat cancer. This approach may also provide effective new strategies for treatments of other, lesser known and less-studied diseases such as autoimmune disorders, where few or no treatment options currently exist. In addition to increased efficacy, an extraordinary advantage of nanoparticle-assisted photothermal therapy is that essentially no, or minimal, side effects are expected. Replacing current chemotherapy treatments, with their high level of systemic toxicity and deleterious side effects, with this benign therapeutic approach will greatly increase the quality of life for cancer patients and their families.
Financial & competing interests disclosure The author is the inventor of nanoshells and pioneered nanoparticle-based photothermal therapies along with her collaborators at Rice University (TX, USA), J West and R Drezek. She is the co-founder of Nanospectra Biosciences, Inc. (www.nanospectra.com), a Houston-based company dedicated to the translation of this therapeutic approach into clinical practice. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Source >http://www.futuremedicine.com/doi/full/10.2217/nnm.09.26