**3. Metal-based nanomaterials in photodynamic application**

Nanomaterials usually refer to materials that possess at least one dimension in sizes ranging from 1 to 100 nm. They can be used alone as a PS or conjugated with PS and GEPS, in various types of PDT such as antimicrobial PDT and immune-PDT. Lipid PS nanoparticles (LPNs), polymer PS nanoparticles (PPNs), inorganic PS nanoparticles (IPNs), and self-assembled PS nanoparticles (SAPNs) are four groups of nanoparticles-based PSs in which IPNs are addressed in this review [18].

Due to the limitations of organic PSs, which include small stoke shift in porphyrin derivatives and low quantum yield due to aggregated form of porphyrin derivatives by steady p–p stacking in concentrated solutions, high toxicity, non-selectivity for tumor, and poor light absorption such as suboptimal tumor selectivity and poor light penetration into the tumor in second-generation PS, the interest of metal-based nanomaterial for PDT has been growing. Metal-based nanomaterials have been utilized as PSs and delivery vehicles because of properties that include: (1) relatively narrow size of metal nanoparticles, which can affect circulation time in the bloodstream and accumulation rate in tumors. Longer circulation time could be observed in therapeutic nanoparticles with a size of lower than 100 nm and higher accumulation in therapeutic nanoparticles with 20–200 nm size. (2) Shape distribution of metal nanoparticles that play a critical role in their internalization into the targeted cell. (3) Metal nanoparticles show surface plasmon resonance (SPR), which is associated with the surface plasmon resonance of the nanoparticles with a size smaller than the resonant absorption wavelength, used in PTT. According to this, the light wavelength used in PDT should be longer than the wavelength range of surface plasmon resonance. (4) Stability in water dispersion and long-term activity [11, 12, 19]. (5) Lower

PS leaching and higher loading efficiency of PSs. (6) High ability to interact with many compounds and generate both active and passive PS adsorption via the EPR effect [20]. Integration of PSs to nanoparticles is done via electrostatic or covalent interactions [21]. Subsequently, we discuss about various metal-based nanomaterials such as copper, O2 self-enriched metal-based nanoplatforms, transition metal oxides (TMOs), and transition metal dichalcogenides (TMD), upconversion (UCNPs) and metal organic frameworks. After that, we concentrate on photodynamic therapy based on gold and silver nanomaterials.

**Copper** ions have a vital role in biosystems including proliferation and differentiation of cells, promoting angiogenesis by stabilizing the expression of hypoxia-inducible factor (HIF-1α) and secretion of vascular endothelial growth factor (VEGF), cell migration, accelerating wound healing by collagen deposition, keeping the immune system functioning in such a way that copper ion deficiency causes immunodeficiency through reducing the phagocytic activity of granulocytes and the immunoglobulins synthesis, copper-composed nanomaterials have biomedical applications including antibacterial applications such as anti-multidrug-resistant bacteria and Cu-based enzymes, drug delivery, bioimaging, bioeffect and biosafety, catalytic nanotherapeutics, and nanotherapy. Due to photonic properties, Cu-based nanomaterials are used in PTT and PDT [12, 22]. In 2020, tumor microenvironment (TME) stimuli-responsive theranostic nanoplatform via assembling PS (chlorine e6, Ce6) modified carbon-dots (CDs-Ce6) and Cu2 + is designed. The existence Cu2 + in this nanoplatform creates extra chemodynamic therapy (CDT) via • OH generation through reaction with endogenous H2O2. Also, it enhances therapeutic efficiency by supernormal intracellular glutathione (GSH) depletion via a redox reaction This nanoplatform shows important features of FL imaging, synergistic treatment by PTT, PDT, and CDT [23].

**Metal–organic frameworks (MOFs)** are a kind of coordination polymers, which are usually composed of a metal oxide center and organic linkers. MOFs formed by self-assembly of metal ions clusters and organic ligands through the coordination bonds. MOFs have shown characteristics such as tunable sizes/shapes, high porosity, versatility, intrinsic biodegradability, well-defined biocompatibility, designable and ease of synthesis, and great drug delivery. They are multifunctional composites that enhance the PDT effect with other therapeutic modalities synergistically. PS molecules incorporate in MOF pores, therefore self-quenching and aggregation of PS molecules don't occur, and the distribution of ROS throughout the porous and rigid structure of MOF is easily accomplished [12, 24–27]. Nanoscale metal–organic frameworks (nMOFs) have potential characteristics, which lead to great biomedical applications. These properties include synthetic tunability in structures and compositions of nMOFs, high molecular payloads without self-quenching in photosensitizers, and facilitated diffusion of ROS through nMOFs pores to enhance the efficacy of PDT, radiotherapy (RT), radiotherapy-radiodynamic therapy (RT-RDT), and CDT, also reduce the adverse effect of hypoxia in aggressive tumors, which is based on evidence, hypoxia-inducible factor 1 (HIF-1) pathway activation triggers survival signaling in cancer cells. nMOFs could be used as immunoadjuvants, which leads to adaptive immunity boosting and PDT efficiency improvement. Passive and active targeting, regulation of singlet oxygen generation, innate biodegradability, prohibition of ROS neutralization, the capability of theranostic function, pH-responsive treatment of cancer [13, 26, 28, 29].

