Autonomous in vitro anticancer drug release from mesoporous silica nanoparticles by pH-sensitive nanovalves.
Mesoporous silica nanoparticles (MSNP) have proven to be an extremely effective solid support for controlled drug delivery on account of the fact that their surfaces can be easily functionalized in order to control the nanopore openings. We have described recently a series of mechanized silica nanoparticles, which, under abiotic conditions, are capable of delivering cargo molecules employing a series of nanovalves. The key question for these systems has now become whether they can be adapted for biological use through controlled nanovalve opening in cells. Herein, we report a novel MSNP delivery system capable of drug delivery based on the function of beta-cyclodextrin (beta-CD) nanovalves that are responsive to the endosomal acidification conditions in human differentiated myeloid (THP-1) and squamous carcinoma (KB-31) cell lines. Furthermore, we demonstrate how to optimize the surface functionalization of the MSNP so as to provide a platform for the effective and rapid doxorubicin release to the nuclei of KB-31 cells.
Meng
Huan
H
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, California 90095, USA.
Xue
Min
M
Xia
Tian
T
Zhao
Yan-Li
YL
Tamanoi
Fuyuhiko
F
Stoddart
J Fraser
JF
Zink
Jeffrey I
JI
Nel
Andre E
AE
D041721:3T3-L1 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D013499:Surface Properties; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000970:Antineoplastic Agents; D047392:beta-Cyclodextrins; D012822:Silicon Dioxide; C031215:betadex