Photodynamic therapy (PDT) has emerged as a versatile therapeutic approach in medical fields like ophthalmology, oncology, and dermatology, leveraging the localized production of reactive oxygen species induced by a photosensitizer's interaction with oxygen in biological tissues. Nanocarriers, particularly block copolymer micelles, have been extensively employed to deliver hydrophobic photosensitizers, enhancing their pharmacokinetics and bio-distribution. However, the mechanisms underlying nanocarrier internalization remain unclear, prompting focused studies on copolymer micelle-membrane interactions.
A recent study investigated the efficacy of two copolymer micelles, poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) and poly(ethylene oxide)-block-polystyrene (PEO-PS), in delivering the photosensitizer Pheophorbide a (Pheo). While both micelles exhibited similar capabilities in delivering Pheo to model membranes, PEO-PCL demonstrated higher cellular uptake. Interestingly, this increased uptake did not correspond to improved PDT outcomes, suggesting subtle differences in micellar behavior affecting Pheo delivery.
Furthermore, encapsulating Pheo within PEO-PCL micelles significantly enhanced its cellular responses in human colorectal tumor cells, eliciting notable morphological, mitochondrial, and metabolic alterations. This comprehensive investigation underscores the pivotal role of the photosensitizer's delivery system in shaping therapeutic outcomes, emphasizing the need to consider both components in PDT studies.
Moreover, advancements in understanding photodynamic therapeutic efficiency have extended to the characterization of polymeric self-assemblies, evaluating their purity and morphological diversity. Controlled mixtures of micelles and vesicles demonstrated synergistic effects, surpassing monomorphous systems in PDT efficiency, highlighting the potential superiority of polymorphous vectors in therapeutic applications. Finally, the integration of terahertz spectroscopy into PDT research offers real-time insights into plasma membrane alterations during treatment. By examining early events in membrane permeabilization, this technique provides sensitive, time-resolved information crucial for understanding PDT mechanisms and optimizing therapeutic protocols.
Together, these studies contribute to a deeper understanding of PDT mechanisms, nanocarrier dynamics, and cellular responses, paving the way for improved therapeutic strategies and clinical applications.