Silica Nanoparticles: nano-glass! le… · D.-M. Huang et al., Nano Letters, 2007, 7, 149-154 FTIC...
Transcript of Silica Nanoparticles: nano-glass! le… · D.-M. Huang et al., Nano Letters, 2007, 7, 149-154 FTIC...
Silica Nanoparticles: nano-glass!SiO2 nanoparticles
20 nm 70 nm 300 nm
SiO2
SiO2 nanoparticles
1860: colloidal silica discovered by Thomas Graham (sol-gel)
1933: aqueous suspension of colloidal silica produced and commercialized by IG Farben (Germany)
1956: Kolbe observe the formation of silica nanoparticles when tetraethoxysilane (TEOS) is reacted with water in alcohols
1964: Stober and Fink report the controlled polymerization of TEOS in ethanol/water/ammonia
1992: Van Blaadered demonstrates the possibility to include organosilanes in silica nanoparticles.
1998: Arriagada and Osseo-Asare report the reversed emulsion synthesis
2003: Prasad reports the microemulsion synthesis of ORMOSIL nanoparticles
Silica nanoparticles since ever?
SiO2 nanoparticles
Silica nanoparticles everywhere?
SiO2 nanoparticles
Silica nanoparticles everywhere?
…
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Silica nanoparticles: inorganic polymers
CH3 SiCH3
OCH3CH3
CH3 SiCH3
OHCH3
Cat.CH3 Si
CH3O
CH3
SiCH3
CH3
CH3
CH3 SiCH3
OHCH3
CH3 SiCH3
OHCH3
Cat.CH3 Si
CH3O
CH3
SiCH3
CH3
CH3
CH3 SiCH3
OCH3CH3
H2OCH3 Si
CH3OH
CH3Cat.
Hydrolysis
Reactions of ethoxysilanes and silanols
Condensation
H3CO SiOCH3
OCH3
OCH3
H2O
Cat.? Polymerization
Condensation
Nanobiotecnologie
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O SiO
OO
Cat.O Si
OOH
O
O Si
O
OO
O SiO
OO
Si OO
O Cat.O Si
OO
OHSi OO
O
O SiO
OO
? ?
Since silicon is less electronewithdrawing than carbon, oligomer silanols are better nucleophiles than hydrolyzed monomer silanols: growth prevails over nucleation in base catalysis conditions.
Silica nanoparticles: synthesisBase-catalyzed polymerization
Nanobiotecnologie
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Oligomers condensation stops when the total charge is high enough to grant colloidal stability to theparticles. Starting from that moment the particles grow by furter monomer condensation on their surface.
Finale dimensions are essentially controlle by the amount of catalist (ammonia) present in the reactionmedium: ammonia generates salts that increase the ionic stenght of the medium and as a consequencedecreases the colloidal stability of the particles.
OH
OHO
HO
O
O
Oligomer
OH
OHO
HO
O
O
Oligomer
OOH
OOHO
O
HOO
HO SiO
OH
OHO
Hydrolysis of precursor tretalkoxysilane is the rate-determining step. Polymer-monomer reaction is faster than monomer-monomer reaction→ monodisperse particles growth.
However oligomers, once formed, are higlhy unstable and condese to form larger particles.
SiO
O
OO
OH SiO
HO
OHO Si
O
OH
OHO Si
O
HO
OO Si O
HO
OSi
O
OH
OHO
k1 k2
OH
OHO
HO
O
O
Oligomer
Silica nanoparticles: synthesisBase-catalyzed polymerization
Nanobiotecnologie
Silica nanoparticles: preparationSiO2 nanoparticles
SiOH
HO
HOHO Si
OH
OH
HOHO
ion exchange resinO
OH
OOHO
O
HOO
HOM+
M+
M+ M+
M+
SiO
O
OO
OOH
OOHO
O
HOO
HOM+
M+
M+ M+
M+
a) NH3, H2O, EtOH
b) NH3, H2O, AOTn-ottano
SiO
OO
OOH
OOHO
O
HOO
HOM+
M+
M+ M+
M+
NH3, AOT, H2O
water
H2OH2O
HOO O O OH
O
M
M
M pKa ~ 3
~ 4.5 OH / nm2
10-30% Si (T3)
Silica nanoparticlesElectrostatically stabilized nanoparticles
Nanobiotecnologie
SiO2 nanoparticles
Interesting for nanomedicine?
Polymer Metal/Inorganic
Lipid Silica
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70 nm
OHOH
HO O
O
OH
OO
HO
HO
O
O
O
HOHO
HO
HO
O OH OH OOH
OH
OH
OH
O
O
OH
O
SiOO
OO
Si O
SiO
O
Si
SiOO
SiOH
OOH
SiO
SurfaceBulk
Pores• La superficie può essere funzionalizzata con derivati organosilani.• Le pareti dei pori possono essere funzionalizzati con organosilani.• Nei pori e nella matrice possono essere intrappolate molecoleorganiche, specie inorganiche e persino altre nanoparticelle.
