DNA-Functionalized Hollow Mesoporous Silica Nanoparticles with Dual Cargo Loading for Near-Infrared-Responsive Synergistic Chemo-Photothermal Treatment of Cancer Cells

Low drug loading, premature drug leakage, and intratumoral genetic heterogeneity are three main challenges that hinder the successful nanotherapeutics-based oncotherapy, as they provide insufficient therapeutic efficacy, systematic adverse effects, and multidrug resistance, respectively. To address these challenges, we herein develop near-infrared (NIR) laser-sensitive DNA-modified hollow mesoporous silica nanoparticles (HMSNs) with dual cargo loading for chemophotothermal combined treatment of tumors. Starting from the zeolitic imidazolate framework-8 (ZIF-8) template, a layer of mesoporous silica is coated on ZIF-8 (ZIF-8@MSNs), and subsequently the template is self-degraded under acidic conditions to obtain HMSNs. It is demonstrated that the as-made HMSNs possesses a well-defined morphology, large hollow cavities, and abundant mesoporous structures. After loading of indocyanine green into HMSNs' core (ICG@HMSNs), the DNA strands, which are composed by sequential cytosine-guanine (CG) base pairs, are then grafted onto the ICG@HMSNs (DNA-ICG@HMSNs) to provide loading sites for anticancer drug doxorubicin (DOX). The as-prepared DOX-inserted DNA-ICG@HMSNs (DOX@DNA-ICG@HMSNs) shows highly efficient transformation of light energy into thermal energy. Additionally, the loading amount of ICG is determined to be 930 mg g(-1) SiO2, which is more than 30 times compared to that in MCM-41-type MSNs. In vitro experiments using HeLa cells demonstrate that this NIR-laser-responsive drug delivery system (DDSs) enables triggerable cargo release, presumably by heat-induced disruption of the modified DNA double strands. Most importantly, in vitro evaluation and preliminary in vivo investigations independently verified that the combination of triggered chemotherapy and NIR-laser-based hyperthermal therapy results in a better therapeutic effect than individual monotherapies. With these superior properties, we expect that these multifunctional DDSs would promote the application of HMSNs in nanomedical applications.