Novel functional nanoscale composites on the basis of oligoperoxide surfactants: synthesis and biomedical applications
Principal experimental approaches based on tailored synthesis of oligoperoxide surfaceactive substances and their application for obtaining polymeric and hybrid nanoscale carriers possessing targeted functionality and biocompatibility are presented. Molecular design of novel linear, block and combli...
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Інститут біохімії ім. О. В. Палладіна НАН України
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irk-123456789-39342013-02-13T02:10:40Z Novel functional nanoscale composites on the basis of oligoperoxide surfactants: synthesis and biomedical applications Zaichenko, O. Stoika, R. Mitina, N. Lutsik, M. Shevchuk, O. Lobaz, V. Boiko, N. Експериментальні статті Principal experimental approaches based on tailored synthesis of oligoperoxide surfaceactive substances and their application for obtaining polymeric and hybrid nanoscale carriers possessing targeted functionality and biocompatibility are presented. Molecular design of novel linear, block and comblike oligoperoxide surfactants and derived coordinating complexes of transitional and rare earth metal cations is a convenient tool for synthesis of luminescent, magnetic and other functional nanocomposites with controlled size distribution, functionality, reactivity and biocompatibility. The methods developed provide combining the stage of formation of polymeric, metal and metaloxide nanoparticles with the stage of their surface irreversible modification by functional surfaceactive oligoperoxides capable of binding physiologically active substances. The availability of reactive ditertiary peroxide fragments provides a possibility for functionalization of developed nanoparticles that were applied for studying phagocytosis, surface markers of pathological cells, and targeted delivery of drugs and antimicrobial remedies. Розглянуто основні експериментальні підходи до цілеспрямованого синтезу поверхневоактивних олігопероксидних речовин і їх застосування з метою одержання полімерних і гібридних нанорозмірних носіїв, яким притаманна скерована функціональність та біосумісність. Конструювання нових лінійних, блокових та гребенеподібних олігопероксидних сурфактантів, а також їхніх похідних координаційних комплексів із катіонами перехідних та рідкоземельних металів є зручним інструментом для синтезу люмінесцентних, магнітних та інших функціональних нанокомпозитів із регульованим розподілом за розмірами, функціональністю, реактивністю та біосумісністю. Розроблені методи дозволяють поєднати стадію формування полімерних, металевих та металооксидних наночастинок зі стадією необоротної модифікації їхньої поверхні функціональними поверхнево<активними олігопероксидами, здатними зв’язувати фізіологічно активні речовини. Наявність реакційноздатних дитретинних пероксидних фрагментів уможливлює функціоналізацію створених наночастинок, що їх було застосовано для дослідження фагоцитозу як поверхневі маркери патологічних клітин, а також для спрямованого доставлення лікарських препаратів. Рассмотрены основные экспериментальные подходы к целенаправленному синтезу олигопероксидных поверхностноактивных веществ и их использованию для получения полимерных и гибридных наноразмерных носителей, обладающих заданной функциональностью и биосовместимостью. Конструирование новых линейных, блочных и гребеневидных олигопероксидных сурфактантов, а также их производных координационных комплексов с катионами переходных и редкоземельных металлов является удобным инструментом для синтеза люминесцентных, магнитных и других функциональных нанокомпозитов с регулируемым распределением по размеру, функциональности, реакционной способности и биосовместимости. Разработанные методы обеспечивают совмещение стадии формирования полимерных, металлических и металлооксидных наночастиц со стадией необратимой модификации их поверхности функциональными поверхностноактивными лигопероксидами, способными к связыванию физиологически активных веществ. Наличие реакционноспособных дитретичных пероксидных фрагментов обеспечивает возможность функционализации полученных наночастиц, которые использовались для изучения фагоцитоза как поверхностные маркеры патологических клеток, а также для целевой доставки лекарственных препаратов. 2008 Article Novel functional nanoscale composites on the basis of oligoperoxide surfactants: synthesis and biomedical applications / O. Zaichenko, R. Stoika, N. Mitina, M. Lutsik, O. Shevchuk, V. Lobaz, N. Boiko, // Біотехнологія. — 2008. — Т. 1, № 1. — С. 86-99. — Бібліогр.: 18 назв. — англ. http://dspace.nbuv.gov.ua/handle/123456789/3934 541.64:541.182:541.183 en Інститут біохімії ім. О. В. Палладіна НАН України |
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Експериментальні статті Експериментальні статті |
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Експериментальні статті Експериментальні статті Zaichenko, O. Stoika, R. Mitina, N. Lutsik, M. Shevchuk, O. Lobaz, V. Boiko, N. Novel functional nanoscale composites on the basis of oligoperoxide surfactants: synthesis and biomedical applications |
| description |
Principal experimental approaches based on tailored synthesis of oligoperoxide surfaceactive substances and their application for obtaining polymeric and hybrid nanoscale carriers possessing targeted functionality and biocompatibility are presented. Molecular design of novel linear, block and comblike oligoperoxide surfactants and derived coordinating complexes of transitional and rare earth metal cations is a convenient tool for synthesis of luminescent, magnetic and other functional nanocomposites with controlled size distribution, functionality, reactivity and biocompatibility. The methods developed provide combining the stage of formation of polymeric, metal and metaloxide nanoparticles with the stage of their surface irreversible modification by functional surfaceactive oligoperoxides capable of binding physiologically active substances. The availability of reactive ditertiary peroxide fragments provides a possibility for functionalization of developed nanoparticles that were applied for studying phagocytosis, surface markers of pathological cells, and targeted delivery of drugs and antimicrobial remedies. |
