**6.10 Hematological malignancies**

Hematological malignancies originate from the bone marrow or blood and result from the acquisition of genetic abnormalities that lead to unrestrained proliferation, resistance to cell death, and evasion of the immune system [214]. The occurrences of hematological malignancies, including leukemia, multiple myeloma, lymphoma, myelodysplastic syndromes, and myeloproliferative neoplasm, continuously increase despite recent advances which increased the five-year rate in many types of hematological malignancies [215]. Photodynamic therapy (PDT) has advantages over conventional anticancer therapy, including no risk of drug resistance and controllable ROS generation by controlled dosimetry [216–218]. TiO2 NPs have been used in many cancer types [40, 42, 219–221], but the biggest hurdle is the high energy band gap of TiO2 (anatase, 3.2 EV) which needs the excitation by detrimental UV

radiations. Doping of TiO2 with metal/non-metals resolves this issue by making TiO2 able to activate by absorbing light of longer wavelengths [222–224]. N-TiO2 exhibits anticancer activity and higher capability of ROS production in comparison to TiO2 NPs [39, 225, 226]. N-TiO2 was used as a photosensitizer in PDT for leukemia cells. Upon activation with visible light, N-TiO2 photosensitizers induced ROS-mediated autophagy in leukemia cells (K562), which increased with the increasing doses of light and photosensitizer. In addition, low doses of PDT also showed enhanced ROS and autophagy in normal peripheral lymphocytes. However, the typical human cell model showed no cytotoxic or inhibitory effects [41].

Acute lymphoblastic leukemia occurs due to the abnormal growth of white blood cells in the bone marrow [227, 228]. It is the most common cancer in children 2–5 years of age [229]. The treatment advancements show 90% effectiveness in curing the disease, but relapse and drug resistance remain the most significant clinical challenge [230]. Recently, using nanostructured devices and nanomaterials to deliver medications against cancer is the most advanced method for treating cancer [231]. Metal nanocomposites are being investigated for theranostics, and various functional groups are being incorporated to modify metal/metal oxide nanocomposites [232]. Recently, ZnO-TiO2-chitosan-amygdalin nanoparticles have gained much interest as potent anticancer agents. MOLT-4 (T-lymphoblast malignant cells) were treated with nanocomposite (ZnO-TiO2-chitosan-amygdalin) to evaluate its cytotoxic effect on these cells. The results showed increased cytotoxicity, mitochondrial membrane depolarization, caspase activation, and ROS generation in leukemia cells [233].

## **6.11 Oral cancer**

Oral Squamous Cell Carcinoma (OSCC) is characterized by local hypoxia and tumoral necrosis spreading on a large area, which is the cause of drug resistance and low chemotherapeutic response [234]. Immune suppression is also a factor that limits the therapeutic response and poor prognosis [235]. The primary therapy is surgical resection for OSCC, while radiotherapy and chemotherapy are additional treatment options [236]. However, with all the present treatment options, the five-year survival rate is still 60%, which severely damages the life quality [237]. Photodynamic theory utilizing nanoparticles as photosensitizers has gained much attention for OSCC cure and prevention [238, 239]. TiO2 NPs have widely investigated nanoparticles as photosensitizers in photodynamic therapy since their photocatalytic activity was discovered in 1972 [240–242]. Metal polypoidal complexes have attracted scientists as photosensitizers. Ru(II) complex TLD-1433 photosensitizers have been used in clinical trials for bladder cancer (non-muscle invasive bladder cancer) in Canada [243, 244]. TLD-1433 can potentially cause DNA damage under hypoxic conditions [243, 245]. Based on this phenomenon, TiO2@Ru@siRNA nanocomposite comprised SiRNA-loaded TiO2 NPs modified with ruthenium-based photosensitizers. This nanocomposite shows photodynamic effects upon irradiation with visible light. It can cause lysosomal damage, HIF-1α gene silencing, production of type I and type II ROS, and eradication of OSCC cells efficiently. In addition, it also reduces the expression of immunosuppressive factors and elevates the antitumor immune response. The PDX and oral rat carcinoma model significantly improved antitumor immunity and inhibited tumor progression and growth [246]. Pure TiO2 and TiO2 nanoparticles modified with ginger, garlic, and turmeric were used for anticancer activity against KB oral cell line by Maheshwari et al. They found that modified TiO2 showed better anticancer activity against oral cancer cells than pure TiO2 [247].

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