Molecular Understanding, Design, and Development of Ultra Low Fouling Zwitterionic-based Functional Materials

Transcription

1 Molecular Understanding, Design, and Development of Ultra Low Fouling Zwitterionic-based Functional Materials Shaoyi Jiang Boeing-Roundhill Professor Departments of Chemical Engineering & Bioengineering University of Washington, Seattle Santa Rosa, CA ctober 11, 2013

2 utline I. Introduction Nonfouling mechanism & design principle II. Surface Coatings Graft-from/graft-to & fully switchable IIII. Hydrogels Tissues, bloods and cells IV. Nanoparticles Protein, micelle, liposome and solid NPs

3 Biofouling Control Controlling unwanted interactions is critical for many applications Medical Devices Pharmaceuticals Consumers Engineering Kaparissides, et al., Azojono, Poly(ethylene glycol) Subject to oxidation Amphiphilic PEG Less effective in complex media Harder for direct functionalization Protein or microorganisms Nonfouling Surfaces Substrates

4 Design Principles Hydrogen-bonding Hydration by PEG (Bridging Water) Langmuir, 20, 8931 (2004). Nonfouling + Crystal Hydration is the key Flexibility helps, but not required Crystal Design Criteria Hydration (primary) Flexibility (secondary) Langmuir, 22, 8186 (2006). H-bonding Neutral & hydrophilic (PEG and Sugar) H H H H H Ionic Zwitterionic (Lipids, MPC, proteins, CB, SB ) P - N + S. Chen, J. Zheng, L. Li, and S. Jiang, Journal of the American Chemical Society, 127, (2005).

5 Existing Materials Poly(ethylene Glycol) (PEG) n (CH 2 CH 2 )nh Phosphobetaine (PC) HN Lipid n Unstable P Bzl N HN Hard to synthesize Ultra Low Fouling Zwitterionic Materials Z NH Zwitterionic Sulfobetaine (SB) n H H n N N H mn n R H H R NH 2 TFA/HBr Polymerization N taurine N S Carboxybetaine (CB) glycine betaine Bzl Biomimetic NH Ultra low fouling Z Deprotection K, E-NCA KE Mixed Peptide KE Mixed Peptide (Protected) (Deprotected) Functionalizable Superhydrophilic Switchable Mixed Charge Mixed charge MA * H N C mn H m N Peptide NCA NH 3 n H N n All natural S. Jiang and Z. Cao, Advanced Materials. 22, 920 (2010) R

6 E and K Dominate Protein Surfaces Analysis of 1400 Proteins E K Blood < cytoplasma < chaperon A. White and S. Jiang, Chemical Sciences, 3, 3488 (2012)

7 utline I. Introduction Nonfouling mechanism & design principle II. Surface Coatings Graft-from/graft-to & fully switchable IIII. Hydrogels Tissues, bloods and cells IV. Nanoparticles Protein, micelle, liposome and solid NPs

8 Thickness & Density Ultra Low Fouling Surface Coatings Graft-from-surface Surface packing density is the key ATRP RAFT Controlled Photo pcb Graft-to-surface Thiol/silane Hydrophobic Hydrophilic DPA Complex biological media (a) Blood compatibility (undiluted human blood plasma/serum, whole blood & in vivo blood circulation) (b) Tissue compatibility (in vivo subcutaneous implantation) (c) Matured biofilms and spores

9 PCB is also functionalizable De-activation leads to a zwitterionic nonfouling background nly PCB has this unique capability H. Vaisocherová, et al., Analytical Chem., 80, 7894 (2008).

10 Surface Coating Examples Creating protein arrays on a single PCB material Dip-coating CB-DPA polymer conjugate onto Fe34* * Also applied to Au, silica, QD Passivating and functionalizing microfluidic/pdms channels No coating/ fouling Coating/ nonfouling No Bacterial/Biofilm on coated glass slides P. Aeruginosa untreated treated 10

11 Switchable from Antimicribial to Nonfouling a b Hydrolysable pcbma-1 C2 Kill Release c d Cationic pc8nma e f Hydrolysable Cationic Zwitterionic Zwitterionic pcbma-2 Catching, Killing and Release Angewandte Chemie, 47, 8831 (2008). Highlighted by Science, 322, 651 (2008) Highlighted by Nature Materials, 7, 834 (2008).

