Nanoimprint lithography based fabrication of shape-specific, enzymatically-triggered smart nanoparticles.
Our ability to precisely manipulate size, shape and composition of nanoscale carriers is essential for controlling their in-vivo transport, bio-distribution and drug release mechanism. Shape-specific, "smart" nanoparticles that deliver drugs or imaging agents to target tissues primarily in response to disease-specific or physiological signals could significantly improve therapeutic care of complex diseases. Current methods in nanoparticle synthesis do not allow such simultaneous control over particle size, shape and environmentally-triggered drug release, especially at the sub 100 nm range. We report here a high-throughput nanofabrication technique using synthetic and biological macromers (peptides) to produce highly monodisperse, enzymatically-triggered nanoparticles of precise sizes and shapes. Particles as small as 50 nm were fabricated on silicon wafers and harvested directly into aqueous buffers using a biocompatible, one-step release technique. We further demonstrate successful encapsulation and precisely controlled enzyme-triggered release of antibodies and nucleic acids from these nanoparticles, thus providing a potential means for disease-controlled delivery of biomolecules.
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
Luz Cristal
LC
Glangchai
Mary
M
Caldorera-Moore
Li
L
Shi
Krishnendu
K
Roy
D000906:Antibodies / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry; D002021:Buffers; D002401:Cathepsin B / Q000032:analysis / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D004798:Enzymes / Q000494:pharmacology*; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes / Q000378:metabolism; D020100:Hydrogels / Q000378:metabolism; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000295:instrumentation / Q000379:methods*; D009930:Organic Chemicals / Q000378:metabolism; D010316:Particle Size; D010957:Plasmids; D011092:Polyethylene Glycols / Q000737:chemistry; D012825:Silicon / Q000737:chemistry; D019809:Streptavidin / Q000378:metabolism; D013499:Surface Properties; D013997:Time Factors; D014867:Water / Q000737:chemistry
D000906:Antibodies; D001672:Biocompatible Materials; D002021:Buffers; D004337:Drug Carriers; D004798:Enzymes; D005456:Fluorescent Dyes; D020100:Hydrogels; D009930:Organic Chemicals; C099476:PicoGreen; D014867:Water; D011092:Polyethylene Glycols; D004247:DNA; D019809:Streptavidin; D002401:Cathepsin B; C013411:biocytin; D008239:Lysine; D012825:Silicon