Recent Advances in Photodynamic Therapy: Metal-Based Nanoparticles as Tools to Improve Cancer Therapy

Abstract

Cancer remains a significant global health challenge, with traditional therapies like surgery, chemotherapy, and radiation often accompanied by systemic toxicity and damage to healthy tissues. Despite progress in treatment, these approaches have limitations such as non-specific targeting, systemic toxicity, and resistance development in cancer cells. In recent years, nanotechnology has emerged as a revolutionary frontier in cancer therapy, offering potential solutions to these challenges. Nanoparticles, due to their unique physical and chemical properties, can carry therapeutic payloads, navigate biological barriers, and selectively target cancer cells. Metal-based nanoparticles, in particular, offer unique properties suitable for various therapeutic applications. Recent advancements have focused on the integration of metal-based nanoparticles to enhance the efficacy and precision of photodynamic therapy. Integrating nanotechnology into cancer therapy represents a paradigm shift, enabling the development of strategies with enhanced specificity and reduced off-target effects. This review aims to provide a comprehensive understanding of the pivotal role of metal-based nanoparticles in photodynamic therapy. We explore the mechanisms, biocompatibility, and applications of metal-based nanoparticles in photodynamic therapy, highlighting the challenges and the limitations in their use, as well as the combining of metal-based nanoparticles/photodynamic therapy with other strategies as a synergistic therapeutic approach for cancer treatment.

Keywords: biocompatibility; cell death; metal-based nanoparticles; photodynamic therapy; photosensitizer; targeting; toxicity.

Figure 1

Basic PDT type I and type II process schematic diagram. In the type I process, the activated PS interacts directly with cellular components such as lipids, proteins, and nucleic acids. This interaction leads to the transfer of electrons or hydrogen atoms from these cellular components to the excited PS. The transfer results in the formation of ROS, including superoxide anion radicals (O₂⁻•), hydroxyl radicals (•OH), and other radical species. In the type II process, the excited PS transfers its energy directly to molecular oxygen (³O₂) in the surrounding tissue. This energy transfer converts the ground state oxygen (triplet state, ³O₂) to an excited state known as singlet oxygen (¹O₂). ⁰PS: PS ground single state; ¹PS: PS excited singlet state; ³PS: PS excited triplet state; ROS: reactive oxygen species; ¹O₂: singlet oxygen.

Figure 2

Structural overview of an animal cancer cell with its components contributing to its functionality (left). Major pathways of cell death through apoptosis, necrosis, and autophagy, which describe the main processes involved in each pathway (right). This figure was created using BioRender.com.

Figure 3

Biodistribution of MBNPs linked to PS within the tumor microenvironment and the generation of reactive oxygen species (ROS) and singlet oxygen (¹O₂) upon irradiating the tumor site with an appropriate wavelength of light. During PDT, NPs enhance oxygen production, leading to a cascade of events that induce programmed cell death in tumor cells.

Figure 4

Different methods for the synthesis of AuNPs.

Figure 5

Bottom-up and top-down methods for nanomaterial synthesis. (1) Synthesis using bulk material in the top-down method; (2) synthesis using atomic structures/molecules in the bottom-up method; (3) green synthesis approaches in bottom-up methods; (4) toxic method for nanomaterial synthesis in bottom-up and top-down methods using physical and chemical approaches; (5) biological sources exploited in the bioformulation of biogenic (green) nanomaterials; (6) biological plant parts that are used in biogenic nanomaterial synthesis (7); characterization techniques to confirm the synthesis of nanomaterials. Reproduced with permission from Kah et al., Cells, 2023 [75].

Figure 6

(A) Bright field TEM images and electron diffraction of bare MNPs (A–C) and of MNPs functionalized with feroxamine (D–F) [95]. Reproduced with permission from the Royal Society of Chemistry. (B) Representation of functionalized nanoparticles and different attached targeting molecules for property amelioration [96]. Reproduced with permission from the Royal Society of Chemistry.

Figure 7

Advantages and disadvantages of synergistic therapies containing PDT [134]. Reproduced with permission from the Royal Society of Chemistry.