| format |
Article |
| author |
Zaichenko, O. Stoika, R. Mitina, N. Lutsik, M. Shevchuk, O. Lobaz, V. Boiko, N. |
| author_facet |
Zaichenko, O. Stoika, R. Mitina, N. Lutsik, M. Shevchuk, O. Lobaz, V. Boiko, N. |
| author_sort |
Zaichenko, O. |
| title |
Novel functional nanoscale composites on the basis of oligoperoxide surfactants: synthesis and biomedical applications |
| title_short |
Novel functional nanoscale composites on the basis of oligoperoxide surfactants: synthesis and biomedical applications |
| title_full |
Novel functional nanoscale composites on the basis of oligoperoxide surfactants: synthesis and biomedical applications |
| title_fullStr |
Novel functional nanoscale composites on the basis of oligoperoxide surfactants: synthesis and biomedical applications |
| title_full_unstemmed |
Novel functional nanoscale composites on the basis of oligoperoxide surfactants: synthesis and biomedical applications |
| title_sort |
novel functional nanoscale composites on the basis of oligoperoxide surfactants: synthesis and biomedical applications |
| publisher |
Інститут біохімії ім. О. В. Палладіна НАН України |
| publishDate |
2008 |
| topic_facet |
Експериментальні статті |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/3934 |
| citation_txt |
Novel functional nanoscale composites on the basis of oligoperoxide surfactants: synthesis and biomedical applications / O. Zaichenko, R. Stoika, N. Mitina, M. Lutsik, O. Shevchuk, V. Lobaz, N. Boiko, // Біотехнологія. — 2008. — Т. 1, № 1. — С. 86-99. — Бібліогр.: 18 назв. — англ. |
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2025-07-02T07:15:55Z |
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2025-07-02T07:15:55Z |
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| fulltext |
БІОТЕХНОЛОГІЯ, Т. 1, №1, 2008
86
The development of novel nanoparticles
and nanocomposites with polymeric shell
which provides their colloidal stability with
biocompatibility, chemical targeted function<
ality and reactivity as well as the methods of
their synthesis are of a significant interest for
the obtaining nanoscale carriers and labels of
biomedical application [1–3]. A variety of syn<
thetic technologies for the preparation of
nanoparticles of biomedical application with
narrowed size distribution and tailored func<
tionality and reactivity are available [1, 2]. At
the same time nanoparticle targeted irre<
versible surface functionalization is one of the
main problems of the particle synthesis and
biomedical application. As it is referred in [4]
«The ability to assemble nanostructures
requires precise control of the particle’s sur<
face chemistry, where molecules can be coated
onto the surface to direct the assembly
process. Strategies have been developed to
readily permit the modification of a nanopar<
ticle’s surface chemistry. In preparing for
coatings, the surface of metallic nanoparticles
is generally stabilized with a weak ligand that
can be easily desorbed from the surface. For
other types of nanoparticles where the surface
coating with biomolecules may be more diffi<
cult, extra processing steps are needed to cre<
ate a surface with reactive functional groups
(–COOH, –SH, or –NH2)». This can lead to
novel approaches in treatment of cancer, AIDS
and Alzheimer disease.
The creation of theoretical and experimen<
tal bases of the synthesis of novel surfactant
oligoperoxides (SAP) and coordinative oligo<
peroxide metal complexes (OMC) on the basis
of linear, block and branched structures opens
a possibility for obtaining new functional
polymeric, inorganic and hybrid colloidal par<
ticles [5, 6] by the techniques of sorption mod<
ification or/and polymerization. Functional
surface<active SAP and OMC are absorbed
onto the surface of dispersed polymer and
mineral fillers providing the localization of
necessary quantity of hydrophobic or hydro<
philic and peroxide<containing fragments.
A brief review of principally universal
approaches based on tailored synthesis and
reactions of functional oligoperoxide surfac<
tants developed in our laboratory for obtain<
ing and application of functionally active
Principal experimental approaches based on tailored synthesis of oligoperoxide surface<active substances and
their application for obtaining polymeric and hybrid nanoscale carriers possessing targeted functionality and bio<
compatibility are presented. Molecular design of novel linear, block and comb<like oligoperoxide surfactants and
derived coordinating complexes of transitional and rare earth metal cations is a convenient tool for synthesis of lumi<
nescent, magnetic and other functional nanocomposites with controlled size distribution, functionality, reactivity
and biocompatibility. The methods developed provide combining the stage of formation of polymeric, metal and
metal<oxide nanoparticles with the stage of their surface irreversible modification by functional surface<active
oligoperoxides capable of binding physiologically active substances. The availability of reactive ditertiary peroxide
fragments provides a possibility for functionalization of developed nanoparticles that were applied for studying
phagocytosis, surface markers of pathological cells, and targeted delivery of drugs and antimicrobial remedies.
УДК 541.64:541.182:541.183
NOVEL FUNCTIONAL NANOSCALE COMPOSITESNOVEL FUNCTIONAL NANOSCALE COMPOSITES
ON THE BASIS OF OLIGOPEROXIDE ON THE BASIS OF OLIGOPEROXIDE
SURFACTANTS:SURFACTANTS:
SYNTHESIS AND BIOMEDICAL APPLICATIONSSYNTHESIS AND BIOMEDICAL APPLICATIONS
Key words: oligoperoxide surfactants, metal complexes, radical emulsion polymerization, homogeneous
nucleation, functional colloidal particles, «core<shell» polymerization, phagocytosis, drug delivery.
O. Zaichenko1
R. Stoika2 1Lviv Polytechnic National University, Ukraine
N. Mitina1 E$mail: zaichenk@polynet.lviv.ua
M. Lutsik2
O. Shevchuk1 2Institute of Cell Biology of National Academy of Sciences of Ukraine, Lviv
V. Lobaz1
N. Boiko2
Експериментальні статті
87
colloids and nanoparticles predominantly for
biomedical application is the main goal of our
work.
