期刊
ACS APPLIED MATERIALS & INTERFACES
卷 8, 期 27, 页码 17166-17175出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b05370
关键词
mesoporous silica nanocarriers; charge reversal; doxorubicin; drug delivery; pH responsive
资金
- Shanghai Municipal Natural Science Foundation [15ZR1408500]
- National Natural Science Foundation of China [31330028]
- 111 Project [B14018]
In this study, we demonstrate a facile strategy (DL-SF) for developing MSN-based nanosystems through drug loading (DL, using doxorubicin as a model drug) followed by surface functionalization (SF) of mesoporous silica nanoparticles (MSNs) via aqueous (3-aminopropyl)triethoxysilane (APTES) silylation. For comparison, a reverse functionalization process (i.e., SF DL) was also studied. The pre-DL process allows for an efficient encapsulation (encapsulation efficiency of similar to 75%) of an anticancer drug [doxorubicin (DOX)] inside MSNs, and post-SF allows in situ formation of an APTES outer layer to restrict DOX leakage under physiological conditions. This method makes it possible to tune the DOX release rate by increasing the APTES decoration density through variation of the APTES concentration. However, the SF-DL approach results in a rapid decrease in drug loading capacity with an increase in APTES concentration because of the formation of the APTES outer layer hampers the inner permeability of the DOX drug, resulting in a burst release similar to that of undecorated MSNs. The resulting DOX-loaded DL-SF MSNs present a slightly negatively charged surface under physiological conditions and become positively charged in and extracellular microenvironment of solid tumor due to the protonation effect under acidic conditions. These merits aid their maintenance of long-term stability in blood circulation, high cellular uptake by a kind of skin carcinoma cells, and an enhanced intracellular drug release behavior, showing their potential in the delivery of many drugs beyond anticancer chemotherapeutics.
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