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Photodynamic therapy is a therapeutic option to treat cancer and other diseases. PDT is used every day in dermatology, and recent developments in the treatment of glioblastoma, mesothelioma or prostate have demonstrated the efficacy of this modality. In order to improve the efficacy of PDT, different strategies are under development, such as the use of targeted PS or nanoparticles to improve selectivity and the design of light devices to better monitor the light dose. Due to the low penetration of light into tissue, another way to improve the efficacy of PDT to treat deep tumors is the use of upconversion NPs or bi-photon absorption compounds. These compounds can be excited in the red part of the spectrum. A relatively new approach, which we will call PDTX, is the use of X-rays instead of UV-visible light for deeper penetration into tissue. The principle of this technique will be described, and the state-of-art literature concerning this modality will be discussed. First, we will focus on various photosensitizers that have been used in combination with X-ray irradiation. To improve the efficacy of this modality, nanoparticles have been designed that allow the conversion of high-energy ionizing radiation into UV-visible light; these are potential candidates for the PDTX approach. They will be discussed at the end of this review.

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Photodynamic therapy (PDT) is a well-established technique employed to treat aged macular degeneration and certain types of cancer, or to kill microbes by using a photoactivatable molecule (a photosensitizer, PS) combined with light of an appropriate wavelength and oxygen. Many PSs are used against cancer but none of them are highly specific. Moreover, most are hydrophobic, so are poorly soluble in aqueous media. To improve both the transportation of the compounds and the selectivity of the treatment, nanoparticles (NPs) have been designed. Thanks to their small size, these can accumulate in a tumor because of the well-known enhanced permeability effect. By changing the composition of the nanoparticles it is also possible to achieve other goals, such as (1) targeting receptors that are over-expressed on tumoral cells or neovessels, (2) making them able to absorb two photons (upconversion or biphoton), and (3) improving singlet oxygen generation by the surface plasmon resonance effect (gold nanoparticles). In this chapter we describe recent developments with inorganic NPs in the PDT domain. Pertinent examples selected from the literature are used to illustrate advances in the field. We do not consider either polymeric nanoparticles or quantum dots, as these are developed in other chapters.

Nanoparticles (NPs) have been shown to have good ability to improve the targeting and delivery of therapeutics. In the field of photodynamic therapy (PDT), this targeting advantage of NPs could help ensure drug delivery at specific sites. Among the commonly reported NPs for PDT applications, NPs from zinc oxide, titanium dioxide, and fullerene are commonly reported. In addition, graphene has also been reported to be used as NPs albeit being relatively new to this field. In this context, the present review is organized by these different NPs and contains numerous research works related to PDT applications. The effectiveness of these NPs for PDT is discussed in detail by collecting all essential information described in the literature. The information thus assembled could be useful in designing new NPs specific for PDT and/or PTT applications in the future.

Salinomycin (1) exhibits a large spectrum of biological activities including the capacity to selectively eradicate cancer stem cells (CSC), making it and its derivatives promising candidates for the development of drug leads against CSC. It has been previously shown that salinomycin and its C20‐propargylamine derivative (Ironomycin (2)) accumulate in lysosomes and sequester iron in this organelle. Herein, a library of salinomycin derivatives is reported, including products of C20‐amination, C1‐esterification, C9‐oxidation, and C28‐dehydration. The biological activity of these compounds is evaluated against transformed human mammary epithelial HMLER CD24low/CD44high cells, a well‐established model of breast CSC, and HMLER CD24high/CD44low cells deprived of CSC properties. Unlike other structural alterations, derivative 4, which displays a cyclopropylamine at position C20, showed a strikingly low IC50 value of 23 nm against HMLER CD24low/CD44high cells. This study provides highly selective molecules to target the CSC niche, a potential interesting advance for drug development to prevent cancer resistance.

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Photodynamic therapy (PDT) is mainly used to destroy cancerous cells; it combines the action of three components: a photoactivatable molecule or photosensitizer (PS), the light of an appropriate wavelength, and naturally occurring molecular oxygen. After light excitation of the PS, the excited PS then reacts with molecular oxygen to produce reactive oxygen species (ROS), leading to cellular damage. One of the drawbacks of PSs is their lack of solubility in water and body tissue fluids, thereby causing low bioavailability, drug-delivery efficiency, therapeutic efficacy, and ROS production. To improve the water-solubility and/or drug delivery of PSs, using cyclodextrins (CDs) is an interesting strategy. This review describes the in vitro or/and in vivo use of natural and derived CDs to improve antitumoral PDT efficiency in aqueous media. To achieve these goals, three types of binding modes of PSs with CDs are developed: non-covalent CD–PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies. This review is divided into three parts: (1) non-covalent CD-PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies, (2) incorporating CD–PS systems into hybrid nanoparticles (NPs) using up-converting or other types of NPs, and (3) CDs with fullerenes as PSs.