Fabrication of acetylated carboxymethylcellulose coated hollow mesoporous silica hybrid nanoparticles for nucleolin targeted delivery to colon adenocarcinoma

Abstract

To efficiently deliver the chemotherapeutics to the tumor tissue and minimize the associated adverse effects, nucleolin targeted hybrid nanostructure based on hollow mesoporous silica nanoparticles (HMSNs) were fabricated. To provide the controlled, sustained drug release and enhance blood circulation, the surface of doxorubicin-encapsulated HMSNs were coated with acetylated carboxymethyl cellulose (Ac-CMC) and then covalently conjugated to AS1411 aptamer for guided drug delivery to nucleolin overexpressed cancerous cells. In vitro cellular uptake and cytotoxicity studies confirmed that AS1411 aptamer specifically targets nucleolin overexpressing MCF-7 and C26 cells. Moreover, the in vivo tumor inhibitory effect of AS1411 aptamer conjugated formulation demonstrated a superior therapeutic efficiency over non-targeted formulation and free doxorubicin. The current study might open a new insight to the development of targeted intelligent hybrid materials based on AcCMC-coated HMSNs with high loading capacity, smart characteristics and desirable anticancer potential.

Keywords: AS1411; Acetylated carboxymethyl cellulose; Doxorubicin; Hollow mesoporous silica nanoparticles; Targeted drug delivery.