Interfacing Nanoparticles to Biology Kimberly Hamad-Schifferli - PowerPoint PPT Presentation

Interfacing Nanoparticles to Biology Kimberly Hamad-Schifferli Biological and Mechanical Engineering, MIT Understanding and Synthesis of nanoparticles with Nanoscale interfaces manipulation of particle unique properties with proteins and heating DNA f 1 f 2 f + H 3 N NH 3 + S S + H 3 N S + Triggering drug release N H Multifunctional particles S 3 S + H N S S 3 NH 3 * + H 3 N S * + * * N * * H 3 + * * * *

Nanoscale Interfaces to Biology red blood cell diatom ~5 µ m (SEM) 30 µ m Simple DNA proteins molecules nm <1nm bacteria 1 µ m m 10 -10 10 -9 10 -8 10 -7 10 -6 10 -5 10 -4 10 -3 10 -2 SOI transistor width 0.12 µ m semiconductor Circuit design nanocrystal (CdSe) Copper wiring Nanometer memory element width 0.2 µ m 5nm IBM PowerPC 750 10 12 bits/cm 2 (1Tbit/cm 2 ) Microprocessor 7.56mm × 8.799m 6.35 × 10 6 transistors �

Controlling Biology with Nanoparticles Exploit physical properties of inorganic nanoparticles Making an interface that •Heating by fields preserves biological function •Fluorescence + Magnetic (quantify) Target function of biological molecules and processes •Multifunctional particles •Drug Delivery •Imaging •Gene expression

Enhancing Antisense Gene Regulation with NPs • Use NPs to enhance antisense by steric blockage • Study conformation of DNA on NP protein ribosome + AUG mRNA protein protein antisense strand ribosome antisense strand (DNA 15-20mer) ~20nm with NP AUG AUG no protein no protein ~7nm NP with DNA 14mers S. Park, K. A. Brown, K. Hamad-Schifferli, Nano Lett ., 2004 S. Park and K. Hamad-Schifferli, J. Phys. Chem. C , 2008 K. A. Brown, S. Park, K. Hamad-Schifferli, J. Phys. Chem. C , 2008

Characterizing NP-protein Interfaces Labeling site Sites sensitive to protein stability? NP ligand positive/negative/neutral improve/worsen protein folding? MD simulations (Wonmuk Hwang, TAMU) NP material molecular interactions Different affinity for different residues? NP size effect of curvature on protein folding? M.-E. Aubin, D. G. Morales, K. Hamad-Schifferli., Nano Lett. , 2005 M.-E. Aubin-Tam and K. Hamad-Schifferli., Langmuir , 2005 M.-E. Aubin-Tam, H. Zhou, K. Hamad-Schifferli., Soft Matter , 2008 M.-E. Aubin-Tam and K. Hamad-Schifferli, Biomed Mater , 2008

Nanoparticles as multifunctional therapeutic agents Carrier for drugs • Inefficient conjugation • Large Imaging (multimodal) • Stability and biocompatibility * * * * * targeting Au 8 -PAMAM particles: Polyamidoamine dendrimer • Delivery • Functionalizable Au 8 : T 1 T 2 •Fluorescence Untreated •MRI 60nM ~3nm 120nM