PhD Candidate, University of Connecticut
A new one-pot low-cost self-assembled lipid nanodiscs invented for cancer theranostics.
We have designed a universal platform made up of a combination of lipid molecules, which self-assembles automatically and can encapsulate, carry and deliver almost any type of cancer drug or imaging agent into the tumors' location inside the body. We have proved that it is feasible to modify the shape of the carrier and by trying different shapes, sizes, surface charges and chemistry, it has been show by our data that one of our nanoparticles, which is a discoidal lipid nanoparticle has the highest success for targeting the tumor and delivering the therapy/diagnosis agents into it. We are now translating this technology into oral drug delivery and injection administration in animal study level.
Abstract: Understanding the interaction of live cells with macromolecules is crucial for designing efficient therapies. Considering the functional heterogeneity found in cancer cells, real-time single cell analysis is necessary to characterize responses. In this study, we have designed and fabricated a microfluidic channel with patterned micromagnets which can temporarily immobilize the cells during analysis and release them after measurements. The microchannel is composed of plain coverslip top and bottom panels to facilitate easy microscopic observation and undisturbed application of analytes to the cells. Cells labeled with functionalized magnetic beads were immobilized in the device with an efficiency of 90.8±3.6%. Since the micromagnets are made of soft magnetic material (Ni), they released cells when external magnetic field was turned off from the channel. This allows the reuse of the channel for a new sample. As a model drug analysis, the immobilized breast cancer cells (MCF7) were exposed to fluorescent lipid nanoparticles and association and dissociation were measured through fluorescence analysis. Two concentrations of nanoparticles, 0.06 µg/ml and 0.08 µg/ml were tested and time lapse images were recorded and analyzed. The microfluidic device was able to provide a microenvironment for sample analysis, making it an efficient platform for real-time analysis.
Pub.: 02 Nov '16, Pinned: 29 Jun '17
Abstract: Poly(amino acid)-coated gold nanoparticles hold promise in biomedical applications, particularly because they combine the unique physicochemical properties of the gold core, excellent biocompatibility, and easy functionalization of the poly(amino acid)-capping shell. Here we report a novel method for the preparation of robust hybrid core–shell nanosystems consisting of a Au144 cluster and a densely grafted polylysine layer. Linear polylysine chains were grown by direct N-carboxyanhydride (NCA) polymerization onto ligands capping the gold nanocluster. The density of the polylysine chains and the thickness of the polymer layer strongly depend on the amount and concentration of the NCA monomer and the initiator. The optical spectra of the so-obtained core–shell nanosystems show a strong surface plasmon resonance (SPR)-like band at 531 nm. In fact, despite maintenance of the gold cluster size and the absence of interparticle aggregation, the polylysine-capped clusters behave as if they have a diameter nearly 4 times larger. To the best of our knowledge, this is the first observation of the growth of a fully developed, very stable SPR-like band for a gold nanocluster of such dimensions. The robust polylysine protective shell makes the nanoparticles very stable under conditions of chemical etching, in the presence of glutathione, and at different pH values, without gold core deshielding or alteration of the SPR-like band. This polymerization method can conceivably be extended to prepare core–shell nanosystems based on other mono- or co-poly(amino acids).
Pub.: 02 Feb '17, Pinned: 28 Jun '17
Abstract: The self-assembling morphologies of low-concentration (mostly 1 and 10mg/mL) bicellar mixtures composed of zwitterionic dipalmitoyl (di-C16) phosphatidylcholine (DPPC), dihexanoyl (di-C6) phosphatidylcholine (DHPC), and negatively charged dipalmitoyl (di-C16) phosphatidylglycerol (DPPG) were investigated using small angle neutron scattering, dynamic light scattering and transmission electron microscopy. A polyethylene glycol conjugated (PEGylated) lipid, distearoyl phosphoethanolamine-[methoxy (polyethyleneglycol)-2000] (PEG2000-DSPE), was incorporated in the system at 5mol% of the total lipid composition. The effects of several parameters on the spontaneous structures were studied, including temperature, lipid concentration, salinity, and PEG2000-DSPE. In general, nanodiscs (bicelles) were observed at low temperatures (below the melting temperature, TM of DPPC) depending on the salinity of the solutions. Nanodisc-to-vesicle transition was found upon the elevation of temperature (above TM) in the cases of low lipid concentration in the absence of PEG2000-DSPE or high salinity. Both addition of PEG2000-DSPE and high lipid concentration stabilize the nanodiscs, preventing the formation of multilamellar vesicles, while high salinity promotes vesiculation and the formation of aggregation. This study suggests that the stability of such nanodiscs is presumably controlled by the electrostatic interactions, the steric effect induced by PEG2000-DSPE, and the amount of DHPC located at the disc rim.
Pub.: 25 Feb '14, Pinned: 28 Jun '17
Abstract: Lipid-based nanodiscs (bicelles) are able to form in mixtures of long- and short-chain lipids. Initially, they are of uniform size but grow upon dilution. Previously, nanodisc growth kinetics have been studied using time-resolved small angle neutron scattering (SANS), a technique which is not well suited for probing their change in size immediately after dilution. To address this, we have used dynamic light scattering (DLS), a technique which permits the collection of useful data in a short span of time after dilution of the system. The DLS data indicate that the negatively charged lipids in nanodiscs play a significant role in disc stability and growth. Specifically, the charged lipids are most likely drawn out from the nanodiscs into solution, thereby reducing interparticle repulsion and enabling the discs to grow. We describe a population balance model, which takes into account Coulombic interactions and adequately predicts the initial growth of nanodiscs with a single parameter - i.e., surface potential. The results presented here strongly support the notion that the disc coalescence rate strongly depends on nanoparticle charge density. The present system containing low-polydispersity lipid nanodiscs serves as a good model for understanding how charged discoidal micelles coalesce.
Pub.: 03 Apr '14, Pinned: 28 Jun '17
Abstract: We have designed and constructed a temperature-controllable shear flow cell for in-situ study on flow alignable systems. The device has been tested in the neutron diffraction and has the potential to be applied in the small angle neutron scattering configuration to characterize the nanostructures of the materials under flow. The required sample amount is as small as 1 ml. The shear rate on the sample is controlled by the flow rate produced by an external pump and can potentially vary from 0.11 to 3.8 × 10(5) s(-1). Both unidirectional and oscillational flows are achievable by the setting of the pump. The instrument is validated by using a lipid bicellar mixture, which yields non-alignable nanodisc-like bicelles at low T and shear-alignable membranes at high T. Using the shear cell, the bicellar membranes can be aligned at 31 °C under the flow with a shear rate of 11.11 s(-1). Multiple high-order Bragg peaks are observed and the full width at half maximum of the "rocking curve" around the Bragg's condition is found to be 3.5°-4.1°. It is noteworthy that a portion of the membranes remains aligned even after the flow stops. Detailed and comprehensive intensity correction for the rocking curve has been derived based on the finite rectangular sample geometry and the absorption of the neutrons as a function of sample angle [See supplementary material at http://dx.doi.org/10.1063/1.4908165 for the detailed derivation of the absorption correction]. The device offers a new capability to study the conformational or orientational anisotropy of the solvated macromolecules or aggregates induced by the hydrodynamic interaction in a flow field.
Pub.: 03 Mar '15, Pinned: 28 Jun '17