ROS-Mediated Photodynamic Cancer Therapy by Nanoparticle-Juniper publishers

  Global Journal of Nanomedicine-Juniper publishers

Introduction

Traditional cancer treatment technologies such as chemotherapy and surgery have some limitations, including poor patient compliance and adverse drug reaction [1]. In recent years, photodynamic therapy (PDT) has received extensive attention for cancer treatment in the presence of photosensitizer and molecular oxygen due to its minimal invasiveness, nondrug resistance, low poison, and accurate tumor therapy [1-3]. PDT depends on the photochemical reaction between light and the photosensitizer to produce reactive oxygen species (ROS) that eventually leading to cancer cell death [4,5]. Since metal-based nanoparticles (NPs) are biocompatible, they are promising materials that can be used as photosensitizer for PDT [6,7]. It has been demonstrated that metal oxide or metallic NPs exposed to light can produce ROS that induce cancer cell damage [7,8]. In this review, we will summary the therapeutic mechanism of metal-based NPs toward cancer cells, influence factors of ROS production, and ROS production mechanism of metal-based NPs.

Therapeutic mechanism of metal-based nanoparticles

The main therapeutic mechanism of metal-based NPs to cancer cells is associated with the production of ROS andsubsequent ROS-induced apoptosis in cancer cells [7,8]. Three types of ROS (hydroxyl radical (•OH), singlet oxygen (1O2) and superoxide radical (O2•−) jointly contribute to the death of tumor cells [9]. Among them, •OH has the ability to non-specifically oxidize many any types of macromolecules, such as nucleic acids, carbohydrates, and DNA [8]. 1O2 is the most detrimental ROS to tumor cells because it reacts extensively with amine acids, proteins unsaturated fatty acids and steroids [8]. This can lead to oxidation and degradation of bio membrane in cancer cells. O2•− reacts with macromolecules slowly. However, O2•− can produce hydrogen peroxide (H2O2) by disproportionate reaction [9]. H2O2 can be converted to •OH and 1O2. Consequently,1O2, •OH and O2•− may coexist and contribute to cancer therapy by NPs.

Effect factors of ROS production by metal-based nanoparticle

ROS production of metal-based NPs could be influenced by many factors, such as physicochemical properties of NPs (e.g. particle size and surface coating), solution chemistry (e.g. aqueous media), and environmental conditions (e.g. dissolved organic matter (DOM) and light conditions) [8,10]. The role of these parameters in ROS production is discussed below.

Effect of particle size

In general, when the particle size reduces, ROS production concentrations increase due to the larger surface areas and more reactive sites of NPs [11]. Previous study has shown that ROS production by Au (5-250 nm) under UV or X-ray irradiation linearly increased with the decrease of NPs diameters [6]. Metaloxide NPs have been found to produce more ROS than their bulk counterparts because larger surface areas of NPs provide more reaction sites for light absorption and oxygen exposure [8].

Effect of surface coating

Surface coating can change the light absorption characteristics of metal-based NPs and will eventually affect their ROS production profile. In the field of biomedicine, surface coating was decorated on the metal-based NP surface to enhance ROS generation for photodynamic treatment of cancer [12]. However, Wang et al. demonstrated that ginger and mint decreased ROS production by Ag NPs in cells of Hep G2 and He La [7]. This is mainly because biocapping agents on the surface of Ag NPs have antioxidant activity [8].

Effect of aqueous medium

The ability of ROS production by metal-based NPs is significantly impacted by the physicochemical properties of the aqueous medium [13,14]. Previous studies have found that ZnO NPs generated O2•−, •OH and 1O2 in deionized water, sodium chloride solution, phosphate-buffered saline and minimal Davis medium, but only formed 1O2 and O2•− in Luria-Bertani medium [14]. ROS production ability could be decreased by the organic components (e.g., yeast extract glucose, tryptone and citrate) in the aqueous media [14].

Effect of DOM

No consistent conclusions on the role of DOM in ROS production by metal-based NPs exist. For example, researchers have shown that intracellular ROS production by TiO2 NPs was promoted by humic acid (HA) in aquatic environment under natural sunlight irradiation. However, Lin et al. have demonstrated that HA inhibited ROS production by TiO2 NPs under natural sunlight irradiation, which was mainly because HA acted as ROS quenchers [15]. The metal ions released by metal-based NPs could disable the triplet states of HA, resulting in their reduced sensitization ability for ROS production [16]. Moreover, DOM may serve as a UV filter and finally reduced ROS generation by NPs [17].

Effect of light condition

Light exposure plays an important role in ROS production of metal-based NPs in natural condition [14,18,19]. Previous studies have shown that light exposure, such as irradiation by xenon lamp, UV lamp, X-ray, and solar, could enhance ROS production by metal-based NPs [14,18,19]. 1O2, •OH and O2•−cannot be detected by all metal-oxide and metallic NPs in the dark, but at least one type of ROS was detected when exposed to UV light. This was because the light irradiation induces surface plasmon resonance (SPR) production in the surface of metallic NPs and electron-hole pairs in metal-oxide NPs, which will be elucidated in the following section.

Production mechanism of ROS

The generation mechanism of ROS in metal-oxide NP suspensions was clarified by comparing the band edge energy levels of metal oxides with the redox potentials of various ROS production [20,21]. For example, the Ec value of TiO2 is -0.28 eV relative to normal hydrogen electrodes (NHE; all Ec and Ev values are relative to NHE) [22], which is lower than -0.2 eV (EH of O2/O2•−). This demonstrate that the electrons in TiO2 NPs have enough reductive power to reduce O2 and result in O2•− production. The reductive ability of the electrons in CuO conduction band (Ec value of 0.69 eV) is not enough to reduce O2 [22], thus no measurable amount of O2•− was detected in CuO suspension.

Metallic NPs can interact with light by scattering or absorbing the photons [6,18]. When excited by light, the oscillating electric field of the incoming radiation leads to coherent collective oscillation of the free mobile electrons on the surface of metallic NPs [6,18]. When the frequency of surface electron oscillation equals to that of the photon, SPR is produced [6,18]. A strong absorption of incident photon energy is induced by SPR, which can be transferred to O2 and result in 1O2 production [6,12]. The photoelectrons transferred to O2 are responsible for the production of O2•− [6], which can further enhance •OH production under light irradiation [6,12]. Research has showed that Ag NPs generated O2•− and •OH [23]. 1O2 was not discovered, which was primarily due to the consumption of 1O2 by the released Ag+ [23].

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