Abstract

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

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