Issue 1, 2020

Single-molecule nanoscale drug carriers with quantitative supramolecular loading

Abstract

While there are examples of successful nanomedicine technologies, challenges remain in engineering systems with controlled and defined characteristics such as size and drug loading. Dendrimers are a class of synthetic macromolecules which offer routes to precise nanoscale objects. Here, highly efficient and orthogonal methods for dendrimer synthesis are combined with the covalent attachment of a tunable number of cucurbit[7]uril macrocycle carriers. This synthetic macrocycle affords uniquely high-affinity binding to certain guests, lending modularity to the prepared dendrimer in terms of its drug cargo. To verify this concept, the chemotherapeutic doxorubicin was conjugated to a high-affinity guest for CB[7]. When combined with CB[7]-modified dendrimers, quantitative drug loading was realized, with one drug bound per CB[7] on the dendrimer. The guest-modified drug was attached via a pH-labile linker to facilitate release at sites of disease or upon cell internalization. This approach offers a new combination of discrete and efficient synthetic methodology coupled with modular and high-affinity supramolecular motifs to engineer platforms with exceptional precision for use in drug delivery.

Graphical abstract: Single-molecule nanoscale drug carriers with quantitative supramolecular loading

Supplementary files

Article information

Article type
Paper
Submitted
29 юли 2019
Accepted
21 авг 2019
First published
28 авг 2019

Mol. Syst. Des. Eng., 2020,5, 197-204

Single-molecule nanoscale drug carriers with quantitative supramolecular loading

L. Zou, M. A. VandenBerg and M. J. Webber, Mol. Syst. Des. Eng., 2020, 5, 197 DOI: 10.1039/C9ME00088G

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