Materials and methods
Oligoperoxide surfactants (SAP) were syn<
thesized on the basis of vinyl acetate (VA),
maleic anhydride (MA), and 5<tert butylper<
oxy<5<methyl<1<hexene<3<yne (VEP), styrene
(St), methyl methacrylate (MMA), N<vinyl
pyrrolidone (N<VP), butyl acrylate (BA),
acrylic acid (AA). Polymerization was conduc<
ted at 333K in ethyl acetate, using azobisiso<
butyronitrile (AIBN) as initiator [5]. Surfac<
tant oligoperoxide metal complexes (OMC)
were obtained by interaction of functional
SAP with copper cations in organic medium at
room temperature [6, see also Fig. 1]. Used
monomers were purified by double vacuum
distillation. MA was purified by vacuum sub<
limation and after purification its melting
point was 325K (ref. [7]). The peroxide
monomer VEP was purified by vacuum distil<
lation (active oxygen content was 8.79%; calc.
8.75%). AIBN was purified by re<crystalliza<
tion from ethanol. Other monomers and sol<
vents (Merck) as well as metal salts were used.
For biological studies nanoparticles of
polystyrene and polybutyl<methacrylate
structure were synthesized via water disper<
sion polymerization initiated by OMC or by
water dispersion copolymerization of styrene
with surface<active monomer (SM). Ammo<
nium persulfate (APS), AIBN, or functional
oligoperoxide metal complex (OMC) were used
as initiators. Besides, colored latexes were
obtained by incorporation of specific dyes
(MD) into particles.
The following latexes were used in the
study of phagocytosis:
– НМ<20 series, polystyrene based polymer:
• Copolymer styrene: SM 100:10 — APS;
• Copolymer styrene: SM 100:10 — AIBN;
• Copolymer styrene: SM 100:1 — AIBN;
• Copolymer styrene: SM 100:1 — APS.
– Latexes with incorporated dye:
• Copolymer styrene: SM 100:10 + 10%
MD, initiator — APS (Viola<1);
• Copolymer styrene: SM 100:10 + 10%
MD, initiator — APS, Т=70оС (Viola<2);
• Copolymer styrene: SM 100:10 + 20%
MD, initiator — APS (Viola<3).
– Polyacrylate based latexes:
• Butyl methacrylate: SM 100:10 +20%
MD, initiator — APS, Т=80 0С (Viola<4);
• Butyl methacrylate: methyl methacrylate
+ glycidyl methacrylate, initiator — OMC.
Fractionation of nanoparticle suspensions
by differential centrifugation
For obtaining monodisperse latexes based on
styrene and acrylate polymers the following
scheme of differential centrifugation was applied
(Fig. 2). The obtained fractions I, II, III were
stored as 10% (v/v) water suspensions in the
presence of 0.02% sodium azide, as preservative.
Fractionation of metallic nickel particles
coated with polymer was performed by sponta<
neous sedimentation for different time inter<
vals. The sedimentation rate at 1 g was high
enough without centrifugation. The suspen<
sion was submitted to ultrasonic treatment for
effective disintegration (dispersion), the li<
quid in a vessel was kept of constant level 7 cm,
fraction of particles which sediment between 4
and 7 min was collected. The procedure was
repeated three times.
Fig. 1. Surface6active oligoperoxide polymeric complexes with metal cations. Radicals R1 and R2 are presented.
Oligoperoxide group is noted with red arrow
; ;;
БІОТЕХНОЛОГІЯ, Т. 1, №1, 2008
88
For light microscopy and micrometry of
particle fractions, the smears were prepared
on microscope slides as follows: 50 µl of sus<
pension was centrifuged in Eppendorf’ tube,
supernatant was discarded, the sediment was
suspended in two volumes of bovine serum and
smears were obtained as conventionally
accepted in hematology. Microscopic investi<
gation was conducted using objective ×40 and
ocular ×15. The size of particle was measured
using an ocular<micrometer AM9–2, 200–300
particles were measured in 3–4 fields and mean
diameter was calculated.
Functionalization of nanoparticles with
specific proteins, opsonization of nanopar[
ticles for phagocytosis
Opsonization of latexes was performed as
following. Aliquot of latex was centrifuged,
the sediment of particles was washed twice
with 0.1 M pyrophosphate buffer pH 8.9 and
The raw latex was homogenized in water using
Potter<Elvehjem homogenizer with a tight pestle
(the space between pestle and cylinder 0.1 mm)
and suspension was adjusted to a concentration
1–1.5% by dilution with water
The suspension was poured into a glass cylinder
to the height of 10 cm and kept for two hours for
spontaneous sedimentation of large particles and
aggregates
Supernatant was collected and centrifuged at
5,000 rpm for 20 min in an angle rotor. The pre<
cipitate was collected and resuspended in water
to concentration 1–1.5%
Centrifugation of suspension at 2.000 rpm
(500 g) in backet<rotor for 15 min
Sediment
suspended in water and cen<
trifuged at 2.000 rpm (500g) for
15 min. Procedure is repeated
three times
Supernatant
Centrifugation at 4.000 rpm
(2.000g) for 15 min
Sediment<fraction I
Sediment
suspended in water
and centrifuged at
4.000 rpm (2.000 g)
for 15 min, procedure
repeated three times
Supernatant
Centrifuged at
5.000 rpm (3.300 g)
for 25 min
Sediment<fraction II Sediment< fraction III
Fig. 2. Scheme of differential centrifugation of monodisperse latexes based on styrene and acrylate polymers
Експериментальні статті
89
was suspended in double volume of human
serum or 0.5% solution of concanavalin A in
the same buffer. Suspension was kept in
refrigerator for 24 hours, thereafter washed
several times with PBS and the final suspen<
sion was standardized according to the number
of particles per ml (usually 400–500 mln/ml).
