Laboratory "Polymers for biology"

Department of Biomaterials and Bionanotechnology

Head: Vitaly Zubov, D.Sc, professor
zubov@ibch.ru+7(495)335-10-11

polymer-containing nanocomposites and nanomaterials, adsorbent, bioseparation, biocatalysts, fluorescent polymer particles, semiconductor nanocrystals, latex particles, microencapsulation of tumor cells, biodegradable polymer systems for drug delivery, microencapsulated DNA vaccines, controlled drug release, encapsulated peptides, biomaterials for tissue engineering

The Laboratory is engaged in development of composite adsorbents for bioseparation, model membranes based of monolayers and liposomes, immune dispersion diagnostic test-systems, biocompatible systems for enzyme and cell encapsulation and  systems for hybridizational analysis.

Development of novel polymer and polymercontaining composite nanomaterials based on porous and non-porous matrices for bioseparation and bioanalysis, and biocompatible nanocoatings (including techniques for modification of the implant properties). The work in under supervision of Dr. D. Kapustin and Dr. A. Generalova:

  • Development of direct synthesis of nanocomposites having detailed characterized morphology (Fig. 1), providing the localization of the polymerization process at the surface layers of matrices and introducing of additional functional groups (incliding bioligands) into obtaining materials;
  • Development of universal adsorbents based on disperse carriers, capillaries, membranes, monoliters, silica chips, etc) modified with fluoropolymers and/or polyanilines, for one-step isolation and purification of biopolymers (nucleic acids, proteins, peptides) (Fig. 2).  The obtained materials are perspective for elaboration of kits and protocols providing effective diagnostics of human pathogens, in particular, using PCR, and they also effective as supports for mass-spectrometry.;
  • Development of the universal heterogeneous initiators of polymerization based on inorganic supports treated with ozone, for preparation of composite adsorbents modified with  the polymers of different chemical nature;
  • Design of biocatalists based on composite matrices modified with smart-polymers with immobilized bioligands (enzymes), which are effective both in the aqueous and in organic media (Fig. 3);
  • Development of biocompatible matrices based on natural and synthetic polymers for obtaining biodegradable implants (in particular, intravascular stents); 
  • Elaboration of synthesis methods of colored and fluorescent polyacrolein and copolymer microspheres to obtain new bioanalitical reagnets for nigh-sensitive express-analysis of proteins, haptens and nucleic acids;
  • Preparation of composite copolymer microspheres containing the fluorescent CdSe/ZnS nanocrystals close to surface. Such morphology makes it possible to register the fluorescence changing due to insignificant changing of environment, such as pH, ionic strength, temperature, etc, and use them as optical sensors (Fig. 4). 

 

Risunok1.jpg

Fig. 1. Morphology of conposition adsorbents.

 

Risunok1.jpg

Fig. 2. One-step biopolymers isolation.

 

Risunok1.jpg

Fig. 3. Enzime activity of lipase immobilized on silica.

 

Risunok1.jpg

Fig. 4. Inclusion of fluorescent CdSe / ZnS nanocrystals in polymer microspheres and their application in bioassay.

The Laboratory cooperates with the laboratories of the Institute, as well as with the Central Clinical Hospital, the University of Kent (United Kingdom), the"Agrobiogen" consortium (Germany), the "Charite" clinic (Germany), etc.

A decision to organize Polymers for biology laboratory was made in 1979 as a result of several discussions of Prof. V.P. Zubov and the director of the Institute of Chemistry of the Natural Compounds academician Yu.A. Ovchinnikov at symposiums and conferences. During these meetings they discussed an important role of chemistry of materials for the development of biology and medicine, a strong dependence of this scientific field on imported reagents and materials as well as a lack of specific departments for developing new materials for biology and biotechnology in our country.

