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 chemo-photothermal 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.