Nanoparticles for biomedical imaging and biomolecular transport and manipulation.

摘要

Optical imaging has emerged as a valuable tool to visualize and study biological processes in living subjects. Semiconductors quantum dots (QDs), the current gold standard for nanoparticle imaging, have achieved indisputable success in this regard. However, due to the presence of heavy metal components, they exhibit significant toxicity in the biological environment, which limits their use in vivo.;This thesis introduces nanocomposites made of carbon dots (C-dots) encapsulated in poly(lactic-co-glycolic acid) (PLGA) carriers as potential imaging agents for in vivo applications. C-dots (~ 1 nm in diameter) were synthesized from commercially available carbon black precursors to allow high volume production of these particles. They were subsequently encapsulated in biodegradable PLGA nanospheres to prevent rapid renal clearance, which affects nanoparticles smaller than 6 nm in diameter. Toxicity of both C-dots and C-dot-PLGA nanocomposites was evaluated using HepG2 liver cell lines. C-dots displayed significantly less toxicological responses than QDs and therefore could be considered as promising agents for in vivo imaging.;Because of their unique physicochemical properties, nanoparticles have not been limited to imaging applications. Rather, their potentialities have been extended to the control and manipulation of matter at the nanoscale. In addition, the ongoing quest for powerful and versatile nano-tools has lead to the development of multifunctional nanocomposites that allow parallel imaging and manipulation of biomolecules. Going a step further, researchers have designed nanoplatforms where engineering and biological principles interplay for the execution of multiple functions.;This thesis describes micellar nanocomposites in which QDs and superparamagnetic iron oxide nanoparticles (SPIONs) are encapsulated. Interfaced with a magnetic manipulation platform and with a kinesin-microtubule cellular transport system, these nanocomposites permitted simultaneous imaging, transport and manipulation of proteins (e.g. avidin). Finally, our work lays down preliminary characterization studies related to dual functional nanocomposites made of fluorescent nanodiamonds (NDs) and SPIONs encapsulated in PLGA carriers. These nanocomposites may carry both imaging and therapeutic capabilities and thus might be used for theranostic applications.