  • So, the necessity to have high-purified concentrated samples of biologically active substances, in particular, biopolymers (such as nucleic acids and proteins) resulted in development of a number of effective sorption composite materials (adsorbents) combining the superior mechanical merits of solid insoluble matrix with unique sorption properties of polymer modifiers (primarily fluoropolymers and polyanilines). As it known, the most synthetic polymer materials are not suitable for use as “good” adsorbents due to certain properties (e.g. swelling ability, softness, low solubility or contrariwise, instability). Therefore, from practical point of view, use of polymer modifiers to obtain the composite materials seems to be an optimal way.  
  •  A number of conditions were considered when technologies of such adsorbents preparation were developed.  
  •  First, to provide defect-free morphology of obtained materials the principal of localization of polymerization process at surface layers of the support was adapted. For this purpose several approaches were developed to provide an activation of the carrier surface via different physical-chemical methods including radiolysis of the silica support surface, modification of the carrier surface with low-molecular or high-molecular agents, activation of the surface with ozone, usage of microwave or ultrasound treatment, etc.   
  • Consequently, high-effective biocompatible (i.e. excluding an irreversible denaturation of biopolymers) chromatographic materials were obtained.  These materials were characterized with chemical stability, low non-specific sorption, high selectivity under biopolymers separation conditions. The examples of such developed in the laboratory materials are adsorbents  based on porous silica modified with polytetrafluoroethylene, polytrifluorostyrene, poly-p-nitrophenylacryate, polyaniline and their derivatives. 
  •  Secondly, the modern trends to miniaturization, robotization and reduction of time expenditures in the analytical tests as well as in the realization of preparative tasks, have required to develop simpler and cheaper (as compared to traditional column chromatographic systems and devices for solid-phase extraction) instruments for bioseparation and sample-preparation. Therefore, effective protocols of isolation and purification of biopolymers based on use of compact cartridges containing 60 – 100 mg of adsorbent were developed. Unique sorption properties of polymer modifiers in a content of the developed composites allowed to realizing of the conception based on one-step separation of nucleic acids and proteins. In this case, nucleic acid passes through the cartridge in excluded volume, but proteins, peptides and concomitant impurities are retained by the adsorbent. Moreother, the same sorption material can be used to separate the components of the retained protein fraction, if necessary.
  •  The examples of practical use of this principal are protocols of DNA isolation from the lysates of bacterial cultures, plant tissues, blood, etc. The obtained purified samples of DNA are suitable for direct use in PCR-analysis. The most effective materials for this aim are adsorbents based on porous silica and synthetic membranes modified with polyaniline and copolymers of aniline with 3-aminobenzoic acid.  Such materials were successfully used for express sample-preparation followed by PCR-diagnostic of hepatitis C virus, as well as a number of bacterial and fungal urogenital infections.
  •  The functional properties of the described materials make them perspective for use in automated bioseparation systems both in the genomic and in the proteomic areas. However, these applications do not limit the fields of use of developed materials. Introducing of the additional functional groups into polyaniline modifiers provides to obtain new effective biocompatible materials, for example, the supports for bioanalytical application. New effective bioanalytical system based on silica support for mass-spectrometry was developed and patented (jointly with Royal Philips Electronics). The system exploits the ability of polyaniline-containing coating to separate the proteins (peptides) depending on pI value of individual component, as well as its ability to accumulate the laser energy.
  •  Developed methods were successfully used to obtain effective biocatalists based on silica modified with thermal-sensitive copolymer of N-vinylcaprolactame with 2-hydroxiethylmetacrylate. Lypase from Pseudomonas fluorescence was immobilized on the surface of obtained polymer-coated material. Thus obtained biocatalyst demonstrated higher enzymatic activity as compared to native lipase samples. Enzymatic activity in this case was kept both in aqueous and organic media.
  •  Introducing of the additional functionality to fluoropolymers also widens the fields of them applications. Use of partially fluorinated polymers to modify the supports provides not only improvement of their wettability, but also makes it possible to immobilize different bioligands. Method of preparation of stable fluoropolymer-containing support for solid-phase synthesis of oligonucleotides was developed in the laboratory. This method is based on preliminary modification of porous silica with fluoropolymer having active ester groups. After specific chemical modification using nucleozide, the obtained stable material was successfully used as a support for solid-phase synthesis of oligonucleotides.
  •  A versatility of fluoropolymer- and polyaniline-modified composite materials appears not only in wideness of their use for resolution of different chromatographic and diagnostic tasks, but also from technological point of view, so as the features of their chemical structure and properties allow to preparation of the composites effectively combining the properties of both polymer modifiers in the same material. To confirm the above, one can exemplify new technique developed in the laboratory “Polymers for biology”. The technique is based on use of silica matrices treated with ozone, which thus posturize the multi-purpose heterogenic initiators capable effectively initiate polymerization of such chemically different compounds as fluoropolymers and aniline.     
  •  Advantages of use of the composite materials with nanostructural elements also were realized in producing of bioanalytical systems based on polymer particles containing various (fluorescent, chromophoric) labels. The methods of preparation of dispersions containing polymer particles based on polyacrolein were used to produce a number of labeled bioanalytical reagents for latex-agglutination reaction performing to determine different analytes, such as diphtherin, ferritin, herbicides (2,4-D, atrazine, simazine), antibodies to lipopolysaccarides containing in the cytoderm of opportunistic pathogenic bacteria, thyroglobulin, thyroid body peroxidase, antibodies to  mycobacteria of tuberculosis, etc.The work was carried out together with a wide range of scientific organizations (Mechnikov Research Institute of Vaccines and Sera, Russian Academy of Medical Sciences; Research and development center “Medical immunology”; Helmholtz Research Institute of Eye Diseases, etc).
  •  Recently semiconductive nanocrystals CdSe/ZnS (so called quantum dots – QDs) attract attention as perspective fluorophores. A panel of colloidal-stable polymer fluorescent particles of different diameter (0.15 – 0.52 mkm) was prepared by introducing of QDs into preliminary synthesized particles based on copolymers of acrolein with styrene. The obtained particles conjugated with monoclonal antibodies to Yersinia pestis antigen, and then the particles were used in reaction of passive agglutination both in the tests using glass slides (express-analysis) and in the simplest and most sensitive semiquantitative immunoanalytical variant using plates.   
  •  An example of conjugates of fluorescent polymer particle with antibodies 4D5scFv demonstrates the possibility to in vitro label specifically the receptor HER2/neu at the membrane surface in the cells of human ovarian adenocarcinoma SKOV-3. The work was carried out in collaboration with the laboratories of Molecular biophysics and Molecular immunology of IBCh RAS.
  •  A number of international and Russian patents were registered, in which the most of above developments (in particular, fluoropolymer- and polyaniline-containing adsorbents for one-step DNA isolation, bioseparating elements for sample-preparation in PCR-analysis, silica chips modified with copolymers of aniline for SELDI-TOF-MS analysis, etc) were described. 
NamePositionContacts
Vitaly Zubov, D.Sc, professordepart. dir.zubov@ibch.ru+7(495)335-10-11
Alla Generalova, Ph.D.s. r. f.a-generalova@yandex.ru+7(495)336-06-00
Dmitry Kapustin, Ph.D.s. r. f.kapustin@ibch.ru+7(495)336-06-00
Elena Yagudaeva, Ph.D.s. r. f.elena-yagudaeva@yandex.ru+7(495)330-67-65, +7(495)336-06-00
Svetlana Sizova, Ph.D.r. f.sv.sizova@gmail.com+7(495)336-06-00
Aleksandr Vikhrov, Ph.D.r. f.+7(495)330-06-00
Larisa Zhigis, Ph.D.r. f.zhigis@ibch.ru+7(495)330-67-65
Vera Zueva, Ph.D.r. f.itsvera@maiI.ru+7(495)330-67-65
Anna Prostyakova, Ph.D.r. f.profan@list.ru+7(495)336-06-00
Anastasia GilevaPhD stud.sumina.anastasia@mail.ru
Ol'ga Razguljaevares. eng.+7(495)336-06-00

