Stimuli-Responsive Drug-Delivery Systems Based on Supramolecular Nanovalves

Abstract

There is a growing demand for smart drug-delivery systems to meet the complicated requirements in biomedical applications. Supramolecular nanovalves have been used to regulate the transportation of drug molecules by reversible linkage of multiple components, which have paved an advanced way to construct gated materials for controlled drug release. Supramolecular therapeutics has been developing rapidly, addressing the limitation of uncontrollability and severe side effects of the present pharmacotherapy techniques. In view of their stimuli-responsive and reversible features, supramolecular ensembles including supramolecular polymers and supramolecular pseudorotaxanes, which can act as nanovalves, have been ingeniously introduced to fabricate multifunctional cargo delivery systems for cancer/gene therapy and antibacterial purpose. A reliable therapeutic delivery platform is determined by the selection of biocompatible solid supports to carry and suitable triggers to release therapeutic molecules. In this review, we summarize the recent progress in supramolecular nanovalves and present their applications in cancer/gene therapy and antibacterial regulations. From motor proteins to molecular machines, supramolecular chemistry has been revealed as a remarkable link to bridge the gap between biology, chemistry, and materials. Taking inspiration from the dynamic, reversible, and directional manner of non-covalent interactions that can respond to diversiform external stimuli, supramolecular nanovalves installed on the surface of inorganic or hybrid nanocarriers have received extensive attention in stimuli-responsive delivery of small drug molecules, implying their outspread bioapplications in cancer/gene therapy, biomedical application, and antimicrobial regulations. The state of supramolecular nanovalves could be well regulated by switching the conformation or the assembled/disassembled state of the assemblies. This tutorial review lays the foundation for a better understanding of the significant and typical intelligent drug-delivery systems immobilized with supramolecular polymers or supramolecular pseudorotaxanes as the gating entities of nanovalve-based molecular machines, by showing their chemical structures, operation modes, and release modalities triggered by various actuations at molecular scale. In particular, relevant perspectives of supramolecular therapeutics will also be elaborated upon. From motor proteins to molecular machines, supramolecular chemistry has been revealed as a remarkable link to bridge the gap between biology, chemistry, and materials. Taking inspiration from the dynamic, reversible, and directional manner of non-covalent interactions that can respond to diversiform external stimuli, supramolecular nanovalves installed on the surface of inorganic or hybrid nanocarriers have received extensive attention in stimuli-responsive delivery of small drug molecules, implying their outspread bioapplications in cancer/gene therapy, biomedical application, and antimicrobial regulations. The state of supramolecular nanovalves could be well regulated by switching the conformation or the assembled/disassembled state of the assemblies. This tutorial review lays the foundation for a better understanding of the significant and typical intelligent drug-delivery systems immobilized with supramolecular polymers or supramolecular pseudorotaxanes as the gating entities of nanovalve-based molecular machines, by showing their chemical structures, operation modes, and release modalities triggered by various actuations at molecular scale. In particular, relevant perspectives of supramolecular therapeutics will also be elaborated upon. Supramolecular chemistry continues to scale new heights in science on account of the profound insight into the microscopic world for the advancement of healthcare and frontier science.1García-López V. Chen F. Nilewski L.G. Duret G. Aliyan A. Kolomeisky A.B. Robinson J.T. Wang G. Pal R. Tour J.M. Molecular machines open cell membranes.Nature. 2017; 548: 567-572Crossref PubMed Scopus (187) Google Scholar, 2Yu G. Wu D. Li Y. Zhang Z. Shao L. Zhou J. Hu Q. Tang G. Huang F. A pillar[5]arene-based [2]rotaxane lights up mitochondria.Chem. 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On the other hand, the obtained supra-assemblies relying on molecular recognition are capable of encapsulating drug molecules and achieving controllable stimuli-responsive release upon environmental variation, such as competitive agents, light irradiation, and thermal heating, to disassemble the delivery systems; this has opened new avenues for the development of supramolecular biomedicine. The scope of this review will focus on the recent advances of supramolecular nanovalves and their applications in biomedical fields, represented by drug/gene delivery for tumor therapy and antimicrobial regulation. An advanced survey of newly reported switchable devices for the delivery of therapeutic payloads has also been delineated. For a better understanding of the release profile, we will highlight the construction of nanovalves and disassembly behaviors in response to different types of external stimuli. Figure 2 shows the recent progress of such supramolecular drug-delivery systems. 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