Heidi Abrahamse

Catalytic photodynamic therapy is an emerging strategy that integrates enzyme-mimetic nanomaterials with photosensitisers to overcome the intrinsic limitations of conventional photodynamic therapy in solid tumours. Conventional photodynamic therapy relies on the oxygen-dependent generation of cytotoxic reactive oxygen species, which is severely compromised by tumour hypoxia, elevated antioxidant defences, heterogenous photosensitiser accumulation, and limited light penetration. Nanoenzyme-mediated catalytic photodynamic therapy addresses these barriers through two mechanistically distinct catalytic modes: oxygen-generating catalytic photodynamic therapy, in which catalase-like nanoenzymes disproportionate endogenous hydrogen peroxide into molecular oxygen to sustain Type II photochemistry, and oxygen-independent catalytic photodynamic therapy, in which peroxidase/Fenton-like nanoenzymes convert hydrogen peroxide into hydroxyl radicals without requiring oxygen or light activation. Multi-enzyme cascade systems integrate both modes, enabling synergistic reactive oxygen species generation across heterogenous tumour regions. This review discusses the catalytic mechanisms, nanoenzyme classes, including carbon-based materials, metal–organic frameworks, plasmonic nanostructures, and biomimetic systems, and therapeutic applications of catalytic photodynamic therapy. We critically evaluate the evidence linking catalytic activity to improved photodynamic outcomes, highlight methodological limitations in reactive oxygen species assessment, and examine translational challenges including substrate heterogeneity, colloidal scalability, uncontrolled reactive oxygen species generation, and regulatory hurdles. Emerging research directions, including artificial intelligence-mediated nanomaterial design, quantum-guided catalytic optimisation, and immunoengineering, are considered as strategies to accelerate clinical translation.

Chlorin e6-mediated photodynamic therapy and its cellular effects.

Melanoma is the deadliest form of skin cancer, with a rapidly rising incidence and a poor prognosis for patients diagnosed at advanced stages. Photodynamic therapy (PDT) represents a promising, minimally invasive treatment for melanoma. However, its clinical use is often limited by poor tumour selectivity and suboptimal intracellular accumulation of conventional photosensitizers (PSs). To address these challenges, an active targeted photosensitizer nanoparticle that uses pheophorbide-a (Ppa) conjugated with gold nanoparticles (AuNPs) and folic acid (FA) was fabricated. AuNPs serve as nanocarriers with their unique features of high biocompatibility, good photophysical properties, and high load capacity that help in the effective delivery of PSs. AuNPs are attractive nanocarriers for PDT owing to their facile synthesis, surface functionalisation flexibility, excellent biocompatibility, and high stability. These features enable efficient PS loading and facilitate both passive and active targeting, thereby improving the pharmacokinetic profile and therapeutic index of the PS. Folic acid functionalization helps in receptor-mediated targeting through the overexpressed folate receptors on the melanoma cells. The Ppa-AuNP-FA nanobioconjugate was synthesized and characterized for morphology, stability, and photodynamic performance. The phototoxic efficacy of the nanophotosensitiser was tested on three-dimensional (3D) melanoma multicellular tumour spheroids (MCTS), a physiologically relevant model that closely mimics tumour architecture and drug resistance patterns observed in vivo. Optimization studies of free Ppa yielded an IC50 concentration of 9.3 µM, which was used throughout the study. A high concentration of Ppa significantly ruptured spheroids, indicating the need to modify this PS to reduce dose dependency and prevent unwanted side effects in patients. Upon laser irradiation (10 J/cm2), Ppa- AuNP-FA caused significant disruption of the spheroid outer membrane, increased intracellular reactive oxygen species (ROS) production, and induced severe cell death compared to free Ppa and non-targeted controls. The findings from this study demonstrate that the coupling of Ppa with AuNPs and FA greatly improves PS delivery, phototoxicity, and cellular uptake. The Ppa-AuNP-FA complex may become an excellent approach in the active targeting nanotechnology platform for improving PDT in malignant melanoma.

