Mesoporous Silica Nanoparticles Coated by Layer-by-Layer Self- assembly Using Cucurbit[7]uril for in Vitro and in Vivo Anticancer Drug Release

ABSTRACT: Mesoporous silica nanoparticles (MSNs) are promising solid supports for controlled anticancer drug delivery. Herein, we report biocompatible layer-by-layer (LbL) coated MSNs (LbL-MSNs) that are designed and crafted to release encapsulated anticancer drugs, e.g., doxorubicin hydrochloride (DOX), by changing the pH or by adding competitive agents. The LbL coating process comprises bis-aminated poly(glycerol methacrylate)s (BA-PGOHMAs) and cucurbit[7]uril (CB[7]), where CB[7] serves as a molecular bridge holding two different bis-aminated polymeric layers together by means of host−guest interactions. This integrated nanosystem is tuned to respond under specific acidic conditions or by adding adamantaneamine hydrochloride (AH), attributed to the competitive binding of hydronium ions or AH to CB[7] with BA-PGOHMAs. These LbL-MSN hybrids possess excellent biostability, negligible premature drug leakage at pH 7.4, and exceptional stimuli-responsive drug release performance. The pore sizes of the MSNs and bis-aminated compounds (different carbon numbers) of BA-PGOHMAs have been optimized to provide effective integrate