Bis-clickable Mesoporous Silica Nanoparticles: Straightforward Preparation of Light-Actuated Nanomachines for Controlled Drug Delivery with Active Targeting.
Bis(clickable) mesoporous silica nanospheres (ca. 100 nm) were obtained by the co-condensation of TEOS with variable amounts (2-5 % each) of two clickable organosilanes in the presence of CTAB. Such nanoparticles could be easily functionalized with two independent functions using the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction to transform them into nanomachines bearing cancer cell targeting ligands with the ability to deliver drugs on-demand. The active targeting was made possible after anchoring folic acid by CuAAC click reaction, whereas the controlled delivery was performed by clicked azobenzene fragments. Indeed, the azobenzene groups are able to obstruct the pores of the nanoparticles in the dark whereas upon irradiation in the UV or in the blue range, their trans-to-cis photoisomerization provokes disorder in the pores, enabling the delivery of the cargo molecules. The on-command delivery was proven in solution by dye release experiments, and in vitro by doxorubicin delivery. The added value of the folic acid ligand was clearly evidenced by the difference of cell killing induced by doxorubicin-loaded nanoparticles under blue irradiation, depending on whether the particles featured the clicked folic acid ligand or not.
Institut Charles Gerhardt Montpellier, UMR 5253 CNRS, Université de Montpellier-ENSCM, 8, rue de l'école normale, 34296, Montpellier, France.
Achraf
A
Noureddine
Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, Faculté de Pharmacie, Université de Montpellier, 15 Avenue Charles Flahault, 34093, Montpellier cedex 05, France.
Magali
M
Gary-Bobo
Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, Faculté de Pharmacie, Université de Montpellier, 15 Avenue Charles Flahault, 34093, Montpellier cedex 05, France.
Laure
L
Lichon
Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, Faculté de Pharmacie, Université de Montpellier, 15 Avenue Charles Flahault, 34093, Montpellier cedex 05, France.
Marcel
M
Garcia
Department of Chemistry and Biochemistry, California NanoSystems Institute, University of California, Los Angeles, California, 90095-1569, USA.
Jeffrey I
JI
Zink
Institut Charles Gerhardt Montpellier, UMR 5253 CNRS, Université de Montpellier-ENSCM, 8, rue de l'école normale, 34296, Montpellier, France. michel.wong-chi-man@enscm.fr.
Michel
M
Wong Chi Man
Univ. Grenoble Alpes, Inst NEEL, 38042, Grenoble, France. xavier.cattoen@neel.cnrs.fr.|CNRS, Inst NEEL, 38042, Grenoble, France. xavier.cattoen@neel.cnrs.fr.
Xavier
X
Cattoën
D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D001391:Azo Compounds / Q000737:chemistry*; D057930:Click Chemistry; D061565:Cycloaddition Reaction; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008024:Ligands; D053758:Nanoparticles / Q000737:chemistry*; D054118:Nanospheres / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*
D000480:Alkynes; D001386:Azides; D001391:Azo Compounds; D008024:Ligands; D012822:Silicon Dioxide; D004317:Doxorubicin; C009850:azobenzene
CuAAC; click chemistry; drug delivery; mesoporous silica nanoparticles; targeting