Silsesquioxane‐Based Highly Biocompatible Supramolecular Organic Framework That Inhibits Photofrin Posttreatment Phototoxicity †

Comprehensive Summary For the first time, polyhedral oligomeric silsesquioxane (POSS) has been used to prepare an octatopic component to co‐assemble with cucurbit[8]uril (CB[8]) at room temperature to afford a three‐dimensional POSS‐based supramolecular organic framework pSOF. Dynamic light scattering experiment reveals that the new highly water‐soluble SOF has concentration‐dependent nano‐scaled sizes, while solution‐ and solid‐phase synchrotron radiation small‐angle X‐ray scattering experiments indicate that the SOF possesses a mesoporosity with an average size of 2.9 nm and a quite large size distribution. Mice model reveals that pSOF adsorbs photofrin and significantly alleviates its post‐treatment phototoxicity, the largest limitation of photofrin as clinically used photodynamic therapeutic agent, but does not impose a negative effect on its photodynamic therapeutic efficacy. The maximum tolerated dose of pSOF for mice is determined to be 170 mg/kg, which is conspicuously higher than the highest value (120 mg/kg) reported for diamondoid‐styled SOFs and endows it with the highest therapeutic index.