TiO2 Nanoparticles in Cancer Therapy as Nanocarriers in Paclitaxel's Delivery and Nanosensitizers in Phototherapies and/or Sonodynamic Therapy.

Nanomaterials have been offering improvements in different areas due to their unique characteristics, but cytotoxicity associated with their use is still a topic that concerns researchers. Causing cell death, at first glance, may seem to be a problem and the studies regarding signaling pathways involved in this toxicity are still in their infancy. However, there are scenarios in which this feature is desirable, such as in cancer treatment. Anti-cancer therapies aim to eliminate the cells of malignant tumors as selectively as possible. From this perspective, titanium dioxide (TiO2) nanoparticles (NPs) deserve to be highlighted as important and efficient tools. Besides being able to induce cell death, these NPs can also be used to deliver anti-cancer therapeutics. These drugs can originate from natural sources, such as paclitaxel (an antitumoral molecule derived from a vegetal source). The present review aims to explore the recent knowledge of TiO2 NPs as nanocarriers (promoting the nanodelivery of paclitaxel) and as nanosensitizers to be used in phototherapies and/or sonodynamic therapy aiming to treat cancer. Signaling pathways triggered by this nanomaterial inside cells leading to apoptosis (a desirable fate when targeting tumor cells) and challenges related to the clinical translation of these NPs will also receive attention in the future.

Review of Therapies using TiO2 Nanomaterials for Increased Anticancer Capability.

Recently, Titanium dioxide (TiO2) has been studied as an alternative to treat cancer diseases under different activation therapies. The aim of this review was to describe the effect of TiO2 nanoparticles (NPs) on some cancer cell lines and their interaction with phototherapies such as photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), and ultraviolet therapy (UV) for anticancer treatment. The use of TiO2 combined with PDT, PTT, SDT, or UV has shown a remarkable capacity to enhance the killing of cancer cells through reactive oxygen species formation. Thus, the combination of TiO2 and activation therapies exhibited great potential and could be a viable anticancer treatment strategy. However, more studies on phototherapies in combination with TiO2 and their effects under different experimental conditions (TiO2 concentration, type of cancer cells, and intensity and frequency of therapies) are necessary to guarantee the safe use of this kind of therapy.

Bifunctional Therapeutic Application of Low-Frequency Ultrasound Associated with Zinc Phthalocyanine-Loaded Micelles.

PURPOSE: Sonodynamic therapy (SDT) is a new therapeutic modality for the noninvasive cancer treatment based on the association of ultrasound and sonosensitizer drugs. Topical SDT requires the development of delivery systems to properly transport the sonosensitizer, such as zinc phthalocyanine (ZnPc), to the skin. In addition, the delivery system itself can participate in sonodynamic events and influence the therapeutic response. This study aimed to develop ZnPc-loaded micelle to evaluate its potential as a topical delivery system and as a cavitational agent for low-frequency ultrasound (LFU) application with the dual purpose of promoting ZnPc skin penetration and generating reactive oxygen species (ROS) for SDT. METHODS: ZnPc-loaded micelles were developed by the thin-film hydration method and optimized using the Quality by Design approach. Micelles' influence on LFU-induced cavitation activity was measured by potassium iodide dosimeter and aluminum foil pits experiments. In vitro skin penetration of ZnPc was assessed after pretreatment of the skin with LFU and simultaneous LFU treatment using ZnPc-loaded micelles as coupling media followed by 6 h of passive permeation of ZnPc-loaded micelles. The singlet oxygen generation by LFU irradiation of the micelles was evaluated using two different hydrophilic probes. The lipid peroxidation of the skin was estimated using the malondialdehyde assay after skin treatment with simultaneous LFU using ZnPc-loaded micelles. The viability of the B16F10 melanoma cell line was evaluated using resazurin after treatment with different concentrations of ZnPc-loaded micelles irradiated or not with LFU. RESULTS: The micelles increased the solubility of ZnPc and augmented the LFU-induced cavitation activity in two times compared to water. After 6 h ZnPc-loaded micelles skin permeation, simultaneous LFU treatment increased the amount of ZnPc in the dermis by more than 40 times, when compared to non-LFU-mediated treatment, and by almost 5 times, when compared to LFU pretreatment protocol. The LFU irradiation of micelles induced the generation of singlet oxygen, and the lipoperoxidation of the skin treated with the simultaneous LFU was enhanced in three times in comparison to the non-LFU-treated skin. A significant reduction in cell viability following treatment with ZnPc-loaded micelles and LFU was observed compared to blank micelles and non-LFU-treated control groups. CONCLUSION: LFU-irradiated mice can be a potential approach to skin cancer treatment by combining the functions of increasing drug penetration and ROS generation required for SDT.

Study of THP-1 Macrophage Viability after Sonodynamic Therapy Using Methyl Ester of 5-Aminolevulinic Acid Gold Nanoparticles.

Sonodynamic therapy (SDT) is emerging as new atherosclerosis treatment. The use of gold nanoparticles (AuNPs) as the vehicle for a sensitizer delivery improves reactive oxygen species formation. In this study, methyl ester of aminolevulinic acid (MALA) gold nanoparticles (MALA:AuNPs) functionalized with polyethylene glycol (PEG) were synthesized by photoreduction and characterized by ultraviolet/visible optical absorption, zeta potential and electron microscopy. The reactive oxygen species generation induced by ultrasound irradiation of MALA:AuNPs solutions was studied by observing the decrease in the 1,3-diphenylisobenzofuran emission band. The potential use of MALA:AuNPs as sensitizer for sonodynamic therapy was investigated on THP-1 macrophages. The cytotoxicity test was also described. The findings suggested that ultrasound combined with MALA:AuNPs provides impressive results in in vitro studies. Sonodynamic therapy with MALA:AuNPs through 2 minutes of ultrasound exposure (1 MHz and 1 W/cm2) culminated with total macrophage reduction. Thus, sonodynamic therapy combined with MALA:AuNPs has potential as a treatment for atherosclerosis.

Antimicrobial sonodynamic and photodynamic therapies against Candida albicans.

Candida albicans biofilms exhibit unique characteristics and are highly resistant to antifungal agents. Antimicrobial photodynamic therapy (aPDT) is an alternative treatment limited to treating superficial infections due to the poor light penetration. In this manuscript, the antifungal properties of sonodynamic therapy (SDT) were assessed. SDT uses ultrasound instead of light, enabling the treatment of deeper infections. Planktonic cells and biofilms of C. albicans were treated with aPDT or SDT, in addition to combined aPDT/SDT, with cell survival determined using colony forming units. The total biomass and structural integrity of the biofilms were also investigated. The results demonstrated that while individual aPDT or SDT eradicated suspensions, they had little impact on biofilms. However, combined aPDT/SDT significantly reduced the viability and total biomass of biofilms. Microscopic images revealed that biofilms treated with aPDT/SDT were thinner and comprised mainly of dead cells. These results highlight the potential of combined aPDT/SDT for the inactivation of C. albicans biofilms.