Macrocycle-based self-assembled amphiphiles for co-delivery of therapeutic combinations to tumor

For tumor treatment, the efficiency of single chemotherapeutic agent is generally limited and the traditional combination chemotherapies frequently result in the aggravation of side effects. Herein, an amphiphilic pillararene-based self-assembled nanoparticle (APSN) composed of hydrazide-pillar[5]arene (HP5A-6C) that achieve effective co-delivery of therapeutic combinations was reported. Through integrating multitudinous macrocyclic cavities into a single nanoparticle, the APSN could co-load two antitumor drugs, cisplatin (CP) and nitrogen mustard (NM) via host-guest interactions. A serious of safety tests preliminary demonstrated that blank carrier APSN had good biocompatibility. Cytotoxicity assay verified that co-delivery system CP+NM@APSN could exert a synergistic antitumor effect at the cellular level. In vivo studies demonstrated that CP+NM@APSN could not only improve chemotherapeutic outcomes in tumor-bearing model mouse but also alleviate two medications-related side effects. These favorable findings were attributed to the formation of ternary supramolecular assembly that benefited from an enhanced permeability and retention effect. © 2024 Elsevier Science. All rights reserved.