Charge-Reversal APTES-Modified Mesoporous Silica Nanoparticles with High Drug Loading and Release Controllability.
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 ∼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.
Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, and Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology , Shanghai 200237, People's Republic of China.
Yifeng
Y
Wang
Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, and Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology , Shanghai 200237, People's Republic of China.
Yi
Y
Sun
Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, and Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology , Shanghai 200237, People's Republic of China.
Jine
J
Wang
Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, and Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology , Shanghai 200237, People's Republic of China.
Yang
Y
Yang
Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, and Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology , Shanghai 200237, People's Republic of China.|Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology , Shanghai 200237, People's Republic of China.
Yulin
Y
Li
Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, and Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology , Shanghai 200237, People's Republic of China.
Yuan
Y
Yuan
Key Laboratory for Ultrafine Materials of Ministry of Education, The State Key Laboratory of Bioreactor Engineering, and Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology , Shanghai 200237, People's Republic of China.
Changsheng
C
Liu
D004317:Doxorubicin; D004337:Drug Carriers; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles; D016062:Porosity; D012822:Silicon Dioxide
D004337:Drug Carriers; D012822:Silicon Dioxide; D004317:Doxorubicin
charge reversal; doxorubicin; drug delivery; mesoporous silica nanocarriers; pH responsive