Abstract
The performance of photodynamic therapy (PDT) depends on the solubility, pharmacokinetic behaviors, and photophysical properties of photosensitizers (PSs). However, highly conjugated PSs with strong reactive oxygen species (ROS) generation efficiency tend to have poor solubility and aggregate in aqueous environments, leading to suboptimal PDT performance. Here, we report a new strategy to load highly conjugated but poorly soluble zinc-phthalocyanine (ZnP) PSs in the pores of a Hf12-QC (QC = 2″,3′-dinitro-[1,1’:4′,1”;4″,1’”-quaterphenyl]-4,4’”-dicarboxylate) nanoscale metal–organic framework to afford ZnP@Hf-QC with spatially confined ZnP PSs. ZnP@Hf-QC avoids aggregation-induced quenching of ZnP excited states to significantly enhance ROS generation upon light irradiation. With higher cellular uptake, enhanced ROS generation, and better biocompatibility, ZnP@Hf-QC mediated PDT exhibited an IC50 of 0.14 μM and achieved exceptional antitumor efficacy with >99% tumor growth inhibition and 80% cure rates on two murine colon cancer models.
Highlights
The performance of photodynamic therapy (PDT) depends on the solubility, pharmacokinetic behaviors, and photophysical properties of photosensitizers (PSs)
Despite their improved photophysical properties, Pcs have not been widely used for PDT due to their limited synthetic accessibility and their strong tendency to aggregate in biological media.[11]
Nanoscale metal−organic frameworks have recently provided an excellent strategy to deliver porphyrin, chlorin, and bacteriochlorin PSs for PDT.[22−28] With structural tunability, rigidity, and porosity, nMOFs can efficiently load PSs via direct incorporation as bridging ligands, postsynthetic ligand exchange, postsynthetic surface modification, and physical loading into pores.[29−35] These strategies allow isolation or confinement of lipophilic PSs in rigid nMOF structures to reduce aggregation, improve cellular uptake, and reduce photodegradation.[36−41] We hypothesized that nMOFs could be used to encapsulate Pcs to enhance their PDT efficacy
Summary
The performance of photodynamic therapy (PDT) depends on the solubility, pharmacokinetic behaviors, and photophysical properties of photosensitizers (PSs). The confined PSs in ZnP@Hf-QC efficiently absorbed light and avoided aggregation-induced quenching to significantly enhance 1O2 generation and effectively eradicated/regressed colorectal cancer in mouse models. 1H NMR analysis of digested ZnP@Hf-QC showed that the OAc modulator to QC linker ratio was maintained after ZnP loading (Figure S19).
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