Hydrazone-functionalized nanoscale covalent organic frameworks as a nanocarrier for pH-responsive drug delivery enhanced anticancer activity

Abstract

Nanoscale covalent organic frameworks (NCOFs) as emerging drug-delivery nanocarriers have received much attention in biomedicine in recent years. However, there are few reports on the application of pH-responsive NCOFs for drug delivery nanosystems. In this work, hydrazone-decorated NCOFs as pH-triggered molecular switches are designed for efficient cancer therapy. These functionalized NCOFs with hydrazone groups on the channel walls (named NCOFs-NHNH₂) are obtained via a post-synthetic modification strategy. Subsequently, the anticancer drug doxorubicin (DOX) as the model molecule is loaded through covalent linkage to yield NCOFs-NN-DOX. Finally, soybean phospholipid (SP) is coated on the surface of HNTs-NN-DOX, named NCOFs-NN-DOX@SP, to further enhance the dispersibility, stability and biocompatibility of HNTs in physiological solution. NCOFs-NN-DOX@SP showed an excellent and intelligent sustained-release effect with an almost sixfold increase at pH = 5.2 than at pH = 7.4. In vitro cell toxicity and imaging assays of NCOFs-NN-DOX@SP exhibited an enhanced therapeutic effect on Lewis lung carcinoma (LLC) cells, demonstrating that the fabricated NCOFs have a great potential in cancer therapy. Thus, this work provides a new way toward designing stimulus-responsive functionalized NCOFs and promotes their potential application as an on-demand drug delivery system in the field of cancer treatment.