Acidity-activatable dynamic halloysite nanotubes as a drug delivery system for efficient antitumor therapy

An intelligent drug delivery system allows temporal, spatial and dose control of drug release, which is greatly important in cancer therapy. However, the low stability of the carrier and poor controllability of the anticancer drug may limit its biomedical application. To overcome these drawbacks, an acidity-activated dynamic halloysite nanotubes (HNTs) drug delivery system was designed to ensure efficient cancer therapy. HNTs are first modified with an aminosilane crosslinker, via (3-aminopropyl) trimethoxysilane (APTES). The latter was a linker to convert partial amino groups to hydrazone groups through stepwise organic transformations. Then, the anticancer drug, doxorubicin (DOX), is loaded through a covalent linkage to yield HNTs-NN-DOX. Finally, the soybean phospholipid (SP) is coated on the surface of HNTs-NN-DOX, named HNTs-NN-DOX@SP to further enhance the stability and biocompatibility of HNTs. The acid-labile bond between the HNTs and DOX releases drugs immediately in response to the tumor microenvironment (TME). In vitro cell toxicity and imaging assay results indicated that the HNTs-NN-DOX@SP has high cell cytotoxicity on 4T1 cells. We provide a new strategy for the biomedical application of HNTs in nanomedicine, which proved that HNTs selective to slight pH differences and promote release of cytotoxic compounds.