• Se si effettuano successive aggiunte di precursori, le particellepossono essere cresciute a stadi.
Silica nanoparticlesPlatforms for multifunctional systems
Nanobiotecnologie
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Etanolo
Si(OEt)4
E’ necessario usare derivati organosilani, ma nelle sintesi con tensioattivi si può ottenere anche intrappolamento sterico.
N
NH N
HNNH
NHO
(EtO)3Si
NH3/H2O
Stober, 1956; van Blaaderen, 1991
Silica nanoparticlesCovalent doping with alkoxysilanes
Nanobiotecnologie
HOO O O OH
O
M
M
M
OHHO
O O O OO
OO O O O
O
SiOR
RO ORF
SiSi
OH
OH
FF
Silica nanoparticlesSurface functionalization
Nanobiotecnologie
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Le nanoparticelle di silice sono trasparenti alla luce epossono essere drogate con molecole organiche. E’quindi semplice produrre nanoparticelle di silicefluorescenti:
• Il fluoroforo protetto dal solvente: maggior resaquantica.
• Il fluoroforo è protetto dall’ossigeno: fotobleachingridotto.
• La particella contiene decine di fluorescenti: maggiorluminosità (brightness)
NBD
Silica nanoparticlesFluorescent nanoparticles
Nanobiotecnologie
DNA microarrays
Fluorescent silica nanoparticlesNanoparticle-enhances assays
Nanobiotecnologie
Sandwich fluorescence immunoassays (FIA)
TEM micrograph of 70 nm silica particles dopedwith FTIC-APTES and surface functionalized withTAT peptide
Fluorescence microscope images of human lungadenocarcinoma cells after incubation withnanoparticles with (left) and without TAT peptide W. Tan et al., Chem. Commun., 2004, 2810-2811
PO32-
PO32-
PO32-
PO32-
PO32-
PO32-
PO32-
PO32-
PO32-
PO32-
PO32-
= GRKKRRQRRR (TAT)
=
O
COOH
HNHN
S
Si(OEt)3
OHHO
FTIC-APTES
Fluorescent silica nanoparticlesFluorescence imaging
Nanobiotecnologie
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microelettrodo Nano-sonda
pH
Fluorescent silica nanoparticlesFluorescence probes
Nanobiotecnologie
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1995: approvazione della FDA per l’applicazione oncologica
Terapia antitumorale che si avvale dell’utilizzo di:
- fotosensibilizzatore
- luce
- ossigeno molecolare
1PS
1PS*
3PS*
3O2
1O2*h IMAGING
CITOTOSSICITA’
Fluorescent silica nanoparticlesFluorescence probes
Nanobiotecnologie
VTES
Tween/H2O+
m-THPC
Dialisis
Singlet oxygen production Cells viability after irradiation
P.N. Prasad et al., Nano Lett, 2007, 7, 2835-2842
Fluorescent silica nanoparticlesPDT agents
Nanobiotecnologie
850 nm
Singlet oxygen
P.N. Prasad et al., JACS, 2007, 129, 2269-2275
Transmission images of HeLa cells treated with NP before (c) and after (d) irradiation at 850 nm
Absorption and emission spectra of the two dyes
Fluorescent silica nanoparticlesPDT agents
Nanobiotecnologie
Nanoparticles@nanoparticlesSilica encapsulation
Nanobiotecnologie
OH
OHO
HO
O
O
Oligomer
OH
OHO
HO
O
O
Oligomer
OOH
OOHO
O
HOO
HO SiO
OH
OHO
Since polymer-monomer reaction is faster than monomer-monomer reaction, monomers added to a basic solution of an appropriate template may lead to the formation of a silica shell.
