Nanomaterials for Enhanced Photodynamic Therapy

*Lucas F. de Freitas*

## **Abstract**

Photodynamic therapy is a non-invasive option for eliminating superficial tumors and to control infections. However, despite some protocols are already approved for the clinic, PDT applications could be much broader if some of its main hindrances were overcome. For instance, the most efficient photosensitizers are hydrophobic, so if one injects them intravenously they tend to aggregate and to be internalized by phagocytes in the blood, impairing the delivery to the target site. In addition, visible light has a limited penetration in tissues, therefore the main applications of PDT are limited to superficial tumors unless an invasive procedure is used for the light to reach deeper sites. Another setback is the hypoxia that commonly happens in tumors, hindering the full potential of PDT as it depends on a constant oxygen supply. In this chapter the reader will find some strategies based on Nanotechnology to overcome these and other obstacles for PDT to reach its full clinical potential, i.e. hypoxia-reverting protocols, X-ray-driven PDT, Cherenkov radiation-driven PDT, and active tumor-targeting.

**Keywords:** photodynamic therapy, nanotechnology, active targeting, X-PDT, CR-PDT

#### **1. Introduction**

Nanotechnology consists on the development of materials with dimensions usually between 1 and 100 nm, where the properties of matter are significantly different than their bulk counterparts, and can be tuned to the desired application. These novel chemical and physical properties are usually derived from quantum effects and from the drastically increased surface-to-volume ratio. Furthermore, since many biological structures, i.e. proteins, organelles, viruses, etc., can be found within the nanometric scale, synthetic nanostructures have easy access to biological systems.

Although Nanotechnology started purely as a physical and materials science, soon the medical properties of nanomaterials became evident, and the new era of nanomedicine and nanopharmacy started. Nanomaterials are now recognized as excellent therapeutic and diagnostic tools, and thousands of novel compounds and nanostructures are developed every year, for the most diverse applications.

As you will see in this chapter, Nanotechnology can help practitioners to overcome several hindrances of photodynamic therapy that have so far prevented this approach from reaching a broader clinical success. Over the last decade, nanostructures have been applied as drug delivery platforms for PDT, and as strategies to enhance the efficiency of photosensitizers in generating ROS upon irradiation.

The nanoparticles can be organic or inorganic, can assume a multitude of shapes and sizes within the nanoscale, can act as photosensitizers themselves or as energy transducers. Even further, nanocarriers prevent the complications that arise from the poor solubility of photosensitizers in aqueous media, and increase the tumor accumulation in order to preserve healthy tissues. We are going to discuss in details the most relevant data regarding the enhancement of PDT by the use of nanomaterials.