Isolation of white blood cells
Phagocytosis test was performed on leuko<
cyte suspension of human blood, which was
prepared as follows. In a sterile plastic syringe
1–2 ml of blood was taken with anticoagulant
heparin (0.1 volume of medical heparin solu<
tion diluted 1:10 with sterile saline). There<
after 5% sterile solution of dextrane in saline
was aspirated up to the final concentration of
dextrane 1%, mixed and the syringe at an
angle 450 for 20–30 min. In the presence was
placed of dextrane, the sedimentation of red
blood cells is accelerated, leaving over ery<
throcytes plasma with leukocytes and small
residue of erythrocytes. The volume of plasma
enriched with leukocytes is about half of ini<
tial blood volume. It was carefully transferred
from syringe through plastic capillary tube
into sterile Eppendorf’s plastic tube. In
obtained leukocyte suspension the number of
granulocytes and lymphocytes was deter<
mined by the following way: 20 µl of leukocyte
suspension was taken in an Eppedorf’s tube
and cells were pelleted by centrifugation for
2 min at 1.500 rpm. Plasma was carefully dis<
carded and cells were suspended in 40 µl solu<
tion of 1% acetic acid with 0.5 % methyl green.
After 5 min the suspension was investigated in
hemocytometric unit (Horyaev type) at a mag<
nification ×600 and nuclei of mononuclears and
polymorphonuclears were differentially count<
ed. The number of polymorphonuclears (PMN)
and mononuclears (MN) in 1 µl were calculated.
As traditional object of phagocytosis the
killed cells of yeast Debariomyces hansenii
were used. The suspension was prepared by
dispersion of 1 mg of powder of dried cells in
0.5 ml of water. Effective dispersion was
achieved by multiple passing of suspension
through the finest needle of insulin syringe.
The concentration of particles in suspension
was determined by counting of aliquot diluted
1:50 with water in hemocytometric unit at
magnification ×600. Usually the concentra<
tion 2 mg/ml corresponds to 130–150 mln of
yeast cells per ml. Nevertheless, each series of
suspension should be standardized. For a pro<
long storage (two weeks) suspension is pre<
served with 0.02% of sodium azide.
Experimental procedure
of phagocytosis test
1. 50 µl of leukocyte suspension is placed
in plastic Eppendorf tube, thereafter 1 µl of
particle suspension is added, mixed and incu<
bated at 37 0C for 50–55 min.
2. Tubes are centrifuged at 1.500 rpm for
2 min, supernatants are carefully aspirated
leaving 3–4 µl, in which the precipitated cells
are suspended and smears are prepared on
microscope slides. Smears are fixed in metha<
nol and stained by Romanovsky<Giemsa
method.
3. Smears are investigated by light micros<
copy with the use of immersion optic (×1.350).
More then 500 cells in several fields are regis<
tered and number of ingested particles (yeast
cells or polymer beads) in each cell is noted
(including zero). The next indexes of phagocy<
tosis are calculated: phagocytosis indices,
phagocytosis number I (extensive) and phago<
cytosis number II (intensive), defined as fol<
lows:
Phagocytosis index — percent of phago<
cyting cells in cell population;
Phagocytosis number I (extensive) —
amount of ingested particles, calculated for
all registered cells;
Phagocytosis number II (intensive) —
amount of ingested particles, calculated on
phagocytic (active) cells only.
Results and Discussion
Among a variety of methods of preparing
of functional polymeric particles, the methods
based on using SAP and OMC as universal and
convenient tool are looking to be the most
prospective for obtaining of reactive polymer<
ic particles of tailored size and functionality.
1. Water dispersion polymerization initi6
ated by OMC
Previously we have studied the formation
of primary reactive polymer nanoparticles
with functional shell by the technique of water
dispersion polymerization initiated by OMC
[8, 9]. The main regularities of controlled rad<
ical polymerization initiated by oligoperoxide
Men+<containing surfactants indicate the pos<
sibility of the obtaining polymer water disper<
sions comprising of unimodal nanoparticles
with particle size in the range 30–70 nm as
shown on Fig. 3 reactive functional shell capa<
ble to radical, condensation and other reac<
tions [9] in accordance with the scheme of
polymerization presented below (Fig. 4).
БІОТЕХНОЛОГІЯ, Т. 1, №1, 2008
90
Using coordinating oligoperoxide com<
plexes with cations of rare earth elements for
the initiation of styrene dispersion polymer<
ization provides obtaining luminescent poly<
meric nanoparticles with narrowed particle
size distribution (Fig. 5 and 6). The nanoparti<
cle luminescent properties were investigated
by professor A. Voloshinovsky.
One can see that highly monodisperse
nanoparticles can be synthesized only at opti<
mal content of luminescent OMC in water dis<
persion system as initiator and stabilizer. This
is explained, possibly, by the change of nano<
particle formation mechanism at different
OMC concentrations.
Functional polystyrene nanoparticles pos<
sess intense luminescent ability due to avail<
ability of coordinated Ce3+ cations in the func<
tional particle shell. It is evident that decrease
of nanoparticles concentration in water system
leads to the enhancement of luminescence
intensity as a result of the increase of the sys<
tem transparency.
Fig. 3. SEM picture of functional polystyrene
nanoparticles
Fig. 4. Assumed mechanism of functional polymeric
nanoparticle formation as a result of styrene water
dispersion polymerization initiated by OMC
Fig. 5. Size distribution of luminescent polymeric
nanoparticles:
1— polystyrene latex with 3% of Се3+ complex;
2 — polystyrene latex with 2% of Се3+ complex;
3 — polystyrene latex with 1% of Се3+ complex
([Ce3+] =1.25%)
Fig. 6. TEM picture of polystyrene nanoparticles
with functional shell containing coordinated Ce+3
cations:
2% of Се<oligoperoxide complex per Н2О
([Ce3+] =1.25%)
Експериментальні статті
91
As a result of sorption immobilization of
luminescent surface<active oligoperoxide
modifiers onto magnetic ferric oxide nanopar<
ticle surface the novel functional magnetic
and luminescent nanoparticles were synthe<
sized (Fig. 7).
