Size-Controlled Synthesis of Porphyrinic Metal–Organic Framework and Functionalization for Targeted Photodynamic Therapy

TLDR

Nanomaterials for targeted cancer therapy are important because their physical parameters strongly influence cellular responses, yet few platforms allow precise molecular‑level tuning of nanoparticle cores. This study demonstrates targeted photodynamic therapy using Zr(IV)-based porphyrinic metal‑organic framework nanoparticles. By a bottom‑up design, the MOF nanoparticle size was precisely tuned across a broad range through selection of building blocks and functional motifs. The porphyrinic linker’s properties remain intact across sizes, and size‑dependent cellular uptake enabled identification of an optimal MOF size that outperformed the small‑molecule photosensitizer; post‑synthetic modification of Zr6 clusters further enhanced targeting and PDT efficacy, demonstrating that size‑controlled MOFs are a versatile platform for advanced photodynamic therapy.

Abstract

The understanding of nanomaterials for targeted cancer therapy is of great importance as physical parameters of nanomaterials have been shown to be strong determinants that can promote cellular responses. However, there have been rare platforms that can vastly tune the core of nanoparticles at a molecular level despite various nanomaterials employed in such studies. Here we show targeted photodynamic therapy (PDT) with Zr(IV)-based porphyrinic metal-organic framework (MOF) nanoparticles. Through a bottom-up approach, the size of MOF nanoparticles was precisely tuned in a broad range with a designed functional motif, built upon selection of building blocks of the MOF. In particular, molecular properties of the porphyrinic linker are maintained in the MOF nanoparticles regardless of their sizes. Therefore, size-dependent cellular uptake and ensuing PDT allowed for screening of the optimal size of MOF nanoparticles for PDT while MOF nanoparticle formulation of the photosensitizer showed better PDT efficacy than that of its small molecule. Additionally, Zr6 clusters in the MOF enabled an active targeting modality through postsynthetic modification, giving even more enhanced PDT efficacy. Together with our finding of size controllability covering a broad range in the nano regime, we envision that MOFs can be a promising nanoplatform by adopting advanced small molecule systems into the tunable framework with room for postsynthetic modification.