Development and Characterization of Liposomes Containing a Zn(II) Porphyrin Derivative for the Application of Photodynamic Therapy in the Treatment of Breast Cancer

ABSTRACT Objectives This study aims to synthesize and characterize lipid nanosystems (liposomes) for the incorporation of a Zn(II) porphyrin derivative, Zn(II) meso‐tetrakis(N‐n‐hexylpyridinium‐2‐yl)porphyrin (ZnTnHex‐2‐PyP4+, ZnPH), intending to employ an alternative method of treatment, such as photodynamic therapy (PDT), for breast cancer (BC). Methods The system was synthesized using the lipid film hydration technique and characterized by dynamic and electrophoretic light scattering, nanoparticle tracking analysis, and microscopic analysis, in addition to an assay to detect reactive oxygen species (ROS) generation (DPBF) and in vitro assays assessing release percentage and cell viability, in conjunction with an in vivo systemic toxicity study using an Artemia salina model. Results The liposomes exhibited particle diameters ranging from 92.57 to 112.17 nm, a polydispersity index between 0.22 and 0.28, and a zeta potential between −10.56 and −15.33 mV. The ROS generation assay resulted in a quantum yield of 0.19. Cell viability assays showed viability below 35% in 2D models, with confirmation in 3D models. In vitro release studies indicated a modified profile following encapsulation, and in vivo studies using acute toxicity models in A. salina suggested that the formulation is non‐toxic. Conclusion The results demonstrate that the nanostructured systems show promising performance, reinforcing the potential of stimulus‐responsive therapies in the treatment of BC.