Micelles of Different Morphologies - Advantages of Worm-like Filomicelles of PEO-PCL in Paclitaxel Delivery

Worm-like and spherical micelles are both prepared here from the same amphiphilic diblock copolymer, poly(ethylene oxide)-b-poly (ε-caprolactone) (PEO [5 kDa]-PCL [6.5 kDa]) in order to compare loading and delivery of hydrophobic drugs. Worm-like micelles of this degradable copolymer are nanometers in cross-section and spontaneously assemble to stable lengths of microns, resembling filoviruses in some respects and thus suggesting the moniker filomicelles . The highly flexible worm-like micelles can also be sonicated to generate kinetically stable spherical micelles composed of the same copolymer. The fission process exploits the finding that the PCL cores are fluid, rather than glassy or crystalline, and core-loading of the hydrophobic anticancer drug delivery, paclitaxel (TAX) shows that the worm-like micelles load and solubilize twice as much drug as spherical micelles. In cytotoxicity tests that compare to the clinically prevalent solubilizer, Cremophor® EL, both micellar carriers are far less toxic, and both types of TAX-loaded micelles also show 5-fold greater anticancer activity on A549 human lung cancer cells. PEO-PCL based worm-like filomicelles appear to be promising pharmaceutical nanocarriers with improved solubilization efficiency and comparable stability to spherical micelles, as well as better safety and efficacy in vitro compared to the prevalent Cremophor® EL TAX formulation

Diblock copolymer worms and vesicles: Bilayer-antimicrobial interaction, electric field manipulation and glassiness

Amphiphilic diblock copolymers form various self-assembled structures in water. Of particular interest to the biophysics and bioengineering community are the vesicle morphology, which mimics the shell of biological cells, and the cylindrical worm micelle morphology, that mimics the cytoskeleton and various biofilaments in the body. This thesis explores an aspect of biological relevance of copolymer membranes, as well as develops tools and methodologies for engineering worm micelles that would enable their applicability as bio-scaffolds and stiffness tunable high aspect-ratio colloidal systems. Copolymer membranes are used as model systems to study the interaction of antimicrobial peptides with uncharged, thick, single component bilayer membranes. It is found that certain antimicrobial peptides indeed lyse polymer vesicles whose bilayers are many times the peptide length. A thorough study of the mechanism of this interaction is presented and a possible mechanism of interaction is proposed. A novel and elegant method to visualize the worm micelles as they are manipulated by an external electric field is also presented in this thesis. Finally, a new class of glassy, hinged cylindrical micelles is introduced, and it is characterized for its applicability as a stable, stiffness controllable, and shape controllable colloidal system. The rheological property of dense networks of these glassy worms is also explored, and interesting phenomenon arising from the unique structure of these worms is presented

Diblock copolymer worms and vesicles: Bilayer-antimicrobial interaction, electric field manipulation and glassiness

Amphiphilic diblock copolymers form various self-assembled structures in water. Of particular interest to the biophysics and bioengineering community are the vesicle morphology, which mimics the shell of biological cells, and the cylindrical worm micelle morphology, that mimics the cytoskeleton and various biofilaments in the body. This thesis explores an aspect of biological relevance of copolymer membranes, as well as develops tools and methodologies for engineering worm micelles that would enable their applicability as bio-scaffolds and stiffness tunable high aspect-ratio colloidal systems. Copolymer membranes are used as model systems to study the interaction of antimicrobial peptides with uncharged, thick, single component bilayer membranes. It is found that certain antimicrobial peptides indeed lyse polymer vesicles whose bilayers are many times the peptide length. A thorough study of the mechanism of this interaction is presented and a possible mechanism of interaction is proposed. A novel and elegant method to visualize the worm micelles as they are manipulated by an external electric field is also presented in this thesis. Finally, a new class of glassy, hinged cylindrical micelles is introduced, and it is characterized for its applicability as a stable, stiffness controllable, and shape controllable colloidal system. The rheological property of dense networks of these glassy worms is also explored, and interesting phenomenon arising from the unique structure of these worms is presented

Plasmonic Sensor Could Enable Label-Free DNA Sequencing

We demonstrated a proof-of-principle concept of a label-free platform that enables nucleic acid sequencing by binding methodology. The system utilizes gold surfaces having high fidelity plasmonic nanohole arrays which are very sensitive to minute changes of local refractive indices. Our novel surface chemistry approach ensures accurate identification of correct bases at individual positions along a targeted DNA sequence on the gold surface. Binding of the correct base on the gold sensing surface triggers strong spectral variations within the nanohole optical response, which provides a high signal-to-noise ratio and accurate sequence data. Integrating our label-free sequencing platform with a lens-free imaging-based device, we reliably determined targeted DNA sequences by monitoring the changes within the plasmonic diffraction images. Consequently, this new label-free surface chemistry technique, integrated with plasmonic lens-free imaging platform, will enable monitoring multiple biomolecular binding events, which could initiate new avenues for high-throughput nucleic acid sequencing