2. Water dispersion co6polymerization with
surface6active monomers (SM and MD,
have been synthesized by dr. O. Hevus
and prof. V. Novikov respectively, Lviv
Polytechnic National University)
Novel monodisperse functional and colored
polymer water dispersions with definite particle
size and functionality were developed using sur<
face<active functional maleates (SM) and acry<
lates containing chromophore fragments (MD)
as comonomers at water dispersion emulsifier
free copolymerization of styrene. The struc<
tures of used SM are presented on the Fig 8.
It is evident from the Fig. 9 that copoly<
merization of styrene with SM and MD of
above<mentioned structures provides obtain<
ing controlled amount of highly monodisperse
colored nanoparticles with size 300 nm
depending on the content of SM in initial
monomer system.
3. Seeded polymerization initiated from the
surface of the particles modified by OMC
Functional polymeric nanoparticles con<
taining radical forming sites in oligoperoxide
shell immobilized on the particle surface are
efficient initiators of seeded polymerization
providing grafting of various functional
chains at the definite distance from the parti<
cle core. The experimental results of seeded
low temperature polymerization initiated
from the surface of functional polymer
nanoparticles presented in the Table 1 display
he formation of composite particles with
«core<shell» morphology and the possibility of
obtaining multi<layer reactive shell ws a result.
It is evident (Fig. 10) that various monomers
and monomer systems can be used for the
Fig. 7. Spectra of luminescence of coordinating
oligoperoxide Ce3+ complex, polymeric (1, 2, 3) and
hybrid magnetic (4) nanoparticles with functional
shell containing oligoperoxide Ce6complex:
1 — Water dispersions of polystyrene nanoparticles
with functional shell containing coordinated Ce3+
cations (3% of Се<oligoperoxide complex per Н2О
([Ce3+] = 1.25%, [SC] latex = 17.0%);
2 — Water dispersions of polystyrene nanoparticles
with functional shell containing coordinated Ce
cations (3% of Се<oligoperoxide complex per Н2О
([Ce3+] = 1.25%, [SC] latex = 4.25%);
3 — Water dispersions of polystyrene nanoparticles
with functional shell containing coordinated Ce
cations (3% of Се<oligoperoxide complex per Н2О
([Ce3+] = 0.03%, [SC] latex = 17.0%);
4 — Fe3O4 nanoparticles with functional shell con<
taining coordinated Ce3+ cations (Се<oligoperoxide
complex [Ce3+] = 1.25%)
Fig. 8. Structures of surface6active monomers (SM) and monomeric dyes (MD)
used for the obtaining colored polymeric nanoparticles
БІОТЕХНОЛОГІЯ, Т. 1, №1, 2008
92
fomation of the second and third functional
polymer shells on the particles resulting in the
change of particles hydrophobic<hydrophilic
properties, their functionality and enhan<
cement of size.
The dependences of seeded polymerization
rate on the concentration of sodium pentade<
cyl sulphonate and particle<initiator content
in the systems testify to the occurrence of the
polymerization exceptionally on the primary
particle surface providing the increase of
their size. No news particles are formed du<
ring seeded polymerization initiated by parti<
cles modified by OMC.
As a result of seeded water dispersion poly<
merization initiated by radical forming sites
in functional oligoperoxide shell new particles
with complicated morphology and targeted
functionality, compatibility (including bio<
compatibility) and reactivity can be synthe<
sized.
4. Homogeneous nucleation from the salt
solutions in the presence of SAP or OMC
This is the method of the formation of pri<
mary reactive inorganic particles with func<
tional shell by homogeneous nucleation from
the solutions of corresponding metal salts in
the presence of SAP and OMC [10–12] as it fol<
lows from the scheme (Fig. 11).
Reactive Ni colloids, Fe3O4, Ag and other
nanoparticles with narrowed particle size dis<
tribution and tailored functional shell and
compatibility were synthesized by this techni<
que in the presence of oligoperoxide surfac<
tants [13–17]. The number average particle
size distribution testifies to the tendency of
the formation of unimodal nanoparticles at
their formation in the presence of OMC sur<
Fig. 9. Colored polystyrene nanoparticle size
distribution in water dispersion systems synthesized
with various content of surface6active maleates:
1 — 20% of SM St;
2 — 10% of SM St;
3 — 5 % SM St
Fig. 10. Polystyrene nanoparticle size distribution
after OMC initiated (1) and seeded (2) water disper6
sion polymerization
Table 1. Multi6stage seeded (co) polymerization initiated from the particle surface (293К)
First stage Second stage* Third stage **
Latex particle
structure
Dry
residue,
%
D part.,
µm
Monomer
for the
second
shell***
Dry
residue,
%
D part.,
µm
Poly<
meri<
zation
rate,
W, %/h
Mono<
mer for
the third
shell
Dry
residue,
%
D part.,
µm
Poly<
meri<
zation
rate,
W, %/h
Core St<BA<VEP
53:32:15Shell OMC
22.0 0.015 F<MA
Si<MA
BA<GMA
90:10
27.0
25.5
28.0
0.020
0.018
0.020
7.2
9.0
10.2
–
–
–
–
–
–
–
–
–
–
–
–
Core St<BA<AA
70:25:5Shell —
OMC
23.0 0.010 VEP<BA
50:50
29.0 0.014 9.0 Si<MA 33.0 0.016 7.2
F<MA 32.2 0.016 9.0
* The formation of the second shell was initiated by residual peroxide OMC in the particle shell.