Former members:

Elena Markvicheva, D.Scl. r. f.lemark@ibch.ru
Oksana Selina, Ph.D.j. r. f.oselina@inbox.ru
Daria Zaytseva-Zotova, Ph.D.j. r. f.Dariaz.z@gmail.com
Maria DrozdovaPhD stud.drozdovamg@gmail.com
Roman AkasovPhD stud.roman.akasov@gmail.com
Anna KhovankinaPhD stud.khovankina@gmail.com

Selected publications

  1. Liaw , Yagudaeva , Prostyakova , Lazov , Zybin , Ischenko , Zubov , Kapustin  (2016). Sorption behavior of polyaramides in relation to isolation of nucleic acids and proteins. Colloids and Surfaces B: Biointerfaces 145, 912–921 [+]

    The effect of chemical composition and morphology of the surface layers of new polyaramide-containing sorbents on the mechanism of selective sorption of nucleic acids and proteins was investigated as compared to the previously studied sorbents modified with fluoropolymers and polyaniline (high-throughput materials providing one-step isolation of DNA from biological mixtures).The observed sorption behavior was shown to be determined by the chemical structure and not by the morphology of the polymer coating. It was proposed that similarity of the sorption properties of the series of chemically different polymers could be determined by similar total input of different sorption mechanisms.

