Design and Development of Surface Modification and Synthesis Strategies to Reduce Toxicity of Nanoparticles

Transcription

1 Design and Development of Surface Modification and Synthesis Strategies to Reduce Toxicity of Nanoparticles Seda Keleştemur Genetics and Bioengineering Department Yeditepe University Istanbul, Turkey

2 Outline Determination surface modifiers and surface modification strategies Surface modification process and characterization of the nanoparticles Toxicity assesment Conclusions

3 Determination of The Best Surface Chemistry The selection and design of the surface modifiers by considering Nontoxicity Stability Biocompatibility Cost and availability Compatibility with the physicochemical properties of the NMs and chemistry,

4 Silver Nanoparticles (AgNPs) Surface Modification Strategies Zinc oxide Nanoparticles (ZnO NPs) Quantum Dots (QDs)

5 Modification of AgNPs with thiolated carbohydrates and biomolecules Selected Surface Modifiers; Lactose Starch Oligonucleotide Folic acid AgNPs synthesized in Yeditepe University AgNPs obtained from PlasmaChem

6 Characterization of AgNPs with thiolated carbohydrates and biomolecules

7 % Cell Viability % Cell Viability % Cell Viability % Cell Viability Cytotoxicity of modified AgNPs HDF Cells HDF Cells HDF Cells HDF Cells control 12, AgNPs (PC) (µg/ml) Bare Lactose Starch ODN FA control AgNPs (YU) (µg/ml) Bare Lactose Starch ODN 120 A549 Cells A549 Cells 120 A549 Cells A549 Cells Bare Lactose Starch ODN FA Bare Lactose Starch ODN 0 control AgNPs (PC) (µg/ml) 0 Control AgNPs (YU) (µg/ml)

8 A Safety by Design Approach for AgNPs Modification the Lee and Meisel Method by varying; The reaction time The reducing agent concentration

9 Characterization of AgNPs synthesized by varying reaction time UV-Vis and DLS spectra of AgNPs prepared with increasing reaction time from 5 min to 50 min.

10 Characterization of AgNPs synthesized by varying reaction time

11 Characterization of AgNPs synthesized by varying citrate concentration UV-Vis and DLS spectra of AgNPs prepared at different citrate concentrations.

12 Characterization of AgNPs synthesized by varying citrate concentration

13 Cytotoxicity of AgNPs synthesized by varying reaction time and their supernatants HDF Cells HDF Cells A549 Cells A549 Cells

14 Cytotoxicity of AgNPs synthesized by varying citrate concentration and their supernatants HDF Cells HDF Cells A549 Cells A549 Cells

15 Surface Modification Strategies for ZnO NPs Hydroxylation Process Bare ZnO Hydroxylated ZnO Silica Coating Process

16 Bovine serum albumin (BSA) attachment onto silica coated ZnO NPs

17 Amine terminated poly(ethylene glycol) (PEG-NH 2 ) 2 attachment onto silica coated ZnO NPs

18 Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) attachment onto silica coated ZnO NPs

19 Poly(lactide-co-glycolide) (PLGA) attachment onto silica coated ZnO NPs

20 % Cell Viability % Cell Viability Cytotoxicity of Modified ZnO NPs 200 HDF Cells 200 A549 Cells Bare 120 Bare 80 BSA PHB 80 BSA PHB 40 0 control PEG PLGA 40 0 control PEG PLGA ZnO NPs (µg/ml) ZnO NPs (µg/ml)

21 Quantum Dots (QDs) QD-Si-OH QD-Si(2)-NH 2 QD-Si(4)-NH 2

22 Initial Characterization of QDs

23 Glucose Modification of QDs-Si-OH

24 % Cell Viability % Cell Viability QDs-Si-OH-Glucose Cytotoxicity Assessments 150 HDF Cells QD-OH QD-OH-Glucose 150 A549 Cells QD-OH QD-OH-Glucose control Concentration (µg/ml) 0 control Concentration (µg/ml)

25 Overall Conclusions AgNPs All attempts to reduce the toxicity with surface modifications were failed while the citrate reduced AgNPs synthesized through Lee and Meisel method were nontoxic. The few nanometers of AgNP seeds were the main source of toxicity in a AgNP colloidal suspension. Surface modification may increase lifetime of the AgNPs in the media by decreasing the dissolution of the AgNPs. ZnO NPs The initial characterization of the modified ZnO NPs suggests that all surface modifications are successful. Both polymers and BSA modifications hepled to decrease cellular toxicity according to pristine ZnO NPs. The most important outcome is the surface modifications must be performed in extremely diluted suspensions by using excess amount of modifier to cover the whole surface area of ZnO NPs. QDs It is necessary to coat the surface of QDs with a silica layer to prevent the Cd ion release into the medium. The strategy of glucose modification helped to reduce the cytotoxicity without altering the fluorescence properties of QDs.

26 NANOBIOTECHNOLOGY Nanobiotechnology and AND Molecular MOLECULAR Engineering ENGINEERING Group GROUP From left to right: Melis Emanet, Cansu Umran Tas, Pinar Akkus, Seda Keleştemur, Mine Altunbek, Zehra Yilmaz, Mustafa Çulha, Özlem Şen, Manolya Hatipoglu, Esen Efeoglu, Emine Kazanç, Emre Cebeci, Sevda Mert, Sinan Sabuncu, Ibrahim Can Sevim, Saban Kalay, Ertug Avcı