** The formation of the third shell was initiated by additional ОМC sorbed onto particle surface ( 0.5% per
monomers).
*** F<MA<2,2,3,3<tetrafluoropropyl<2<methacrylate; Si<MA — (3<trimethoxysilyl) propyl<2<methacrylate;
GMA — (2,3<epoxy propyl)<methacrylate.
Diameter, nm
Експериментальні статті
93
factant (Fig. 12). This is explained as we have
shown earlier [8–10] by the displacement of
the reaction of particle nucleation into micel<
le<like structures formed by SAP, which are
the templates determining the particle size.
TEM (Fig. 12) study of nanoparticle hydro<
sols witness the possibility of controlled syn<
thesis of nanoparticles with size in the range
5–20 nm depending the nature and content of
SAP and conditions of corresponding salt
reduction in the presence of SAP as template
and stabilizer.
SAXS technique (Table 2), TEM (Fig. 12),
SEM microscopy and magnetic measurements
testify to favor of the realization of more com<
plicated mechanism of ferric oxide formation
as a result of homogeneous nucleation in the
presence of functional oligoperoxide surfac<
tants in accordance with scheme (Fig. 13).
Proceeding from SEM and TEM microsco<
py and SAXS analysis it can be suggested that
integral Fe3O4 particles with size near 100–150 nm
comprise of magnetic mineral core containing
nanocrystals with size 8–12 nm and functional
Fig. 11. Scheme of homogeneous nucleation
of metal and metal oxide particles
with functional OMC shell
Fig. 12. Micrographs of functional hybrid nanoparticles: a — ТEM image of magnetite crystals (inset: number
average distribution of crystal size obtained from SAXS data); b — SEM image of colloidal nickel particles
Fig. 13. Synthesis and transformations of biocompatible functional nanocarriers on the basis of Fe3O4
polymeric shell providing radical reactions
initiated from the particle surface and other
polymer analogous transformations.
SAP concentration and temperature of the
synthesis are main factors defining integral
nanoparticle size as well as the size of
nanocrystals (Table 2).
TEM micrographs of magnetite nanoparti<
cles after 4 and 40 s sonification confirm compli<
cated Fe3O4 nanoparticle morphology (Fig. 14).
The availability of reactive functional
shell on the nanoparticle surface not only pro<
vides tailored rheological characteristics and
compatibility with various media but also the
possibility of the occurring of radical and
other reactions with the participation of func<
tional fragments located in the particle shell
on the definite distance from the core.
5. Seeded polymerization initiated from inor6
ganic particle surface modified by OMC
The presence of radical<forming sites on
the particle surface causes the possibility of
low temperature radical formation by diter<
tiary peroxide groups and grafting polymer
chains to surface with the formation of new
functional shell at given distance from the
surface (Fig.15 and Table 3).
One can see (Fig. 15) that seeded polymer<
ization initiated from the surface of inorganic
particles obeys the same regularities, which
are peculiar to the polymerization initiated
from the polymer particle surface, namely,
independence on the concentration of the addi<
tional emulsifier. This proves the occurrence
of graft polymerization only on the particle
surface and the impossibility of particle for<
mation in the solution. The polymerization rate
and conversion depend strongly on the modi<
fied filler nature and its content in the reac<
tion system. The study of the particles after
seeded polymerization witnesses about the
increase of their size and respectively tailored for<
mation of grafted chains containing the definite
amount of active epoxide and peroxide fragments.
БІОТЕХНОЛОГІЯ, Т. 1, №1, 2008
94
Table 2. The influence of the synthesis temperature and SAP concentration
on the characteristics of functional magnetite nanoparticles
Т, К [SAP],
%
Crystal size,
dcr, nm
Seed concen<
tration
Nsmole/l·106
SAP mole<
cule amount
per 1 seed
NSAP·103
Polymer<mineral
particle size
dN, nm* / weight
mode, %
Poly<
dispersity
index k
Seed amount
per 1 parti<
cle N·10–3
293
0 10.4±1.0 1.09 0 146±57/ 96.5 1.66 2.77
0.2 9.6±0.9 1.38 0.28 97±27 / 92.1 4.62 1.03
2 8.9±0.9 1.74 2.21 78±26 / 78.4 2.94 0.67
333
0 12.6±1.1 0.61 0 71±21 / 82.4 3.19 0.18
0.2 10.5±1.0 1.06 0.36 67±19 / 73.3 2.21 0.26
2 9.6±0.9 1.38 2.78 – – –
363
0 13.3±1.2 0.52 0 87±39 / 59.3 1.83 0.28
0.2 12.4±1.1 0.64 0.60 72±27 / 44.6 1.66 0.13
2 10.2±1.0 1.15 3.33 69±27 / 58.1 2.14 0.47
Fig. 14. TEM pictures of Fe3O4 nanoparticles after 4s (a) and 40s (b) ultrasound treatment
* Number average diameter calculated for the mode with maximum weight in particle diameter distribution plot.
a b
6. Potentials for biomedical application:
Employment of nanoparticles in study
of phagocytic activity of human blood
granulocytes
The characteristics of different particle
fractions obtained by differential centrifuga<
tion are presented in Fig. 16. The most suit<
able for application in phagocytosis studies
were dimension and homogeneity of fractions
III of styrene polymers, which were sediment<
ed at relatively high g<values. The diameter of
particles in these suspensions was in 0.7–1.5 µm
range.
Latex particles as objects of phagocytosis
were pretreated with different proteins,
which is defined as «opsonization». It is known,
that efficiency of ingestion of particles by
phagocytic cells (neutrophile granulocytes or
macrophages) depends upon the properties of
particle surface, especially upon surface pro<
teins. Substances, including proteins, which
stimulate phagocytosis are called «opsonins»
and process of coating particles with these
substances does «opsonization». The most
effective opsonins are immunoglobulins and
antibodies, that are adsorbed on particle sur<
face by different bonds (physical or chemical).