    ID:1621
  2. Zhigis L.S., Kotelnikova O.V., Vikhrov A.A., Zinchenko A.A., Serova O.V., Zueva V.S., Razgulyaeva O.A., Gordeeva E.A., Melikhova T.D., Nokel E.A., Alliluev A.P., Drozhzhina E.Y., Rumsh L.D. (2015). A new methodological approach to estimation of IgA1 and IgA2 content in human serum using recombinant IgA1 protease from Neisseria meningitidis. Biotechnol. Lett. 37 (11), 2289–93 [+]

    A new approach to estimation of IgA subclass levels and IgA1/IgA2 ratio using enzymatically active and inactive forms of Neisseria meningitidis IgA1 protease was developed.

    ID:1429
  3. Zinchenko A.A., Alliluev A.P., Serova O.P., Gordeeva E.A., Zhigis L.S., Zueva V.S., Razgulyaeva O.A., Melikhova T.D., Nokel E.A., Drozhzhina E.Y.u., Kotelnikova O.V., Rumsh L.D. (2015). Immunogenic and protective properties recombinant proteins based on meningococcal IgA1 protease. J Meningitis 1 (102), [+]

    Recombinant proteins (M1K2–N963-LEH6, MA28–N963-LEH6 and ME135–H328-LEH6) have been created on the basis of the genome sequence of IgA1 protease of N. meningitidis serogroup B strain H44/76. It is revealed that, similarly to the native enzyme isolated earlier from N. meningitidis serogroup A strain A208, these proteins induce formation of animal protection against the infection with the virulent strain of meningococcus serogroup B. It is shown that these compounds are promising as a basis for a polyvalent anti-meningococcal vaccine.

    ID:1428
  4. Generalova A.N., Kochneva I.K., Khaydukov E.V., Semchishen V.A., Guller A.E., Nechaev A.V., Shekhter A.B., Zubov V.P., Zvyagin A.V., Deyev S.M. (2015). Submicron polyacrolein particles in situ embedded with upconversion nanoparticles for bioassay. Nanoscale 7 (5), 1709–17 [+]

    We report a new surface modification approach of upconversion nanoparticles (UCNPs) structured as inorganic hosts NaYF4 codoped with Yb(3+) and Er(3+) based on their encapsulation in a two-stage process of precipitation polymerization of acrolein under alkaline conditions in the presence of UCNPs. The use of tetramethylammonium hydroxide both as an initiator of acrolein polymerization and as an agent for UCNP hydrophilization made it possible to increase the polyacrolein yield up to 90%. This approach enabled the facile, lossless embedment of UCNPs into the polymer particles suitable for bioassay. These particles are readily dispersible in aqueous and physiological buffers, exhibiting excellent photoluminescence properties, chemical stability, and also allow the control of particle diameters. The feasibility of the as-produced photoluminescent polymer particles mean-sized 260 nm for in vivo optical whole-animal imaging was also demonstrated using a home-built epi-luminescence imaging system.

    ID:1431
  5. Guller A.E., Generalova A.N., Petersen E.V., Nechaev A.V., Trusova I.A., Landyshev N.N., Nadort A., Grebenik E.A., Deyev S.M., Shekhter A.B., Zvyagin A.V. (2015). Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells. Nano Research 8 (5), 1546–1562 [+]

    The cytotoxicity and non-specific cellular uptake of the most popular composition of upconversion nanoparticle (UCNP), NaYF4:Yb3+:Er3+, is reported using normal human skin cells, including dermal fibroblasts and immortalized human epidermal linear keratinocytes (HaCaT). A new hydrophilization reaction of as-synthesized UCNPs based on tetramethylammonium hydroxide (TMAH) enabled evaluation of the intrinsic cytotoxicity of bare UCNPs. The cytotoxicity effects of the UCNP surface-coating and polystyrene host were investigated over the concentration range 62.5–125 μg/mL with 24-h incubation, using a MTT test and optical microscopy. The fibroblast viability was not compromised by UCNPs, whereas the viability of keratinocytes varied from 52% ± 4% to 100% ± 10% than the control group, depending on the surface modification. Bare UCNPs reduced the keratinocyte viability to 76% ± 3%, while exhibiting profound non-specific cellular uptake. Hydrophilic poly(D,L-lactide)- and poly(maleic anhydride-alt-1-octadecene)-coated UCNPs were found to be least cytotoxic among the polymer-coated UCNPs, and were readily internalized by human skin cells. Polystyrene microbeads impregnated with UCNPs remained nontoxic. Surprisingly, no correlation was found between UCNP cytotoxicity and the internalization level in cells, although the latter ranged broadly from 0.03% to 59%, benchmarked against 100% uptake level of TMAH-UCNPs.

