Self-Decomposable Mesoporous Doxorubicin@Silica Nanocomposites for Nuclear Targeted Chemo-Photodynamic Combination Therapy Jie Wang Dajun Xu Tao Deng Yunyan Li Le Xue Tong Yan Dechun Huang Dawei Deng 10.1021/acsanm.8b00486.s001 https://acs.figshare.com/articles/journal_contribution/Self-Decomposable_Mesoporous_Doxorubicin_Silica_Nanocomposites_for_Nuclear_Targeted_Chemo-Photodynamic_Combination_Therapy/6086885 Concerns associated with the nondegradability of silica (SiO<sub>2</sub>)-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 SiO<sub>2</sub> nanoparticles (NPs), self-decomposable drug-embedded SiO<sub>2</sub> 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 SiO<sub>2</sub> (mDOX@SiO<sub>2</sub>) 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 SiO<sub>2</sub>-based drug carriers. 2018-03-30 00:00:00 vivo antitumor efficacy drug carriers self-decomposable toxicity NP mesoporous DOX-embedded SiO 2 SiO 2 nanoparticles MB chemo-photodynamic combination therapy molecule mesopore Nuclear Targeted Chemo-Photodynamic Combination Therapy Concerns localization signal peptides