Electrospun fibrous architectures for localized delivery of photosensitizers in cancer therapy

Abstract

Photodynamic therapy (PDT) is a promising localized strategy for the treatment of cervical cancer, ranking as the fourth most common cancer among women worldwide. The integration of photosensitizers (PSs) in localized drug delivery systems (DDSs), particularly in electrospun nanofibers, holds tremendous potential to overcome the drawbacks of their systemic administration. Exploring multilayer fibrous architectures provides a versatile therapeutic platform to design the next generation of localized DDS. In this work, localized implants for cancer treatment using PDT were developed using polyhydroxyalkanoate (PHA), chitosan (CS) and polyethylene oxide (PEO) as biopolymers and a porphyrin (Por) as PS, following two approaches: blended PHA/Por electrospun microfibers and multilayered membranes (PHA–Por/CS/PEO) produced by sequential electrospinning. The synthesized Por displayed higher cytotoxicity in light compared to dark against tumor cells. All the developed membranes were characterized regarding their morphology, wettability, absorption and fluorescence properties. PHA–Por membranes exhibited overall uniform fibrous morphologies with successful Por incorporation. Nonetheless, they presented a highly hydrophobic surface, compromising the Por release and cell–material interactions. In contrast, multilayer PHA–Por/CS/PEO membranes demonstrated enhanced hydrophilicity and enabled sustained Por release. Upon light irradiation, these membranes induced a significantly greater inhibition of HeLa cell proliferation (29.61%) compared to dark conditions (6.21%), confirming their photodynamic activity.