Abstract
Mesoporous silica nanoparticle (MSN)-based stimuli-responsive capped drug delivery systems have attracted extensive attention. However, most studies aboutcapping agents only focus on the capping function. Here, a multifunctional capping agent (MFCA) was developed to integrate pore-capping, drug-loading, and tumor-targeting abilities. It was composed of phenylboronic acid (PBA)-modified sodium alginate (ALG) and doxorubicin (DOX), which were loaded in the channels and conjugated ALG viahydrazone bond through a one-pot method. Consequently, the drug-loading content of obtained nanoparticles (DOX@MSN-ALG-APBA) reached up to 10.6%, which increased by about 58.2% compared with that of ALG-APBA capped MSNs (i-DOX@MSN-ALG-APBA). The in vitro drug release at pH 7.4 was less than 10% in 3 days, which was comparable to i-DOX@MSN-ALG-APBA. More importantly, the initial accumulative drug release of DOX@MSN-ALG-APBA was about 2-fold than that of i-DOX@MSN-ALG-APBA at pH 6.0. Also, the targeting efficiency of DOX@MSN-ALG-APBA was 2.85-fold than that of DOX@MSN-ALG in vitro after introducing phenylboronic acid. Compared with free DOX and i-DOX@MSN-ALG-APBA, DOX@MSN-ALG-APBA induced remarkable cell apoptosis and inhibition effects in vitro, owing to the rapid release of drug during the initial phase. Overall, it is expected that this integrated strategy is promising to fabricate an excellent MSN-based drug delivery system.
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