Natural photosensitizers have emerged as promising candidates for photodynamic therapy (PDT) owing to their structural diversity, favorable biocompatibility, and broad biological activities. However, their significance extends beyond their natural origin, as they represent the products of chemo‐biodiversity shaped by millions of years of evolutionary adaptation to diverse ecological pressures. This review examines natural photosensitizers through a chemo‐biodiversity perspective, emphasizing how evolutionary diversification has generated structurally distinct photoactive scaffolds with unique photophysical and photobiological properties relevant to cancer therapy. Attention is given to the relationships between molecular architecture, excited‐state dynamics, reactive oxygen species generation, and therapeutic performance, highlighting how structural features govern photodynamic efficiency and biological responses. The review further discusses how nanotechnology‐based engineering strategies can overcome intrinsic limitations, including poor aqueous solubility, aggregation, photoinstability, and limited tumor selectivity. Recent advances in multifunctional nanoplatforms, molecular engineering, and combination therapies are critically evaluated alongside current translational challenges, including manufacturing, regulatory considerations, and clinical development. By integrating natural product chemistry, photophysics, photobiology, and nanotechnology within a unified conceptual framework, this review demonstrates that chemo‐biodiversity provides a rational foundation for the discovery of next‐generation natural photosensitizers. Harnessing nature's evolutionary molecular diversity offers new opportunities to develop safer, more effective, and clinically translatable photodynamic therapies.

Photobiomodulation (PBM) has gained recognition as a promising, non‐invasive strategy to enhance the differentiation of adipose‐derived stem cells (ADSCs) into smooth muscle cells (SMCs), particularly when used together with a three‐dimensional (3D) hydrogel culture system. This review explores the key mechanisms by which PBM modulates cellular behavior, along with its role in the promotion of SMCs lineage commitment in ADSCs. We investigate the influence of various light parameters including wavelength, intensity, energy density, exposure time and duration on cell responses such as proliferation, metabolic activity, gene expression and functional maturation. Moreover, we scrutinize the different hydrogel scaffolds, their compositions and the respective effects on PBM efficacy and consequential cellular outcomes. We also highlight the importance of scaffold design in mimicking the native extracellular matrix and how along with certain mechanical cues, they play a vital role in supporting stem cell behavior. By identifying current challenges, gaps in the literature and proposing future recommendations; this review aims to provide insights into the optimization of PBM protocols to improve SMCs differentiation of ADSCs, ultimately with the intention of integrating PBM to optimize regenerative therapies for use in regenerative medicine and tissue engineering (TE) strategies for vascular conditions and other smooth muscle‐related diseases.

Diabetes mellitus is a chronic metabolic disorder characterized by the loss or dysfunction of insulin‐producing beta (β) cells. Adipose‐derived stem cells (ADSCs) represent a promising source for generating functional insulin‐producing β cells due to their accessibility and differentiation potential. Photobiomodulation (PBM), a non‐invasive light‐based therapy, has emerged as an innovative strategy to enhance stem cell differentiation efficiency. Evidence suggests that green (525 nm) and near‐infrared (825 nm) wavelengths, applied individually or in combination, can modulate cellular metabolism, ATP production, and differentiation‐related signaling pathways, thereby influencing ADSC commitment toward insulin‐producing β‐cell‐like phenotypes. This in vitro study evaluated the effects of PBM at 525 nm and 825 nm, delivered individually and in combination at energy fluences of 5 J/cm ² and 10 J/cm ² , on the differentiation of ADSCs cultured in β‐cell induction medium into insulin‐producing β‐cell‐like cells under two‐dimensional (2D) culture conditions at 24 h, 5 days, and 10 days. Cellular responses were evaluated using adenosine triphosphate (ATP) luminescence assays, lactate dehydrogenase (LDH) activity assays, Giemsa staining, Live/Dead viability assays, and dithizone (DTZ) staining. ATP levels varied significantly among the experimental groups, reflecting changes in cellular metabolic activity associated with β‐cell induction and PBM exposure, and reduced LDH activity, suggesting decreased cytotoxicity. Giemsa staining revealed morphological changes consistent with β‐cell differentiation, while Live/Dead assays demonstrated the maintenance of cell viability across all experimental groups. Dithizone staining identified the presence of zinc‐rich insulin‐producing clusters. These findings highlight the importance of PBM wavelength and fluence optimization in regenerative stem cell applications.