Redox-Triggered Gatekeeper-Enveloped Starlike Hollow Silica Nanoparticles for Intelligent Delivery Systems

The design and development of multifunctional carriers for drug delivery based on hollow nanoparticles (HNPs) have attracted intense interests. Ordinary spherical HNPs are demonstrated to be promising candidates. However, the application of HNPs with special morphologies has rarely been reported. HNPs with sharp horns are expected to own higher endocytosis efficiencies than spherical counterparts. In this work, novel starlike hollow silica nanoparticles (SHNPs) with different sizes are proposed as platforms for the fabrication of redox-triggered multifunctional systems for synergy of gene therapy and chemotherapy. The CD-PGEA gene vectors (consisting of beta-CD cores and ethanolamine-functionalized poly(glycidyl methacrylate) (denoted BUCT-PGEA) arms) are introduced ingeniously onto the surfaces of SHNPs with plentiful disulfide bond-linked adamantine guests. The resulting supramolecular assemblies (SHNP-PGEAs) possess redox-responsive gatekeepers for loaded drugs in the cavities of SHNPs. Meanwhile, they also demonstrate excellent performances to deliver genes. The gene transfection efficiencies, controlled drug release behaviors, and synergistic antitumor effect of hollow silica-based carriers with different morphologies are investigated in detail. Compared with ordinary spherical HNP-based counterparts, SHNP-PGEA carriers with six sharp horns are proven to be superior gene vectors and possess better efficacy for cellular uptake and antitumor effects. The present multifunctional carriers based on SHNPs will have promising applications in drug/gene codelivery and cancer treatment.