D.-M. Huang et al., Nano Letters, 2007, 7, 149-154
FTIC
SiO2Fe3O4Schematic structure (up) and TEM micrograph of FTIC-APTES doped 50 nmsilica particles entrapping 10-nm Fe3O4 nanoparticles
A) Fluorescence microscope imagesof human mesenchymal stem cells(hMSCs) after incubation withnanoparticles (green) and alysosomes probe
B) MRI images of a nude mouse withinjected SiO2@Fe3O4nanoparticles
A
B
Iron oxide@silicaMultimodal imaging
Nanobiotecnologie
W. Tan et al., Anal. Chem. 2007, 79, 3075-3082
Iron oxide@silicaIn vitro cell detection and separation
Nanobiotecnologie
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C. Riviere, S. Roux et al., JACS, 2007, 129, 5076-5084
FTIC
SiO2Gd2O3
PEG
MRI images of a nude mouse withinjected SiO2@Gd2O3 nanoparticles B
AFluorescence reflectance images of a nude mouseafter injection of SiO2@Gd2O3 nanoparticles
Gadolinium oxide@silicaMultimodal imaging
Nanobiotecnologie
Drug relase modes
TEM micrograph of hollow mesoporous silica nanoparticles
IBU release in simulated stomach (pH 1.4) and intestinal (pH 8) fluids
J. Shi et al., Angew. Chem. Int. Ed., 2005, 44, 5083-5087
Latex@silica@layer-by-layer polymerControlled drug release
Nanobiotecnologie
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Alcuni tensioattivi in elevata concentrazione formano strutture tubolari impaccate
Tali strutture funzionano come stampi per la produzione di materiali mesoporosi
Sintesi di silice mesoporosa MCM-41
Mesoporous silicaSurfactant aggregates templated synthesis
Nanobiotecnologie
Mesoporous silicaSurfactant aggregates templated synthesis
Nanobiotecnologie
• Surfactant: CTAB (cationic)
• Silica precursor: TEOS
• Catalyst: NaOH
• Solvent: water
• Co-precursor: organosilane (12%)
• Surfactant removal: calcination or HCl extraction
• The use of the co-precursor allows shape control
Mesoporous silicaSurfactant aggregates templated synthesis
Nanobiotecnologie
1. Tunable particle size. The particle size of MSN can be tuned from 50 to 300 nm allowing a facile endocytosis by living animal and plant cells without any significant cytotoxicity.
2. Stable and rigid framework. Compared to other polymer-based drug carriers, MSN is more resistant to heat, pH, mechanical stress, and hydrolysis-induced degradations.
3. Uniform and tunable pore size. The pore size distribution of MSN is very narrow and the pore diameter can be tuned between 2 and 6 nm. These features allow one to adjust the loading of different drug molecules and to study the kinetics of drug release with high precision.
4. High surface area and large pore volume. As mentioned previously, the total surface area (> 900 m2/g) and pore volume (> 0.9 cm3/g) are very large, which allows high loadings of drug molecules.
5. Two functional surfaces. MSN have an internal surface (i.e., cylindrical pores) and an external surface (i.e. exterior particle surface). This characteristic allows the selectively functionalization of the internal and/or external surfaces of MSN with different moieties.
6. Unique porous structure. MSN is comprised of honeycomb-like, 2D hexagonal porous structure with cylindrical pores running from one end of the sphere to the other. There is no interconnectivity between individual porous channels.
Mesoporous silicaGatekeeping delivery
Nanobiotecnologie
The DTT-induced release profiles of Vancomycin and ATP from the CdS-capped MSN system upon DTT addition
Ca2+ efflux in astrocites upon incubation with ATP loaded MSN after addition of mercaptoethanol
Mesoporous silicaGatekeeping delivery
Nanobiotecnologie
TEM images of MSN (a), iron oxide particles (b), capped MSN (c)
HeLa cells incubated with fluorescein loaded MSN
Lin S-J et al., JACS, 2004, 126, 13216-13217
TEM
TEM
Confocal microscpe
Mesoporous silicaGatekeeping delivery
Nanobiotecnologie
Mesoporous silicaNanimpellers/nanovalves
Nanobiotecnologie
Apoptosis of PANC-1 incubated with MSNP induced by releasing CPT after irradiating for increasing times
Mesoporous silicaNanimpellers/nanovalves
Nanobiotecnologie
KB-31 cancer cells endocytosed doxorubicin-loaded fluorescein-labeled MSNPs within 3 h.This action is followed by doxorubicin releaseto the nucleus, induction of cytotoxicity, and theappearance of apoptotic bodies after 60 h(indicated by arrows), followed by nuclearfragmentation after 80 h.
Mesoporous silicaNanimpellers/nanovalves
NanobiotecnologieBefore magnetic field activation(viability 100%)
MPN loaded with Fl+ magnetic field(viability 84%)
MPN loaded with Dox+ magnetic field(viability 63%)
apoptotic bodies
Nanoparicles@Mesoporous silicaNanobiotecnologie
• CTAB can act both as water solubilizing agent and pore template.
• Different nanoparticles can be encapsulated by retaining their properties.
a) Iron oxide np
b) Iron oxide nanowires
c) MnO np
d) Fe3O4 np and CdSe np
Nanoparicles@Mesoporous silicaTheranostic agents
Nanobiotecnologie
Fe3O4@mSiO2
Nanoparicles@Mesoporous silicaTheranostic agents
Nanobiotecnologie
HMn@mSiO2
mSiO2@Fe3O4