    https://static-content.springer.com/image/art%3A10.1007%2Fs12274-014-0641-6/MediaObjects/12274_2014_641_Fig1_HTML.gif
    ID:1430
  6. Kapustin D.V., Prostyakova A.I., Zubov V.P. (2014). Fluoroplast-polyaniline-coated adsorbent for one-step isolation of DNA for PCR detection of viral hepatitides (HBV and TTV). Bioanalysis 6 (7), 957–66 [+]

    To demonstrate the effectiveness of application of the adsorbent successively modified with nano-layers of fluoroplast and polyaniline for one-step isolation of DNA of hepatitis B virus and transfusion-transmitted virus from human serum.

    ID:1423
  7. Kapustin D.V., Prostyakova A.I., Alexeev Y.I., Varlamov D.A., Zubov V.P., Zavriev S.K. (2014). High-throughput Method of One-Step DNA Isolation for PCR Diagnostics of Mycobacterium tuberculosis. Acta Naturae 6 (2), 48–52 [+]

    The efficiency of one-step and multi-step protocols of DNA isolation from lysed sputum samples containing the Mycobacterium tuberculosis complex has been compared. DNA was isolated using spin-cartridges containing a special silica-based sorbent modified with fluoroplast and polyaniline, or using an automated isolation system. One-step isolation using the obtained sorbent has been shown to ensure a significantly lower DNA loss and higher sensitivity in the PCR detection of Mycobacterium tuberculosis as compared to a system based on sorption and desorption of nucleic acids during the isolation.

    ID:1424
  8. Ягудаева Е.Ю., Жигис Л.С., Разгуляева О.А., Зуева В.С., Мельников Э.Э., Зубов В.П., Козлов Л.В., Бичучер А.М., Котельникова О.В., Аллилуев А.П., Аваков А.Э., Румш Л.Д. (2010). Выделение и определение активности IGA1-протеиназы из культуры Neisseria meningitidis. Биоорг. хим. 36 (1), 96–105 [+]

    A method of the isolation and purification of IgA1 protease from a culture of Neisseria meningitidis serogroup A has been developed. It was shown that IgA1 protease isolated from serogroup A meningococcus is capable of protecting experimental animals (mice) infected with meningococcus of serogroup B.

    ID:209
  9. Ягудаева Е.Ю., Букина Я.А., Простякова А.И., Зубов В.П., Тверской В.А., Капустин Д.В. (2009). Окислительная полимеризация анилина на поверхности кремнезема в присутствии полисульфокислот как способ получения эффективных биосорбентов. Высокомолекулярные соединения 51 (6), 1000–1007 [+]

    Polyaniline coatings on the surface of the macroporous silica have been prepared by oxidative polymerization via protonation of aniline by poly(sulfonic acids): poly(p,p'_(2,2'_disulfonic acid)diphenyleneisophthalamide (iso-PSA) and poly(p,p'_(2,2'_disulfonic acid)diphenyleneterephthalamide (tere-PSA).

    ID:211
  10. Zubov V.P., Kapustin D.V., Generalova A.N., Yagudaeva E.Y.u., Vikhrov A.A., Sizova S.V., Muidinov M.R. (2007). Modification of solids with polymer nanolayers as a process for manufacture of novel biomaterial. POLYMER SCIENCE SERIES A 49 (12), 1247–1264 [+]

    The results of study on the chemical deposition of polymeric coatings of a nanoscale thickness on porous and flat inorganic matrices and encapsulation of nano-and microparticles in polymer shells are discussed. Procedures for the deposition of homogeneous defect-free coatings are detailed by using polytetrafluoroethylene, polyaniline, and their derivatives as examples. The matrices modified with nanosized polytetrafluoroethylene and polyaniline layers are promising biomaterials for one-step isolation of nucleic acids from complex biological mixtures (cell and tissue lysates, whole blood, plant feedstock), as well as for high-performance chromatography of proteins and other biopolymers. Approaches to the fabrication of polymer shells on luminescent nanocrystals of (CdSe)ZnS via the inclusion of the nanocrystals in micrometer-sized particles based on acrolein-styrene copolymers and the formation of polymer shells directly on nanoparticles are discussed. It was shown that polymer-functionalized luminescent nanocrystals hold promise as bioanalytical reagents.