12 Fully Switchable between Antimicribial and Nonfouling Water Weak Acid Advantages Repeated switching Mild hydrolysis condition 100 Killing 3.5x10 Release Resistance 6 3.0x10 6 7x10 6 Live Bacteria / % < 99.9% < 99.9% CB-Ring CB-H C8N CB-Ring CB-H N+ Bacterial Density / cells cm x x x x x CB-Ring CB-H C8N C8N After Release Before Release Bacterial Density / cells cm -2 6x10 6 5x10 6 4x10 6 3x10 6 2x10 6 1x CB-Ring CB-H C8N Z. Q. Cao, et al., Angewandte Chemie, 50, 6102 (2011). Z. Q. Cao, et al. Angewandte Chemie, 124, 2656 (2012).

13 utline I. Introduction Nonfouling mechanism & design principle II. Surface Coatings Graft-from/graft-to & fully switchable IIII. Hydrogels Tissues, bloods and cells IV. Nanoparticles Protein, micelle, liposome and solid NPs

14 pcb Hydrogel from CB monomer and CB Crosslinker CB1 monomer Non-functionalizable CB2 monomer Functionalizable CBX1 crosslinker Non-functionalizable CBX2 crosslinker Functionalizable Extremely low fouling and high mechanical properties L. R. Carr, H. Xue, and S. Jiang, Biomaterials, 32, 961 (2010). L. R. Carr, Y. Zhou, J. E. Krause, H. Xue, and S. Jiang, Biomaterials, 32, 6893 (2011). L. R. Carr, J. E. Krause, J. R. Ella-Menye, and S. Jiang, Biomaterials, 32, 8456 (2011).

15 Implantable PCB Hydrogels Low Capsule No capsule for Subcutaneous implantation in mice for 3 months phema pcb In collaboration with Buddy Ratner Nature Biotechnology, 31, 553, 2013

16 Pro-inflammatory Anti-inflammatory (PHEMA) (PCB) Nature Biotechnology, 31, 553, 2013

17 pcb Hydrogel for Glucose Sensors in Whole Blood Stability (> 42 vs. 1.5 days) Commercial sensor This work Paper Strip W. Yang, L.R. Carr, T, Bai, A, J. Keefe, J. Xu, H, Xue, C. Irvin, S. Chen, J. Wang, S. Jiang, Biomaterials, 33, 7945 (2012).

18 pcb Nanogels for Longer Circulation and Lower Splenic Accumulation Blood Circulation Bio-distribution Correlation L. Zhang, Z. Cao, Y. Li, J.R. Ella-Menye, T. Bai, and S. Jiang, ACS Nano, 6, 6681 (2012).

19 utline I. Introduction Nonfouling mechanism & design principle II. Surface Coatings Graft-from/graft-to & fully switchable IIII. Hydrogels Tissues, bloods and cells IV. Nanoparticles Protein, micelle, liposome and solid NPs

20 PCB-conjugated Proteins - Maintaining Stability & Bioactivity Protein PEGylation Amphiphilic Stability Bioactivity Zwitterionic Superhydrophilic Stability Bioactivity A.J. Keef, S.Y. Jiang, Nature Chemistry, 4, 59 (2012)

21 pcb-protein Conjugate: Stability and Bioactivity Stability Bioactivity PEG pcb

22 PCB-PLGA Micelles for Drug Delivery - Sharp Hydrophobic/hydrophilic Contrast PCB-PLGA PEG-PLGA oil water Sharp Interface PCB or PEG (hydrated shell) PLGA (hydrophobic core) Mutual Solubility NP suspended After lyophilization N sucrose NP Size (nm) ± ±0.052 PDI= 0.212± ± ± ±0.017 PLGA PLGA-PCB PLGA-PCB/Dtxl 1wt % Drug Loading High-speed centrifuge Lyophilization without cryoprotectant Re-suspension without sonication Z. Q. Cao, Q. Yu, H. Xue, G. Cheng and S. Jiang, Angew. Chem. Int. Ed., 49, 3771 (2010).

23 Marine Coatings Anti-fouling (AF) coatings TBT, Cu or biocides Ban of TBT in 2008 Fouling-release (FR) coatings Silicone-based or fluorinated-based polymers Effective on vessels moving at higher speeds A global environmental and energy issue Green Alga Barnacles Environmentally benign, durable, effective, and low-cost Ultra Low Fouling or Nonfouling (NF) Coatings Spray Coatings Marine Lab Test Field Test in San Diego Aluminum Panels Spray coating PDMSE Glass Zwitter

24 Acknowledgements Jiang Research Group (August 2012)

25 Acknowledgements ffice of Naval Research (NR) (Environment, Biology, and Chemistry) National Science Foundation (NSF) (DMR, CERT, and CMMI) Defense Threat Reduction Agency (DTRA) Army Research ffice (AR) Defense Advanced Research Projects Agency (DARPA) Boeing-Roundhill Professor