Supramolecular Organic Framework that Enables Multifunctional Doxorubicin Delivery, Photofrin Post-treatment Phototoxicity Inhibition, and Heparin Neutralization.

Abstract

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