    ID:127
  11. Kapustin D.V., Vikhrov A.A., Gorokhova I.V., Generalova A.N., Kalyazina O.V., Murzabekova T.V., Zubov V.P. (2005). Multicomponent thermosensitive systems for biocatalysts. RUSSIAN CHEMICAL BULLETIN 54 (2), 452–457 [+]

    Composite matrices based on macroporous silica modified by N-vinylcaprolactam copolymers with diallyldimethylammonium chloride and with 2-hydroxyethyl methacrylate were obtained. Lipase from Pseudomonas fluorescens was immobilized on the obtained materials. The temperature dependence of the hydrolytic activity of the immobilized lipase preparations in the triacetin hydrolysis was investigated. The hydrolytic activity of lipase immobilized on the matrix modified by the N-vinylcaprolactam copolymer with 2-hydroxyethyl methacrylate can be regulated by varying the temperature of the reaction medium. The temperature dependence of the hydrolytic activity of the immobilized enzyme has a maximum at 40 °C, the activity of the immobilized lipase being ∼3.5 times higher compared to that at 20 °C. After immobilization on these composite materials, lipase retained the activity in the acetylation of 1-(RS)-phenylethanol with vinyl acetate in ButOMe.

    ID:128
  12. Капустин Д.В., Ягудаева Е.Ю., Завада Л.Л., Жигис Л.С., Зубов В.П., Ярошевская Е.М., Плобнер Л., Лайзер Р.-.М., Брем Г. (2003). Композиционный полианилинсодержащий кремнеземный сорбент для выделения ДНК. Биоорг. хим. , 310–315 [+]

    A composite sorbent based on porous glass beads modified with thin polyaniline coating was prepared by precipitation aniline polymerization in the presence of carrier surface. It was shown that the modification ensures the uniform coating of the inner surface of the carrier pores with the polymer layer~1nm thick. It was shown that the resulting material retains the initial porosity of the carrier and is selective in the separation of nucleic acids and proteins. The polyaniline-coated sorbents were shown to be efficient for the preparative DNA isolation from bacterial lysates.

    ID:210

Vitaly Zubov

  • Russia, Moscow, Ul. Miklukho-Maklaya 16/10 — On the map
  • IBCh RAS, build. 34, office. 431
  • Phone: +7(495)335-10-11
  • E-mail: zubov@ibch.ru

The multichannel tip for extraction of nucleic acids, proteins and peptides. (2016-03-17)

A method of modifying the inner surface of the glass multi capillaries (MC) with nano layers of polyaniline, and a method of the manufactured MC-containing tips for mechanical dispensers utilization in DNA extraction procedure from blood for subsequent PCR-analysis were elaborated. According to experts from FGIH Russian Research Anti-Plague Institute "Microbe" the developed systems have been effective in the sample preparation procedure relating to DNA isolation from blood samples, in particular, to detect the strains of Vibrio cholerae and Yersinia pseudotuberculosis.

Jointly with the RDE “Nanostructured Glass Technology", Saratov, Russia, the RF Patent No 2547597 from 12.03.2015 (Skibina Y.S., Beloglazov V.I., Tuchin V.V., Kapustin D.V., Prostyakova A.I. "Multichannel tip for extraction of nucleic acids, proteins and peptides") was obtained.

The composite material for radiopaque visualization radio non-opaque implants. (2016-03-17)

As a part of R&D (Step 2) under the Agreement between the IBCh RAS and LLC “BIOSTEN” No 08.01.2014 from 28.08.2014 [in pursuance of to the Agreement with the Fund "Skolkovo" grant No 18 from 28 June 2011, assigned in the framework of the Innovation project "Development of multi purpose endovascular implants (stents) with the properties of biodegradation"] a new biocompatible and biodegradable polymer glycolan-containing coatings on the surface of the polymeric biodegradable vascular stents, as well as methods of administration of glycolan into the volume of the stent material were developed. Due to optimized conditions of glycolan inclusion, it provides satisfactory radiopacity not only during the stenting procedure, but also after the installation, and at the same time it provides an additional positive effect by virtue of the therapeutic properties of glycolan.

