an8b00486_si_001.pdf (959.47 kB)
Self-Decomposable Mesoporous Doxorubicin@Silica Nanocomposites for Nuclear Targeted Chemo-Photodynamic Combination Therapy
journal contribution
posted on 2018-03-30, 00:00 authored by Jie Wang, Dajun Xu, Tao Deng, Yunyan Li, Le Xue, Tong Yan, Dechun Huang, Dawei DengConcerns
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.