In our experiments, opsonization of
microparticles was performed by using proteins
of human blood serum, or concanavalin A. The
last one is a plant protein — lectin, which selec<
tively binds carbohydrates mannose, glucose
and acetamidoglucose. In natural conditions, it
binds with polysaccharides glucans and man<
nans, or with glycoproteins, exposing residues
of mannose and acetamidoglucose. Being
absorbed on particle surface, concanavalin A
favors the attachment of particle to cell surface
of phagocytes ant its ingestion.
Investigations of phagocytosis activity
obtained with different types of latexes are
shown in table 4.
In Fig. 17 an example of cytological pat<
tern of phagocytosis with different objects
including polymer coated nickel micro parti<
cles is presented.
Експериментальні статті
95
Fig. 15. Water dispersion polymerization rate of
VEP6GMA*6St mixture vs. filler content (1, 2) and
concentration of emulsifier E630 (1a, 2a).
Initiation from the OMC modified filler surface:
g<Fe2O3 ([OMC] = 0.7%) (1, 1a) colloidal
Ni particles ([OMC] = 0.45%) (2, 2a); 291 К
Table 3. Characteristics of copolymer GMA6VEP6St grafted to the surface of inorganic nanoparticles
(291 К; monomers: Н2О = 1:5; GMA6VEP6St 2:1:1)
Particles Particle
content,%
Content
of grafted
copolymer, %
Composition of grafted copolymer, %
GMA VEP St
γ<Fe2O3
[OMC] = 0.7%
17.4 1.6 50.0 25.0 25.0
30 2.5 60.0 19.0 21.0
60 5.0 75.0 16.0 9.0
Colloidal Ni
[OMC] = 0.45%
17.4 0.8 65.0 5.5 29.5
30 1.1 55.0 6.0 39.0
60 2.5 50.0 10.0 40.0
* Glycidil methacrylate.
БІОТЕХНОЛОГІЯ, Т. 1, №1, 2008
96
Fig. 16. Fractions of nanoparticles obtained with centrifugation of latex at different g6values:
1 — sediment, obtained by spontaneous sedimentation (1g) for two hours;
2 — fraction, obtained by centrifugation at 540 g for 15 min;
3 — fraction, obtained by centrifugation at 2.000 g for 15 min;
4 — fraction, obtained by centrifugation at 3.300 g for 25 min
Table 4. Effectiveness of polystyrene latexes as objects of phagocytosis
N Object of phagocytosis Phagocytosis
index (%)
Phagocytosis
number I
(extensive)
Phagocytosis
number II
(intensive)
1 Yeast cells Debariomyces hansenii 40 0.65 1.6
2 Unsensibilized latex #1 18 0.2 1.3
3 Latex #1 43 1.2 2.7
4 Latex #1, sensibilized with proteins of human blood serum 50 1.5 3.0
5 Latex #3, sensibilized with concanavalin A 34 0.9 2.7
6 Latex #3, sensibilized with proteins of human blood serum 45 1.0 2.4
7 Latex NM<20, sensibilized with concanavalin A 21 0.3 1.3
8 Latex NM<20, sensibilized with proteins of human blood
serum 17 0.2 1.1
9 Latex #11, sensibilized with concanavalin A 47 0.9 1.9
10 Latex #11, sensibilized with proteins of human blood serum 65 1.9 2.9
11 Latex Viola<1 (LV<1), sensibilized with concanavalin A 40 0.9 2.4
12 Latex Viola<2 (LV<2), sensibilized with concanavalin A 47 0.9 2.4
13 Latex Viola<3 (LV<3), sensibilized with concanavalin A 50 1.0 2.0
In this research various approaches of
oligoperoxide metal complexes and surface<active
oligoperoxides use for the activation of colloidal
particles causing polymer grafting onto their sur<
face have been demonstrated. They permit to
obtain nanoparticles of «core<shell» structure
with fragments providing their tailored compati<
bility, functionality and reactivity including bio<
compatibility and specific biological activity.
Functional nanoparticles including magnet<
ic, colored and luminescent ones contain the
spacers with the functional groups, which are
capable to radical and polymer<analogous trans<
formations. They were successfully tested as
stained or magnetic labels for investigation of
phagocytosis, labeling of pathological cells as
well as nanocarriers for addressed drug delivery.
In phagocytosis experiments, the advantage
of latex microparticles as compared with yeast
cells is the existence of chemically conditioned
surface and possibility of its modification by
attachment of distinct ligand with known
Експериментальні статті
97
Fig. 17. Activity of polymorphonuclear leukocytes with different objects of phagocytosis:
1, 2 — phagocytosis of commonly used object — yeast cells Deberiomyces hansenii.
1 — in the central part four moderately active neutrophiles (1–2 yeast cells ingested) are visible, in upper part
(12 o’clock) nonphagocyting eosinophile (common state), in the left part of image (7 o’clock) — active monocyte;
2 — the group of hyperreactive neutrophiles, the cytoplasm is completely occupied with ingested yeasts;
3, 4, 5 — particles of latex NM<20 as objects of phagocytosis;
3 — opsonization with proteins of human blood serum, two silent and one weak activity neutrophiles are present,
on periphery there are three silent (non<phagocytic) lymphocytes (common state);
4 — opsonization with proteins of human blood serum, the group of hyperreactive neutrophiles;
5 — opsonization with concanavalin A; in the left side hyperreactive neutrophiles are visible, in the right side —
two silent neutrophiles;
6 — nickel particles coated with polymeric envelope as an object of phagocytosis
structure. The surface of yeast cells is very
complex and manifold, dependent from the
strain of microorganism. Due to this considera<
tion, the interpretation of results obtained with
using microparticles is much easier.
