Supramolecular Polymer-Based Nanomedicine: High Therapeutic Performance and Negligible Long-Term Immunotoxicity

Nanomedicines have achieved several breakthroughs in cancer treatment over the past decades; however, their potential immunotoxicities are ignored, which results in serious adverse effects and greatly reduces the potential in clinical translation. Herein, we innovatively develop a theranostic supramolecular polymer using β-cyclodextrin as the host and camptothecin (CPT) as the guest linked by a glutathione-cleavable disulfide bond. The supramolecular polymerization remarkably increases the solubility of CPT by a factor of 232 and effectively inhibits its lactone ring opening in physiological environment, which is favorable for intravenous formulation and maintenance of the therapeutic efficacy. Supramolecular nanoparticles can be prepared through orthogonal self-assembly driven by π–π stacking interaction, host–guest complexation, and hydrogen bonds. The sophisticated nanomedicine constructed from the obtained supramolecular polymer can be specifically delivered to tumor sites and rapidly excreted from body after drug release, thus effectively avoiding systemic toxicity, especially long-term immunotoxicity. In vivo investigations demonstrate this supramolecular nanomedicine possesses superior antitumor performance and antimetastasis capability. This pioneering example integrating the advantages of the dynamic nature of supramolecular chemistry and nanotechnology provides a promising platform for cancer theranostics.