期刊
ACS APPLIED NANO MATERIALS
卷 1, 期 4, 页码 1976-1984出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsanm.8b00486
关键词
self-decomposition; doxorubicin@silica; radial mesopores; nuclear targeting; combination therapy
资金
- National Natural Science Foundation of China [81371627, 81220108012]
- Program for New Century Excellent Talents in the University of the Ministry of Education of China [NCET-12-0974]
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 SD:), (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 chemophotodynamic 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.
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