Supramolecular Organic\nFramework that Enables Multifunctional\nDoxorubicin Delivery, Photofrin Post-treatment Phototoxicity Inhibition,\nand Heparin Neutralization

Although porous frameworks are structurally ideal for\nthe development\nof biomaterials through drug adsorption, sequestration, and delivery,\nintegration of multiple biofunctions into a biocompatible porous framework\nwould greatly improve its potential for preclinical investigations\nby increasing both therapeutic value and research and development\nefficiency. Herein, we report the preparation of a highly biocompatible\nsupramolecular organic framework from an imidazolium-derived tetrahedral\nmonomer and cucurbit[8]uril. The supramolecular organic framework\nhas been revealed to have regular intrinsic porosity and adsorb doxorubicin,\nphotofrin, and heparins driven by hydrophobicity and/or ion-pairing\nelectrostatic interactions. In vivo or in vitro assays illustrate\nthat this adsorption leads to efficient intracellular delivery of\ndoxorubicin, which enhances its antitumor efficacy, elimination of\nphotofrin, which inhibits its post-treatment phototoxicity without\nreducing its photodynamic therapeutic activity, and sequestration\nof (low-molecular-weight) heparins, which neutralizes their anticoagulation\nactivity more efficiently than clinically used protamine.