**Transition metal oxides (TMOs)** exhibit semiconductors such as properties including adjustable and different bandgaps, conductivity, absorption of light at

#### *Metal-Based Nanomaterials Photodynamic Action with a Focus on Au and Ag Nanomaterials DOI: http://dx.doi.org/10.5772/intechopen.109220*

certain wavelengths, various proportions of oxygen's and metals, consequently creating various structures, photocatalytic efficiency, and possible wide usage of them in the PDT/PTT fields. The process of photo-catalysis is as follows: photons with energy equal to or greater than the TMO bandgap energy cause the excitation of electrons from the valence band to the conduction band (CB) and create electronic holes. These electrons and created holes during redox reactions, and adsorption of molecules to the surface of TMOs causes the creation of free radicals such as hydrogen peroxide (H2O2), superoxide ion (O2 •−), and hydroxyl radicals (OH• ). ZnO, TiO2, MoO3, and WO3 are among the TMOs that have great photo-induced antibacterial activity. Doping metal ions in TMOs, which maintains charge balance due to the presence of oxygen vacancies, is one method for increasing photocatalytic activity. TMOs have improved photocatalytic efficiency. There can be polymorphism due to the possibility of their synthesis manipulation that nanofibers, nanorods, nanobelts, and nanowires are instances of their diverse forms [2]. For example, the tubular structure of TiO2 can perform as photocatalysis-propelled micro/nanomotors, and in an environment containing H2O2 (1%), O2 bubbles are produced due to the decomposition of H2O2. Titanium dioxide (TiO2), iron oxide, and cerium oxide are among the TMOs that can induce the lysosome-autophagy system through different pathways. TiO2 is one of the common TMOs that has attracted a lot of attention in biomedicine due to its low cost, chemical stability, and biocompatibility, including as PSs in PDT, anticancer, and surface coating, and substrates for stem cell expansion. TiO2 is usually an n-type semiconductor that has four polymorphisms. Anatase and rutile forms have efficient photocatalytic applications due to their broader band gap [14].

**Transition metal dichalcogenides (TMDs)** are semiconductors with stacking configurations and several structural phases. TMDs' structural phases are the coordination of the three atomic planes of transition metal (group IV, V, VI, VII, IX, or X) and two chalcogenides (S, Se, and Te). TMDs have bandgap energies within the range of 1.6–2.4 eV, which are suitable for visible light catalysis. TMDs act as co-catalysts and link to other photocatalysts. TMDs have electron sinks so they could retard photogenerated electron–hole recombination, which causes it widely used in photodynamic therapy and biosensing. Molybdenum disulfide (MoS2) is one of the TMDs with poor cytotoxicity and higher NIR absorption. MoS2 as a member of grapheneanalog materials has graphene-derived features such as superior surface-to-volume ratios and hydrophobic surface nature leading to absorbing biomolecules, hydrophobic drugs, and genes, so it could be a drug delivery vehicle. According to studies, MoS2 has PDT ability without adding other PSs. For example, MoS2 nanoflowers have high NIR absorption and peroxidase-like activity, leading to decomposition of a low concentration of H2O2 and hydroxyl radical generation. Also, MoS2 QDs could generate <sup>1</sup> O2 with radiation of 630 nm laser light [2, 30].

**Upconversion NPs (UCNPs) and quantum dots** are two major groups of transducing nanoparticles. The limited penetration depth of UV and visible light is a challenge for PDT, so transducing nanoparticles are a solution for this challenge so that they could transfer energy with wavelength out of PSs' absorption range to conjugated PS molecules Quantum dots (QDs) as semiconductor nanocrystals are constructed of different elements such as silicon, cadmium, selenide, and graphene, and they have optical and emission properties – dependent size (1–10 nm). QDs with larger sizes after that are excited by a specific wavelength of light, emitting light with low energy in the red spectrum range while the emission wavelength of smaller QDs is in the blue spectrum range. QDs could generate ROS by transferring energy to triplet oxygen, but their <sup>1</sup> O2 yield is low so it is necessary to design QDs conjugated with PSs

that have enhanced energy transfer for increasing 1 O2 yield [2, 15]. Other groups of nano-transducer are UCNPs, constructed of a crystalline host lattice that may possess transition metals, lanthanide, or actinide ions, such as ytterbium (Yb3+), erbium (Er3+), and thulium (Tm3+) [15, 31]. UCNPs provide anti-stoke luminescent because they could generate short-wavelength light (visible or UV light) from short-wavelength incident light (NIR). Up-conversion luminescence (UCL) efficiency depends on dopant ion ratio and up-conversion luminescence mechanisms.

Excited state absorption (ESA), photon avalanche (PA), and energy transfer up-conversion (ETU) are three main mechanisms that are observed in UCNPs either alone or in combination, for a luminescent generation. Energy transfer is the dominant mechanism that is existence in UCNPs such as NaYF4 doped with Yb3+ (sensitizer), Er3+, or Tm3+ (activator). ETU mechanism occurs in a two-ion-involved system, in which one of them donates energy is named sensitizer (S) ion and the other is activator (A) with the ability of visible or UV light emission. Each of the two neighboring ions absorbs the same energy, when the excited state of S and A is near enough, non-radiative energy transferring occurs from S to A, then the activator is excited to the upper energy state and emits higher-energy photons, while sensitizer comes back to ground state [2, 31, 32]. UCNPs could act as PSs, drug delivery systems, and bioconjugated, so they have wide applications in PDT including deep tumors PDT, antimicrobial PDT, and the PDT of viral infections. UCNPs such as lanthanidesdoped platforms could incorporate into the design of MOF-based hybrid nanomaterials and act as a wavelength-shifting platform to broaden the light-harvesting properties of MOFs, which could absorb NIR light [2, 31, 33].
