Voltage/pH-Driven Mechanized Silica Nanoparticles for the Multimodal Controlled Release of Drugs.
The major challenges of current drug delivery systems for combination chemotherapy focus on how to efficiently transport drugs to target sites and release multiple drugs in a programmed manner. Herein, we report a novel multidrug delivery system, MSNPs 1, based on mechanized silica nanoparticles, which were constructed through functionalization of mesoporous silica nanoparticles with the acid-cleavable intermediate linkages and the monoferrocene functionalized β-cyclodextrin (Fc-β-CD) as supramolecular nanovalves. MSNPs 1 achieved zero premature release in the physiological pH solution and realized two different release modalities. In modality 1, MSNPs 1 released the encapsulated drugs gemcitabine (GEM) and doxorubicin (DOX) in sequence when they were successively applied to voltage and acid stimuli. The release time and dosage of GEM were precisely controlled via external voltage. The subsequent acid-triggered release of DOX was attributed to breakage of the intermediate linkages containing ketal groups. Modality 2 is the concurrent release of these two drugs directly upon acid exposure. Furthermore, the cell viability experiments demonstrated that MSNPs 1 had an improved cytotoxicity to MCF7 cells in comparison with single DOX- or GEM-loaded mechanized silica nanoparticles. We envisage that MSNPs 1 will play an important role in research and development for a new generation of controlled-release drug delivery system.
School of Chemical Engineering and ‡Institute of Computation in Molecular and Materials Science and Department of Chemistry, Nanjing University of Science and Technology , Nanjing 210094, P. R. China.
Ting
T
Wang
School of Chemical Engineering and ‡Institute of Computation in Molecular and Materials Science and Department of Chemistry, Nanjing University of Science and Technology , Nanjing 210094, P. R. China.
GuangPing
G
Sun
School of Chemical Engineering and ‡Institute of Computation in Molecular and Materials Science and Department of Chemistry, Nanjing University of Science and Technology , Nanjing 210094, P. R. China.
MingDong
M
Wang
School of Chemical Engineering and ‡Institute of Computation in Molecular and Materials Science and Department of Chemistry, Nanjing University of Science and Technology , Nanjing 210094, P. R. China.
BaoJing
B
Zhou
School of Chemical Engineering and ‡Institute of Computation in Molecular and Materials Science and Department of Chemistry, Nanjing University of Science and Technology , Nanjing 210094, P. R. China.
JiaJun
J
Fu
D002151:Calorimetry; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D004560:Electricity; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D012822:Silicon Dioxide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D000093542:Gemcitabine
D003692:Delayed-Action Preparations; D003841:Deoxycytidine; D012822:Silicon Dioxide; D004317:Doxorubicin; D000093542:Gemcitabine
acid-cleavable; mechanized silica nanoparticles; multimodal controlled release; supramolecular nanovalves; voltage stimulation