NANOTECHNOLOGY/PHOTODYNAMIC THERAPY: New strategy uses FDA-approved PDT to destroy deep-set tumors

A new type of nanoparticle, in combination with an FDA-approved photodynamic therapy (PDT), has been shown to effectively kill deep-set cancer cells in vivo with minimal damage to surrounding tissue—and fewer side effects than chemotherapy.1 "We have been able to do this with biocompatible low-power, deep-tissue-penetrating 980-nm near-infrared light," said Gang Han, Ph.D., assistant professor of biochemistry and molecular pharmacology at the University of Massachusetts Medical School (Worcester, MA), who led an international research team in the work. According to Yong Zhang, Ph.D., chair professor of National University of Singapore and an expert in the field who was not involved in the study, the team has created the deepest-ever PDT using an FDA-approved drug.

In PDT, the patient is given a non-toxic, light-sensitive drug that is absorbed by all the body's cells, including the cancerous ones. Light specifically tuned to the drug molecules are then selectively turned on the tumor area. The resulting interaction produces a highly reactive form of oxygen (singlet oxygen) that kills the malignant cancer cells while leaving most neighboring cells unharmed.

Current photodynamic therapies are only used for skin cancer or lesions in very shallow tissue. A paper reporting the novel strategy describes a new class of upconverting nanoparticles (UCNPs) that act as relay stations. The UCNPs are administered along with the photodynamic drug and convert deep-penetrating near-infrared (NIR) light into the visible red light needed to activate the drug.

To achieve this conversion, Han and colleagues engineered a UCNP to have better emissions in the red part of the spectrum by coating the nanoparticles with calcium fluoride and increasing the doping of the nanoparticles with ytterbium.

In their experiments, the researchers used the low-cost, FDA-approved photosensitizer drug aminolevulinic acid and combined it with augmented red-emission UCNPs they had developed. The researchers showed that the UCNPs successfully converted NIR light directed to tumors into red light, and activated the photodynamic drug at levels deeper than can be achieved currently with PDT. Performed both in vitro and with animal models, the combination therapy showed an improved destruction of the cancerous tumor using lower laser power.

1. A. Punjabi et al., ACS Nano, 28, 8, 10, 10621–10630 (2014); doi:10.1021/nn505051d.

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