Sailor Smrt Dst

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Smart Dust: Nanostructured

microcarriers for drug delivery

Michael J. Sailor, Ph.D. Professor, UCSD Department of

Chemistry and Biochemistry [email protected]

William R. Freeman, M.D., Ph.D. Professor, UCSDDepartment of Ophthalmology

Lingyun Cheng, M.D.Assistant Project Scientist, UCSD

Department of Ophthalmology

Erkki Ruoslahti, M.D., Ph.D., The Burnham InstituteSangeeta N. Bhatia, M.D., Ph.D. Associate Professor, MIT

Department of Bioengineering


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2 technologies for controlled drug delivery to the eyeUnidirectional episcleral plaques use a nanostructured template to

prepare a polymeric material that can be sewn onto the back of the

eye. The plaque has a designed nanostructure that can be used tocontrol the rate of release of the drug.

Encoded microparticles use a

nanoporous Si or SiO2 material.

Methods to load, seal, and trigger

release of small molecule, peptide, or

protein-based drugs have been

developed.

nanotemplated

polymer

porous Si

master

composite

PLA

sclerananoporousmembranereservoirbacking

eyeinterior

Above: Photonic color

code changes when

particle releases payload.

Right: Porous Si micro-particles in the rabbit eye.


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Smart Dust photonic crystal particlesMichael J. Sailor, UCSD

Design a mother ship nanostructure to

carry and release a cargo or perform adiagnostic test

Build a code

Load a drug

Target the nanostructure to a desired

location

Monitor the nanostructure in-vivo

Ophthalmoscope image of porous Si photonic

crystals (green color) in the intravitreal region of

the rabbit eye. These particles are the size of the

diameter of a human hair. CourtesyWilliam R.

Freeman, M.D. and Lingyun Cheng, M.D., ShileyEye Center, University of California, San Diego

Smart Dust


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Porous Silicon Synthesis

Electron microscopeimage of porous Si.

Side view of porous Sielectrochemicallyetched into a single

crystal Si wafer.

Background:Properties of Porous Silicon; Canham, L.,Ed.; EMIS Datareviews, INSPEC: London, 1997; Vol. 18.

2Si + 6 HF + 2 h+

Si

H

Porous Si Surface

+ H2SiF6+ 2H

++ 1/2 H2

20 m


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Pore size is controlled electrochemically

Current Density for samples at right:

(A) 1.5 x 1.5 mm, 150 mA/cm

2

(B) 5 x 5 mm, 295 mA/cm2

(C) 5 x 5 mm2, 370 mA/cm2

(D) 5 x 5 mm2, 440 mA/cm2

(E) 5 x 5 mm, 515 mA/cm2

(F) 5 x 5 mm2, 600 mA/cm2

Depends on:

Current densityHF concentrationElectrolyte composition (usually

ethanol, but other organic solvents

have been used)

Dopant type, and dopantconcentration


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Range of Accessible Pore Sizes

1 0 0 0 n m = 1 m

1 0 0 n m

P o r o u s S i l i c o n P o r e S i z eB i o l o g i c a l M o l e c u

R e d b l o o d c e l l s

M i t o c h o n d r i a

H u m a n s e r u m a l b u m i n

D N A


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Photonic Crystals-color from a nanostructure

PARKER, A. R., et.al., J. Exper. Biol. 1998201, 1307-

1313.

Calloodes grayanus Porous Si multilayer

1

m

2 mm


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Berger, M. G.,et al., Thin Sol. Films1997, 297, 237-240Meade, S. O.;et al.Adv. Mater.2004, 16, 1811-1814.

Encoding strategy


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Complicated codes can be placed on a particle


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Microdroplet patterningto produce a composite photonic crystal

Li, Y. Y.; Kollengode, V. S.; Sailor, M. J.Adv. Mater.2005, in press.

silicon porousSiphotoniccrystal

etchspraypolymer

NaOH(aq)

250C30min

400 500 600 700 800 900 1000

Reflected

intensity(rel)

Wavelength (nm)

0 hr

1 hr

2 hr

3 hr

4 hr

5 hr

with polymerbare

Can encapsulate drugs,

attach targeting moieties


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Opening pores to load a drug

HF/DMSO

30 min

Dexamethasone

Langmuir2004, 20, 11264-11269.