Efficiency of ingestion of latex particles
by phagocytes depends from chemical nature
of polymer, technology of production, opsoni<
zation. Opsonization with proteins of blood
serum or with lectins (in our case with con<
canavalin A) significantly increases the effi<
ciency of their ingestion by phagocytes and
achieves values for classical object of phagocy<
tosis — yeast cells.
Nickel microparticles coated with polymer
envelope and opsonized with blood serum pro<
teins are comparatively well ingested by
phagocytes and can be used for isolation of
phagocyting cells from the rest of population
using magnet, as particles possess ferromag<
netic properties.
Proposed technology of synthesis of latexes
and their fractionation for obtaining a mono<
disperse suspensions can be used for determi<
nation of phagocytosis activity of blood cells in
clinical laboratories with diagnostic purpose.
The study described in the article was
obtained during performance of two STCU
projects (#1930 and 4140). The authors
express their thanks to Professor A. Voloshi<
novssky for his fruitful discussion of experi<
mental results.
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НОВІ ФУНКЦІОНАЛЬНІ НАНОРОЗМІРНІ
КОМПОЗИТИ НА ОСНОВІ
ОЛІГОПЕРОКСИДНИХ СУРФАКТАНТІВ:
СИНТЕЗ І ЗАСТОСУВАННЯ В БІОЛОГІЇ ТА
МЕДИЦИНІ
О. C. Заіченко1, Р. С. Стойка2, Н. Є. Мітіна1,
М. Д. Луцик2, О. М. Шевчук1, В. Р. Лобаз1,
Н. М. Бойко2
1Національний університет «Львівська
політехніка», Львів
2Інститут біології клітини НАН України,
Львів
E$mail: zaichenk@polynet.lviv.ua
Розглянуто основні експериментальні
підходи до цілеспрямованого синтезу поверх<
нево<активних олігопероксидних речовин і їх
застосування з метою одержання полімерних
і гібридних нанорозмірних носіїв, яким при<
таманна скерована функціональність та біосу<
місність. Конструювання нових лінійних, бло<
кових та гребенеподібних олігопероксидних
сурфактантів, а також їхніх похідних коорди<
наційних комплексів із катіонами перехідних
та рідкоземельних металів є зручним інстру<
ментом для синтезу люмінесцентних, магніт<
них та інших функціональних нанокомпозитів
із регульованим розподілом за розмірами, функ<
ціональністю, реактивністю та біосумісністю.
Розроблені методи дозволяють поєднати ста<
дію формування полімерних, металевих та
металооксидних наночастинок зі стадією нео<
боротної модифікації їхньої поверхні функціо<
нальними поверхнево<активними олігоперок<
сидами, здатними зв’язувати фізіологічно
активні речовини. Наявність реакційноздат<
них дитретинних пероксидних фрагментів
уможливлює функціоналізацію створених на<
ночастинок, що їх було застосовано для дослі<
дження фагоцитозу як поверхневі маркери па<
тологічних клітин, а також для спрямованого
доставлення лікарських препаратів.
Ключові слова: олігопероксидні сурфактанти,
металеві комплекси, радикальна емульсійна полі<
меризація, гомогенна нуклеація, функціональні
колоїдні частинки, затравкова полімеризація,
фагоцитоз, доставлення лікарських препаратів.
НОВЫЕ ФУНКЦИОНАЛЬНЫЕ НАНО6
РАЗМЕРНЫЕ КОМПОЗИТЫ НА ОСНОВЕ
ОЛИГОПЕРОКСИДНЫХ СУРФАКТАНТОВ:
СИНТЕЗ И ПРИМЕНЕНИЕ В БИОЛОГИИ
И МЕДИЦИНЕ
О. С. Заиченко1, Р. С. Стойка2,
Н. Е. Митина1, М. Д. Луцик2,
О. М. Шевчук1, В. Р. Лобаз1, Н. М. Бойко2
1Национальный университет «Львовская
политехника», Львов
2Институт биологии клетки НАН Ук$
раины, Львов
E$mail: zaichenk@polynet.lviv.ua
Рассмотрены основные эксперименталь<
ные подходы к целенаправленному синтезу
олигопероксидных поверхностно<активных
веществ и их использованию для получения
полимерных и гибридных наноразмерных но<
сителей, обладающих заданной функциональ<
ностью и биосовместимостью. Конструирование
новых линейных, блочных и гребеневидных
олигопероксидных сурфактантов, а также их
производных координационных комплексов
с катионами переходных и редкоземельных
металлов является удобным инструментом
для синтеза люминесцентных, магнитных
и других функциональных нанокомпозитов
с регулируемым распределением по размеру,
функциональности, реакционной способности
и биосовместимости. Разработанные методы
обеспечивают совмещение стадии формирова<
ния полимерных, металлических и металло<
оксидных наночастиц со стадией необратимой
модификации их поверхности функциональ<
ными поверхностно<активными олигоперокси<
дами, способными к связыванию физиологически
активных веществ. Наличие реакционноспо<
собных дитретичных пероксидных фрагмен<
тов обеспечивает возможность функционали<
зации полученных наночастиц, которые
использовались для изучения фагоцитоза как
поверхностные маркеры патологических кле<
ток, а также для целевой доставки лекарствен<
ных препаратов.
Ключевые слова: олигопероксидные сурфак<
танты, металлические комплексы, радикальная
эмульсионная полимеризация, гомогенная нуклеа<
ция, функциональные коллоидные частицы, затра<
вочная полимеризация, фагоцитоз, доставка лекар<
ственных препаратов.
Експериментальні статті
99
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>>
>> setdistillerparams
<<
/HWResolution [2400 2400]
/PageSize [612.000 792.000]
>> setpagedevice
|