Submicron polyacrolein particles in situ embedded with upconversion nanoparticles for bioassay (2016-03-17)

We report a new surface modification approach of upconversion nanoparticles (UCNPs) structured as an inorganic host NaYF4 codoped with Yb3+ and Er3+ based on their encapsulation at a two-stage process of precipitation polymerization of acrolein under alkaline conditions in the presence of UCNPs. The use of tetramethylammonium hydroxide both as an initiator of the acrolein polymerization and agent for the UCNP hydrophilization made it possible to increase the polyacrolein yield up to 90%. This approach enabled facile, lossless embedment of UCNPs into the polymer particles suitable for bioassay. These particles are readily dispersible in aqueous and physiological buffers, exhibiting excellent photoluminescent properties, chemical stability, and allowed control of the particle diameters. The feasibility of as-produced photoluminescent polymer particles mean-sized 260 nm for in vivo optical whole-animal imaging was also demonstrated using a home-built epi-luminescence imaging system.

Publications

  1. Generalova A.N., Kochneva I.K., Khaydukov E.V., Semchishen V.A., Guller A.E., Nechaev A.V., Shekhter A.B., Zubov V.P., Zvyagin A.V., Deyev S.M. (2015). Submicron polyacrolein particles in situ embedded with upconversion nanoparticles for bioassay. Nanoscale 7 (5), 1709–17 [+]

    We report a new surface modification approach of upconversion nanoparticles (UCNPs) structured as inorganic hosts NaYF4 codoped with Yb(3+) and Er(3+) based on their encapsulation in a two-stage process of precipitation polymerization of acrolein under alkaline conditions in the presence of UCNPs. The use of tetramethylammonium hydroxide both as an initiator of acrolein polymerization and as an agent for UCNP hydrophilization made it possible to increase the polyacrolein yield up to 90%. This approach enabled the facile, lossless embedment of UCNPs into the polymer particles suitable for bioassay. These particles are readily dispersible in aqueous and physiological buffers, exhibiting excellent photoluminescence properties, chemical stability, and also allow the control of particle diameters. The feasibility of the as-produced photoluminescent polymer particles mean-sized 260 nm for in vivo optical whole-animal imaging was also demonstrated using a home-built epi-luminescence imaging system.

    ID:1431
  2. Guller A.E., Generalova A.N., Petersen E.V., Nechaev A.V., Trusova I.A., Landyshev N.N., Nadort A., Grebenik E.A., Deyev S.M., Shekhter A.B., Zvyagin A.V. (2015). Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells. Nano Research 8 (5), 1546–1562 [+]

    The cytotoxicity and non-specific cellular uptake of the most popular composition of upconversion nanoparticle (UCNP), NaYF4:Yb3+:Er3+, is reported using normal human skin cells, including dermal fibroblasts and immortalized human epidermal linear keratinocytes (HaCaT). A new hydrophilization reaction of as-synthesized UCNPs based on tetramethylammonium hydroxide (TMAH) enabled evaluation of the intrinsic cytotoxicity of bare UCNPs. The cytotoxicity effects of the UCNP surface-coating and polystyrene host were investigated over the concentration range 62.5–125 μg/mL with 24-h incubation, using a MTT test and optical microscopy. The fibroblast viability was not compromised by UCNPs, whereas the viability of keratinocytes varied from 52% ± 4% to 100% ± 10% than the control group, depending on the surface modification. Bare UCNPs reduced the keratinocyte viability to 76% ± 3%, while exhibiting profound non-specific cellular uptake. Hydrophilic poly(D,L-lactide)- and poly(maleic anhydride-alt-1-octadecene)-coated UCNPs were found to be least cytotoxic among the polymer-coated UCNPs, and were readily internalized by human skin cells. Polystyrene microbeads impregnated with UCNPs remained nontoxic. Surprisingly, no correlation was found between UCNP cytotoxicity and the internalization level in cells, although the latter ranged broadly from 0.03% to 59%, benchmarked against 100% uptake level of TMAH-UCNPs.

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