Porphyrinic Metal–Organic Framework PCN-224 Nanoparticles for Colocalization of Nanoparticle-Cargo in the Skin and Enhancement of Sonodynamic Efficacy

Sonodynamic therapy (SDT) is a novel therapeutic modality that is effective for the noninvasive treatment of dermatological diseases. As a ubiquitous large class of sonosensitizers, however, porphyrins suffer from poor skin permeability and the inefficient generation of reactive oxygen species. Herein, different-sized porphyrinic metal–organic frameworks (MOFs), PCN-224 (90, 125, and 200 nm), were developed via the coordination of tetra-kis(4-carboxyphenyl) porphyrin (TCPP) and the metal zirconium to enhance the local delivery of porphyrins, and fluorescent sonosensitizers (methylene blue or rhodamine 6G) were further incorporated to improve the sonodynamic effect, as well as to visualize the delivery of PCN-224 and its cargo. The skin penetration of PCN-224 was found to be increased with the reduction of particle size, and all three-sized samples could overcome the barrier of stratum corneum, even achieving the dermis of the porcine skin. Both intercellular and follicular pathways were noticed for three-sized PCN-224, while the follicular one played a more significant role in the penetration of the smallest PCN-224. The intact nanoparticles were found in the skin. At the initial stage, the nanoparticle and its cargo penetrated the skin as an intact entity, while the encapsulated rhodamine 6G was slowly released to the microenvironment of the skin from the nanoparticle with the prolongation of application. The combination of PCN-224 and methylene blue could increase the acoustically triggered generation of 1 O 2, distinctly boosting the lethal effect against the cancerous cell. Collectively, the study revealed the feasibility of PCN-224 for topical use, suggested an innovative method to enhance the sonodynamic effect, and proposed a possible mechanism for skin drug delivery of MOFs.