Dimensional Reduction Enhances Photodynamic Therapy of Metal–Organic Nanophotosensitizers

Abstract

Herein we report that dimensional reduction from three-dimensional nanoscale metal–organic frameworks (nMOFs) to two-dimensional nanoscale metal–organic layers (nMOLs) increases the frequency of encounters between photosensitizers and oxygen and facilitates the diffusion of singlet oxygen from the nMOL to significantly enhance photodynamic therapy. The nMOFs and nMOLs share the same M12–oxo (M = Zr, Hf) secondary building units and 5,15-di-p-benzoatoporphyrin (DBP) ligands but exhibit three-dimensional and two-dimensional topologies, respectively. Molecular dynamics simulations and experimental studies revealed that the nMOLs with a monolayer morphology enhanced the generation of reactive oxygen species and exhibited over an order of magnitude higher cytotoxicity over the nMOFs. In a mouse model of triple-negative breast cancer, Hf-DBP nMOL showed 49.1% more tumor inhibition, an 80% higher cure rate, and 16.3-fold lower metastasis potential than Hf-DBP nMOF.

Tuning the aqueous self-assembly of porphyrins by varying the number of cationic side chains

“…As porphyrins are extensively studied for photodynamic therapy (PDT) of tumors, the 2D morphological characteristic of nanosheets would benefit the anti-tumor performance of porphyrin-based nanodrugs. 16,25 However, 2D nano-photosensitizers are relatively rare due to the lack of approaches to prepare water-soluble and biocompatible 2D materials. The 2D nanosheets also display a high photosensitizer loading capacity (78.9% by weight, see calculation in the ESI, † section 2) and good stability in cell culture media (see for TEM image of nanosheets), which are ideal properties for nanophotosensitizers.…”

“…J-Aggregation is potentially capable of driving porphyrins to assemble into 2-dimensional (2D) nanomaterials, which hold specific advantages in materials science for various applications. 7,16 Due to the strong hydrophobicity and tendency to form H-aggregates, it remains a significant challenge to regulate the stacking of porphyrins to form J-aggregates in water. 17 In our previous studies, adding polyphosphates has been demonstrated as an effective approach to inducing the aggregation of cationic conjugated molecules in water, e.g., H-aggregated porphyrins to assemble nanofibers.…”

Molecular Engineering of Metal–Organic Layers for Sustainable Tandem and Synergistic Photocatalysis

“…21,22 The active sites in 2D MOLs are completely accessible to organic substrates. 23,24 Furthermore, the capping monocarboxylate modulators in the vertical direction of the SBUs can be modified with active sites via carboxylate exchange to form multifunctional MOLs for catalytic transformations. 25 This strategy has been successfully used to design MOLs for photoredox dual catalysis.…”

“…In recent work, a porphyrinic Hf 12 -MOL was successfully synthesized by screening a library of monocarboxylate modulators. 24 Tuning the modulator from acetic acid to propionic acid downsized the product from a 3D MOF to a 2D MOL. Further development of synthetic methods for multifunctional MOLs should allow the design of a new generation of sustainable catalysts.…”

“…Despite their great potential for sustainable catalysis, the difficulty in MOL synthesis and characterization presents a significant bottleneck for the further development of MOL catalysts. To date, only Hf 6 and H 12 SBUs have been combined with a limited number of bridging ligands to construct MOLs. ,, Although several 2D MOFs based on Zn, Cu, and Al SBUs have been reported, − they lack stability or cannot be postsynthetically modified for catalytic applications. In recent work, a porphyrinic Hf 12 -MOL was successfully synthesized by screening a library of monocarboxylate modulators .…”