**4. Photodynamic therapy**

Photodynamic Therapy (PDT) is an emerging non-invasive therapy that received clinical approval. This therapy is preferred over conventional anticancer treatments due to its high efficacy, specificity, and subtle side effects [1, 31]. This therapeutic strategy utilizes photosensitizers (chemicals, drugs) with light in the presence of molecular oxygen to stimulate the generation of ROS, thereby inducing tumor cell death. However, the combination of PDT and drug is expected to produce a more significant effect as an anticancer treatment since PDT alone is relatively inefficient in eradicating cancer [32–35]. The photosensitizer should ideally enter the target cells/ tissues without affecting the neighboring healthy tissues (**Figure 2**).

Moreover, the treatment can be confined to an elevated concentration of photosensitizers. This promising strategy can be applied to inhibit microbial growth and treat cancer and infectious diseases [35]. The effectiveness of PDT relies on the type of photosensitizers used. Several materials, including inorganic [33], organic, and porphyrin-based materials [34], have been used as photosensitizers in PDT. However, several drawbacks have been associated with these materials, such as inadequate dispersion in water and photostability. In addition, these materials cannot absorb light of longer wavelength, i.e., greater than 700 nm, which results in improper light penetration and subsequent reduction in cell killing effect. This causes unwanted toxicity and damage to cancer and normal cells or tissues.

*Nano Titania Applications in Cancer Theranostics DOI: http://dx.doi.org/10.5772/intechopen.111626*

**Figure 2.**

*TiO2 NPs-based photodynamic or sonodynamic therapy of cancer cells. The ROS generated after photosonoactivation results in mitochondria damage leading to cytochrome c release to induce apoptosis in cancer cells (developed by using BioRender).*

Metal oxide nanoparticles have been widely studied as photosensitizing agents in PDT due to the drawbacks associated with porphyrin-based photosensitizing agents. TiO2 NPs gained immense interest due to their distinct characteristics, enabling them to effectively kill tumor cells upon optical irradiation. Irradiation of TiO2 NPs, with an energy greater than or equal to the bandgap, causes the redox reaction on the surface of these NPs, which leads to the generation of reactive oxygen species, including superoxide anions, hydrogen peroxide, and hydroxyl radicals [36, 37]. TiO2 is more stable than other conventional photosensitizers because they are nanosized particle with anti-photodegradable stability. TiO2 NPs have been used as photosensitizers in several types of tumor cell lines, which include HepG2 (hepatocellular carcinoma cells) [38], HeLa (cervical cancer cells) [39], MDA-MB-468 and MCF7 (breast cancer cells) [40], leukemia cells (K592) [41], and lung cancer cells (NSCLC) [42].

TiO2 NPs are considered marvelous photosensitizers; however, their possible toxicity impedes their applicability in PDT [8, 43]. TiO2 can be excited in its pristine form by short-wavelength ultraviolet irradiation. Lagopati et al. conducted a study in which they used TiO2 as photosensitizers against breast cancer cells (MCF7 and MDA-MB-468). TiO2 nanostructures were prepared by using the sol-gel technique. The results showed significant effects of the applied modification against MDA-MB-468 cells [44]. Modifying TiO2 NPs with Quantum Dots (QDs) have received significant attention since they allow TiO2 to absorb light of much longer wavelengths and, thereby, deeper tissue penetration. In PDT, QDs usually possess dual-function properties and act as energy transducers and carriers for photosensitizers. Ramachandran et al. synthesized TiO2 NPs by microwave-assisted synthesis and TiO2 conjugated with N-doped graphene QDs (N-GQDs/TiO2) by two-pot hydrothermal method. N-GQDs/TiO2 nanocomposites generated ROS, particularly singlet oxygen, upon activation with the light of the near-infrared region. This induced cell death in MDA-MB-231 cells more significantly than in the HS27 cell line (human foreskin fibroblasts) [45].
