Turning Up the Heat: Development of Non-Toxic Photothermal Therapy Agents

Metastasis is one of the two fundamental properties of malignant tumors and is associated with poor patient outcomes. Indeed, approximately 90% of human cancer deaths are attributed to metastasis. Not surprisingly, metastatic cancer is considered one of the largest current challenges in cancer diagnosis and treatment. Advances in nanomedicine over the previous twenty years have led to the recent development of many novel approaches in anti-metastasis treatment. For a review of current approaches, the reader is encouraged to read, “Emerging nanomedicine approaches fighting tumor metastasis: animal models, metastasis-targeted drug delivery, phototherapy, and immunotherapy” http://pubs.rsc.org/en/content/articlepdf/2016/CS/C6CS00458J.

One of these current methods is the use of photothermal therapy (PTT). PTT uses near-infrared (NIR) absorbing particles, often nanoparticles, with a resonance peak in the 700-1200 nm range. Once delivered to the target site, the particles are subsequently activated by NIR light, where they convert the optical energy to heat resulting in ablation of the tumor cells.

Despite representing a promising candidate for cancer treatment, one of the major limitations in the adoption of PTT has been the toxicity and non-biodegradability of the nanoparticles themselves. Typically, PTT nanoparticles are constructed of various organic and inorganic agents. These can include carbon and gold nanoparticles, small organic dyes, and conjugated polymers. Thus, one of the major goals in PTT research is the development of photothermic agents that are non-toxic, exhibit prompt clearance rates, demonstrate extremely robust photostability, have strong NIR absorbance, and display excellent imaging capability to enable real-time tracking. The use of nanoscale metal-organic particles (NMOP) in biomedicine has previously been shown to exhibit great potential in biomedical imaging and cancer therapies.

A recent study lead by Yu Jang and colleagues at the State Key Laboratory of Quality Research in Chinese Research at the University of Macau, and in collaboration with researchers at Soochow University, China, reported the development of a new class of photothermal agent that demonstrates high biodegradability coupled with imaging capacity to allow real-time tracking. Yu Jang and colleagues developed a new type of NMOP that coupled real-time imaging with high biodegradability. They generated the NMOP by allowing self-assembly of Mn2+ ions with IR825, an NIR absorbing heptamethine indocyanine dye, to occur, resulting in production of the nanoparticle. The NMOP was subsequently mixed with dopamine to generate a PDA shell and then further coated with PEG-amine to produce Mn-IR825@PDA-PEG.

To test the properties of Mn-IR825@PDA-PEG Yu Jang et al. used the metastatic 4TI tumor-bearing mouse model. Twenty-four hours after injection with Mn-IR825@PDA-PEG the NMOPs were activated by irradiation at 808 nm, resulting in a rapid temperature rise of between 34 to 52 oC. They also reported that tumors were eliminated within 18 days of treatment without reoccurring and, furthermore, tumor bearing mice that received PTT treatment were still cancer free after 60 days post-treatment. In comparison, the average life span of control mice was less than 24 days. The authors also noted that mice receiving the NMOP PTT treatment displayed normal behavioral traits, had no loss of body mass, and did not have any organ damage. They also found that the NMOP was readily excreted in urine without bioaccumulation in organs, indicating that it is non-toxic.

While PTT has been examined for some time now as a potential cancer treatment, particularly for treatment of metastatic cancer, the potential toxicity of the PTT nanoparticles has proven a considerable limitation. However, this study has illustrated that it is possible to synthesize non-toxic PTT agents that still remain extremely effective in treating metastatic cancer in vivo.

Source: Y Yang, J Liu, C Liang, L Feng, T Fu, Z Dong, Y Chao, Y Li, G Lu, M, Chen, and Z Liu. (2016) Nanoscale Metal-Organic Particles with Rapid Clearance for Magnetic Resonance Imaging-Guided Photothermal Therapy. ACSnano. http://pubs.acs.org/doi/ipdf/10.1021/acsnano.5b07882

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