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Chemistry can change rate of release of

dexamethasone from porous Si

0

20

40

60

80

100

120

0 1 2 3 4 5 6 7 8

%D

rugReleased

Time (hours)

Fresh

Hydrosilylated

H-terminated material

completely releases

dexamethasone after 2 hours,

corresponding to complete

dissolution of the porous Si

layer. After 7 hours only 50-60% of the drug is released

from the more stable

hydrosilylated material. After

an initial 2-hour burst, these

hydrosilylated samplessteadily released drug for a

period of 3 days.

Langmuir2004, 20, 11264-11269.


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Electropolished PSi Polymer-PSi Composite

Etching conditions : p++ Type Si wafer, HF:EtOH = 3:1 solution

100 mA/1.3 cm2 ~ 250 mA/1.3 cm2

2 sec intervals; 50 repeats

Electropolishing conditions: HF:EtOH = 1:14 solution

22 mA/1.3 cm2

2 min

In situ polymer. hydrolysis

Polymer-based

Photonic film

Polymer imprints from 1-D photonic crystals

Li, Y. Y. et al. Science299, 2045-2047 (2003).


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Porous Si/polynorbornene composite film held between

two pairs of tweezers, showing the mechanical stability of

the materials

Flexible 1-D photonic crystals

Yoon, et. al. Chem. Commun.2003, 680-68.

RingOpeningMetathesisPolymerization

PorousSi Template

Si

Si

Composite

400 500 600 700 800 900 1000

Relative

Intensity

Wavelength (nm)

Fresh Porous Si

Composite


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Monitoring drug delivery with a biocompatible

polymeric photonic crystal

0

0.01

0.02

0.03

0.04

0.05

0.06

10 100 1000

1100

1200

1300

1400

1500

1600

1700

Relativerugatep

eakintensity

Caffeine

abs

orbanceinsolution

Time, min

Measurement of degradation of polylactide rugate peak as a

surrogate for the delivery of caffeine (pH=10, aqueous)Li, et. al.

Science,2003 (299)2045-2047.


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Chemical Sensing with a Si Photonic Crystal

400 450500 550600 650700 750800

Wavelength(nm)

Si-R

R-Si

Si-R

R-Si

+A


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Targeted Microcarriers


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Silicon Porous Si Mirror Modified Porous Si

Double MirrorFreestandingPorous Si

Smart Dust

Etch Hydrosilylate

Etch

Release,oxidize

Sonicatehydrophilic

hydrophobic

hydrophobic

Self-orienting, self-targeting smart

dust particles

1-dodecene

J.R. Link and M.J. Sailor, Proc. Nat. Acad. Sci.2003, 100, 10607-10610.


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Encoded particles self-assemble on a target

oxidized

alkylated

Hydrophobic

Hydrophilic

Proc. Nat. Acad. Sci.2003, 100, 10607-10610.

S ti S t D t


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Superparamagnetic Smart Dust

Dorvee, J. R.; Derfus, A. M.; Bhatia, S. N.; Sailor, M. J. Nature Mater.2004, 3, 896-899.

silicon porousSiphotoniccrystal

modifiedporousSi

2-sidedphotoniccrystal

magneticamphiphilicparticles

Etch

1-dodecene

Etch

Release

Sonicate

alkylated

120C

InfuseFe3O4


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Smart dust chaperonesfor liquid droplets

500 600 700 800 900

ReflectedIntensity(rel)

Wavelength, nm

I

-

(aq)

Ag+

(aq)

AgI(s)

Spectral barcodes:

Nature Mater.2004, 3, 896-899.


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Porous photonic crystals with optical barcodes can be made that allow in-

vivo monitoring

Chemistry and electrochemistry allow control of loading, degradation, andrelease rates

Porous materials can be used as templates to produce biomaterials with

controlled pore size, porosity, and optical properties Preliminary animal studies show no irritation, toxic effects Targeting can be achieved by incorporation of magnetic domains or

homing molecules

Summary

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