Self-Decomposable Mesoporous Doxorubicin@Silica Nanocomposites for Nuclear Targeted Chemo-Photodynamic Combination Therapy

Concerns associated with the nondegradability of silica (SiO₂)-based nanoplatforms have hindered their potential clinical translation as drug carriers. Hence, in this work, by embedding drug (doxorubicin (DOX) or methylene blue (MB), etc.) molecules into SiO₂ nanoparticles (NPs), self-decomposable drug-embedded SiO₂ NPs were prepared. Importantly, we found that the intermediate morphology during the decomposition depends on the type of the embedded drug molecules, (e.g., DOX results in mesoporous nanostructures; MB results in center-hollowed nanoshells). Second, different from previous studies, the intermediate mesoporous DOX-embedded SiO₂ (mDOX@SiO₂) NPs with radial mesopores were modified with nuclear localization signal peptides to achieve nuclear targeted DOX delivery upon the fragmentation of NPs. Meanwhile, MB (a widely used photosensitizer) was further uploaded into the mesopores to realize chemo-photodynamic combination therapy. At last, in vitro and in vivo antitumor efficacy and toxicity of the as-designed drug-delivery system were evaluated. The results showed that compared with the nontargeting and chemotherapy-only systems, the self-decomposable NPs with nuclear targeting capability and MB loading exhibited enhanced therapeutic efficacy, and no noticeable systemic toxicity was observed, indicating that the present system should be a promising paradigm in the design of SiO₂-based drug carriers.